Quantum Sensing of Free Radical Generation in Mitochondria of Human Keratinocytes during UVB Exposure.

Ultraviolet (UV) radiation is known to cause skin issues, such as dryness, aging, and even cancer. Among UV rays, UVB stands out for its ability to trigger problems within cells, including mitochondrial dysfunction, oxidative stress, and DNA damage. Free radicals are implicated in these cellular responses, but they are challenging to measure due to their short lifetime and limited diffusion range. In our study, we used a quantum sensing technique (T1 relaxometry) involving fluorescent nanodiamonds (FNDs) that change their optical properties in response to magnetic noise. This allowed us to monitor the free radical presence in real time. To measure radicals near mitochondria, we coated FNDs with antibodies, targeting mitochondrial protein voltage-dependent anion channel 2 (anti-VDAC2). Our findings revealed a dynamic rise in radical levels on the mitochondrial membrane as cells were exposed to UVB (3 J/cm2), with a significant increase observed after 17 min.

Anti-Photodamage Effect of Agaricus blazei Murill Polysaccharide on UVB-Damaged HaCaT Cells.

UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Agaricus blazei Murill (ABM) is an edible medicinal and nutritional fungus. One of its constituents, Agaricus blazei Murill polysaccharide (ABP), has been reported to exhibit antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, which suggests potential effects that protect against photodamage. In this study, a UVB-induced photodamage HaCaT model was established to investigate the potential reparative effects of ABP and its two constituents (A1 and A2). Firstly, two purified polysaccharides, A1 and A2, were obtained by DEAE-52 cellulose column chromatography, and their physical properties and chemical structures were studied. A1 and A2 exhibited a network-like microstructure, with molecular weights of 1.5 × 104 Da and 6.5 × 104 Da, respectively. The effects of A1 and A2 on cell proliferation, the mitochondrial membrane potential, and inflammatory factors were also explored. The results show that A1 and A2 significantly promoted cell proliferation, enhanced the mitochondrial membrane potential, suppressed the expression of inflammatory factors interleukin-1ß (IL-1ß), interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and increased the relative content of filaggrin (FLG) and aquaporin-3 (AQP3). The down-regulated JAK-STAT signaling pathway was found to play a role in the response to photodamage. These findings underscore the potential of ABP to ameliorate UVB-induced skin damage.

Germicidal lamps using UV-C radiation may pose health safety issues: a biomolecular analysis of their effects on apoptosis and senescence.

The battle against the COVID-19 pandemic has spurred a heightened state of vigilance in global healthcare, leading to the proliferation of diverse sanitization methods. Among these approaches, germicidal lamps utilizing ultraviolet (UV) rays, particularly UV-C (wavelength ranging from 280 to 100 nm), have gained prominence for domestic use. These light-emitting diode (LED) lamps are designed to sanitize the air, objects, and surfaces. However, the prevailing concern is that these UV lamps are often introduced into the market without adequate accompanying information to ensure their safe utilization. Importantly, exposure to absorbed UV light can potentially trigger adverse biological responses, encompassing cell death and senescence. Our research encompassed a series of investigations aimed at comprehending the biological repercussions of UV-C radiation exposure from readily available domestic lamps. Our focus centered on epithelial retinal cells, keratinocytes, and fibroblasts, components of the skin and ocular targets frequently exposed to UV irradiation. Our findings underscore the potential harm associated with even brief exposure to UV, leading to irreversible and detrimental alterations in both skin cells and retinal cells of the eye. Notably, epithelial retinal cells exhibited heightened sensitivity, marked by substantial apoptosis. In contrast, keratinocytes demonstrated resilience to apoptosis even at elevated UV doses, though they were prone to senescence. Meanwhile, fibroblasts displayed a gradual amplification of both senescence and apoptosis as radiation doses escalated. In summary, despite the potential benefits offered by UV-C in deactivating pathogens like SARS-CoV-2, it remains evident that the concurrent risks posed by UV-C to human health cannot be ignored.

Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

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.

A recombinant plasmid encoding human hepatocyte growth factor promotes healing of combined radiation-trauma skin injury involved in regulating Nrf2 pathway in mice.

Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro, and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1ß and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic.

Ferulic acid in synergy with retinol alleviates oxidative injury of HaCaT cells during UVB-induced photoaging.

Application of retinol (Vitamin A, VA) in skincare is limited for instability, poor water solubility, and skin intolerance that combats skin aging. We employed computer-aided virtual screening and cell experiments with transcriptomics, thereby unveiling the comprehensive gene expression and regulation pathway of photoaging HaCaT cell treated with ferulic acid (FA) in synergizing with VA. Through network pharmacology analysis, the combined use of VA and FA exhibited highly correlated cross-targets with skin aging acting on EGFR, PTPN1, ESR2, GSK3B, BACE1, PYGL, PTGS2 and APP. The indicators of oxidative stress, such as SOD, GSH, MDA, CAT and ROS in HaCaT cells after co-administration, were significantly improved from those in photoaging group (p<0.0001). 155 differential expressed genes (DEGs) were specific between groups, while reducing the expression of PTGS2 was identified as an important regulatory factor in photoaging HaCaT cells by VA and FA. Those DEGs of co-administration group focused on oxidative-reduction enzyme activity, skin growth, keratinization, and steroid biosynthesis. Apparently, the co-administration of VA and FA effectively mitigated the process of UVB-induced photoaging by reducing oxidative stress injury, inflammation responses, and regulating cell growth. This synergistic approach significantly slowed down the photoaging progression and improved the applied performance of VA in HaCaT cells.

Photodegradation enhances the toxic effect of anthracene on skin.

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.

Water-filtered infrared A irradiation exerts antifungal effects on the skin fungus Malassezia.

Many common skin diseases are associated with changes in the microbiota. This applies for the commensal yeast Malassezia, which is linked to a wide range of skin disorders ranging from mild dandruff to severe seborrheic and atopic dermatitis, all of which have a detrimental impact on the individuals' quality of life. While antifungal medications offer relief in many cases, the challenges of disease recurrence and the emergence of resistance to the limited range of available antifungal drugs poses a pressing need for innovative therapeutic options. Here we examined the activity of water-filtered infrared A (wIRA) irradiation against Malassezia. wIRA's antimicrobial and wound healing properties make it an attractive option for localized, non-invasive, and contact-free treatment of superficial skin infections. Irradiation of Malassezia furfur with wIRA (570-1400 nm) resulted in a reduction of the yeast's metabolic activity. When put in contact with immune cells, wIRA-irradiated M. furfur was recovered at lower counts than non-irradiated M. furfur. Likewise, wIRA irradiation of M. furfur put in contact with keratinocytes, the primary host interface of the fungus in the skin, reduced the fungal counts, while the keratinocytes were not affected by the irradiation. The combination of wIRA with the photosensitizer methyl aminolevulinate exerted an additional antifungal effect on M. furfur, irrespective of the presence or absence of keratinocytes, suggesting an enhancement of the treatment effect when used in combination. These findings suggest that wIRA holds promise as a potential therapy for skin disorders associated with Malassezia.

Interferon alpha promotes caspase-8 dependent ultraviolet light-mediated keratinocyte apoptosis via interferon regulatory factor 1.

Introduction: Ultraviolet (UV) light is a known trigger of both cutaneous and systemic disease manifestations in lupus patients. Lupus skin has elevated expression of type I interferons (IFNs) that promote increased keratinocyte (KC) death after UV exposure. The mechanisms by which KC cell death is increased by type I IFNs are unknown. Methods: Here, we examine the specific cell death pathways that are activated in KCs by type I IFN priming and UVB exposure using a variety of pharmacological and genetic approaches. Mice that overexpress Ifnk in the epidermis were exposed to UVB light and cell death was measured. RNA-sequencing from IFN-treated KCs was analyzed to identify candidate genes for further analysis that could drive enhanced cell death responses after UVB exposure. Results: We identify enhanced activation of caspase-8 dependent apoptosis, but not other cell death pathways, in type I IFN and UVB-exposed KCs. In vivo, overexpression of epidermal Ifnk resulted in increased apoptosis in murine skin after UVB treatment. This increase in KC apoptosis was not dependent on known death ligands but rather dependent on type I IFN-upregulation of interferon regulatory factor 1 (IRF1). Discussion: These data suggest that enhanced sensitivity to UV light exhibited by lupus patients results from type I IFN priming of KCs that drives IRF1 expression resulting in caspase-8 activation and increased apoptosis after minimal exposures to UVB.

Antiviral and synergistic effects of photo-energy with acyclovir on herpes simplex virus type 1 infection.

This experimental study aimed to evaluate the antiviral and synergistic effects of photoenergy irradiation on human herpes simplex virus type I (HSV-1) infection. We assessed viral replication, plaque formation, and relevant viral gene expression to examine the antiviral and synergistic effects of blue light (BL) with acyclovir treatment. Our results showed that daily BL (10 J/cm2) irradiation inhibited plaque-forming ability and decreased viral copy numbers in HSV-1-infected monkey kidney epithelial Vero cells and primary human oral keratinocyte (HOK) cells. Combined treatment with the antiviral agent acyclovir and BL irradiation increased anti-viral activity, reducing viral titers and copy numbers. In particular, accumulated BL irradiation suppressed characteristic viral genes including UL19 and US6, and viral DNA replication-essential genes including UL9, UL30, UL42, and UL52 in HOK cells. Our results suggest that BL irradiation has anti-viral and synergistic properties, making it a promising therapeutic candidate for suppressing viral infections in clinical trials.

Salvianolic acid A prevents UV-induced skin damage by inhibiting the cGAS-STING pathway.

DNA damage resulting from UV irradiation on the skin has been extensively documented in numerous studies. In our prior investigations, we demonstrated that UVB-induced DNA breakage from keratinocytes can activate the cGAS-STING pathway in macrophages. The cGAS-STING signaling pathway serves as the principal effector for detecting and responding to abnormal double-stranded DNA in the cytoplasm. Expanding on our previous findings, we have further validated that STING knockout significantly diminishes UVB-induced skin damage, emphasizing the critical role of cGAS-STING activation in this context. Salvianolic acid A, a principal active constituent of Salvia miltiorrhiza Burge, has been extensively studied for its therapeutic effects in conditions such as coronary heart disease, angina pectoris, and diabetic peripheral neuropathy. However, its effect on cGAS-STING pathway and its ability to alleviate skin damage have not been previously reported. In a co-culture system, supernatant from UVB-treated keratinocytes induced IRF3 activation in macrophages, and this activation was inhibited by salvianolic acid A. Our investigation, employing photodamage and photoaging models, establishes that salvianolic acid A effectively mitigates UV-induced epidermal thickening and collagen degeneration. Treatment with salvianolic acid A significantly reduced skin damage, epidermal thickness increase, and keratinocyte hyperproliferation compared to the untreated photo-damage and photoaging model groups. In summary, salvianolic acid A emerges as a promising candidate for preventing UV-induced skin damage by inhibiting cGAS-STING activation. This research enhances our understanding of the intricate mechanisms underlying skin photodamage and provides a potential avenue for the development of therapeutic interventions.

Alternative autophagy dampens UVB-induced NLRP3 inflammasome activation in human keratinocytes.

Sunlight exposure results in an inflammatory reaction of the skin commonly known as sunburn, which increases skin cancer risk. In particular, the ultraviolet B (UVB) component of sunlight induces inflammasome activation in keratinocytes to instigate the cutaneous inflammatory responses. Here, we explore the intracellular machinery that maintains skin homeostasis by suppressing UVB-induced inflammasome activation in human keratinocytes. We found that pharmacological inhibition of autophagy promoted UVB-induced NLRP3 inflammasome activation. Unexpectedly, however, gene silencing of Atg5 or Atg7, which are critical for conventional autophagy, had no effect, whereas gene silencing of Beclin1, which is essential not only for conventional autophagy but also for Atg5/Atg7-independent alternative autophagy, promoted UVB-induced inflammasome activation, indicating an involvement of alternative autophagy. We found that damaged mitochondria were highly accumulated in UVB-irradiated keratinocytes when alternative autophagy was inhibited, and they appear to be recognized by NLRP3. Overall, our findings indicate that alternative autophagy, rather than conventional autophagy, suppresses UVB-induced NLRP3 inflammasome activation through the clearance of damaged mitochondria in human keratinocytes and illustrate a previously unknown involvement of alternative autophagy in inflammation. Alternative autophagy may be a new therapeutic target for sunburn and associated cutaneous disorders.

KTN1 mediated unfolded protein response protects keratinocytes from ionizing radiation-induced DNA damage.

BACKGROUND: The unfolded protein response (UPR) is one of the cytoprotective mechanisms against various stresses and essential for the normal function of skin. Skin injury caused by ionizing radiation (IR) is a common side effect of radiotherapy and it is unclear how UPR affects IR-induced skin injury. OBJECTIVES: To verify the effect of UPR on IR-induced DNA damage in keratinocytes and the relation between an endoplasmic reticulum (ER) protein KTN1 and UPR. METHODS: All experiments were performed on keratinocytes models: HaCaT and HEK-A. ER lumen and the expression levels of KTN1 and UPR pathway proteins (PERK, IRE1α and ATF6) were examined by transmission electron microscopy and immunoblotting, respectively. 4-PBA, an UPR inhibitor, was used to detected its effects on DNA damage and cell proliferation. Subsequently, the effects of KTN1 deletion on UPR, DNA damage and cell proliferation after IR were detected. Tunicamycin was used to reactivate UPR and then we examined its effects on DNA damage. RESULTS: UPR was activated by IR in keratinocytes. Inhibition of UPR aggravated DNA damage and suppressed cell proliferation after IR. KTN1 expression was upregulated by IR and KTN1 depletion reduced ER expansion and the expression of UPR-related proteins. Moreover, KTN1 depletion aggravated DNA damage and suppressed cell proliferation after IR could reversed by reactivation of UPR. CONCLUSION: KTN1 deletion aggravates IR-induced keratinocyte DNA damage via inhibiting UPR. Our findings provide new insights into the mechanisms of keratinocytes in response to IR-induced damage.

Photoreactivity of polycyclic aromatic hydrocarbons (PAHs) and their mechanisms of phototoxicity against human immortalized keratinocytes (HaCaT).

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds in the environment. They are produced by many anthropogenic sources of different origins and are known for their toxicity, carcinogenicity, and mutagenicity. Sixteen PAHs have been identified as Priority Pollutants by the US EPA, which are often associated with particulate matter, facilitating their dispersion through air and water. When human skin is exposed to PAHs, it might occur simultaneously with solar radiation, potentially leading to phototoxic effects. Phototoxic mechanisms involve the generation of singlet oxygen and reactive oxygen species, DNA damage under specific light wavelengths, and the formation of charge transfer complexes. Despite predictions of phototoxic properties for some PAHs, there remains a paucity of experimental data. This study examined the photoreactive and phototoxic properties of the 16 PAHs enlisted in the Priority Pollutants list. Examined PAHs efficiently photogenerated singlet oxygen and superoxide anion in simple solutions. Furthermore, singlet oxygen phosphorescence was detected in PAH-loaded HaCaT cells. Phototoxicity against human keratinocytes was evaluated using various assays. At 5 nM concentration, examined PAHs significantly reduced viability and mitochondrial membrane potential of HaCaT cells following the exposure to solar simulated light. Analyzed compounds induced a substantial peroxidation of cellular proteins after light treatment. The results revealed that a majority of the examined PAHs exhibited substantial reactive oxygen species photoproduction under UVA and violet-blue light, with their phototoxicity corresponding to their photoreactive properties. These findings improve our comprehension of the interactions between PAHs and human skin cells under environmental conditions, particularly when exposed to solar radiation.

Vitiligo non-responding lesions to narrow band UVB have intriguing cellular and molecular abnormalities that may prevent epidermal repigmentation.

We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. Using immunostaining studies, discovery-stage RNA-Seq analysis, and confirmatory in situ hybridization, we analyzed paired biopsies collected from vitiligo lesions that did not repigment after 6 months of NBUVB treatment (non-responding) and compared them with repigmented (responding) lesions from the same patient. Non-responding lesions exhibited acanthotic epidermis, had low number of total, proliferative, and differentiated melanocyte (MC) populations, and increased number of senescent keratinocytes (KCs) and of cytotoxic CD8+ T cells as compared with responding lesions. The abnormal response in the non-responding lesions was driven by a dysregulated cAMP pathway and of upstream activator PDE4B, and of WNT/ß-catenin repigmentation pathway. Vitiligo-responding lesions expressed high levels of WNT10B ligand, a molecule that may prevent epidermal senescence induced by NBUVB, and that in cultured melanoblasts prevented the pro-melanogenic effect of α-MSH. Understanding the pathways that govern lack of NBUVB-induced vitiligo repigmentation has a great promise in guiding the development of new therapeutic strategies for vitiligo.

Comparison of cellular responses to ionizing radiation in keratinocytes isolated from healthy donors and type II diabetes patients.

PURPOSE: Due to the expanding repertoire of treatment devices that use radiation, the possibility of exposure to both low-dose and high-dose radiation continues to increase. Skin is the outermost part of the body and thus directly exposed to radiation-induced damage. In particular, the skin of diabetes patients is fragile and easily damaged by external stimuli, such as radiation. However, damage and cellular responses induced by ionizing irradiation in diabetic skin have not been explored in detail. In this study, we investigated the effects of several irradiation dose on normal keratinocytes and those from type II diabetes patients, with particular focus on DNA damage. MATERIALS AND METHODS: Cellular responses to low-dose radiation (0.1 Gy) and high-dose radiation (0.5 and 2 Gy) were evaluated. Cell cycle analysis was conducted via flow cytometry and cell viability analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Proteins related to the DNA damage response (DDR) and repair signaling pathways and apoptosis were detected via immunoblot analysis. Apoptosis and cell differentiation were additionally examined in 3D skin organoids using immunohistochemistry. RESULTS: Compared to respective control groups, no significant changes were observed in cell cycle, DDR and repair mechanisms, cell survival, and differentiation in response to 0.1 Gy irradiation in both normal and diabetes type II keratinocytes. On the other hand, the cell cycle showed an increase in the G2/M phase in both cell types following exposure to 2 Gy irradiation. At radiation doses 2 Gy, activation of the DDR and repair signaling pathways, apoptosis, and cell differentiation were increased and viability was decreased in both cell types. Notably, these differences were more pronounced in normal than diabetes type II keratinocytes. CONCLUSIONS: Normal keratinocytes respond more strongly to radiation-induced damage and recovery than diabetes type II keratinocytes.

Naringin acts as a TRPV1 antagonist to attenuate UVB-induced senescence and damage in HaCaT cells.

This study aimed to explore the mechanism of naringin (Nar) in alleviating ultraviolet B (UVB)-induced HaCaT cell senescence and damage. Human keratinocytes (HaCaT cells) were divided into control, UVB, UVB + Nar, UVB + Cap, and UVB + Nar + Cap groups. Analysis was performed using the MTT assay to assess cell viability, flow cytometry to measure the apoptosis level, SA-ß-Gal staining to observe cellular senescence, and Western blot to assess protein levels of TRPV1, p16, p53, p21, matrix metalloproteinase (MMP)-1, and MMP-9. Both UVB irradiation and capsaicin (Cap) treatment upregulated the expression of TRPV1 in HaCaT cells, inhibited cell proliferation, promoted apoptosis, and increased the expression of p16, p53, p21, MMP-1, and MMP-9. Nar treatment reversed the above effects via inhibition of TRPV1 expression, thereby relieving senescence and cell damage induced by UVB irradiation. Taken together, these findings suggest that Nar can reduce UVB-induced senescence and damage in HaCaT cells by acting as an antagonist of TRPV1.

Astaxanthin Synergizes with Ionizing Radiation (IR) in Oral Squamous Cell Carcinoma (OSCC).

Astaxanthin (ATX) is known for its antioxidant and anti-inflammation functions yet its role in cancers requires more research. This study is aimed to reveal the potential synergetic effect of ATX with ionizing radiation (IR) in OSCC. Cell survival was measured after human OSCC cells including CAL27 and SCC9, and normal human oral keratinocytes (NHOKs) were treated with different concentrations of ATX for 24 h. Colony formation assays were performed after OSCC cells were treated with IR, ATX (20 µ M), or combined and survival fraction was analyzed. Malondialdehyde (MDA), glutathione (GSH), and intercellular iron levels were measured. Western blot method was used to measure the ferroptosis-related proteins, GPX4, SLC7A11, and ACSL4. In xenograft mice model, we evaluated the tumor volumes, tumor growth, and examined the GPX4/ACSL4 proteins in tumor tissues using Immunohistochemistry (IHC). ATX inhibited viability of OSCC cells but not NHOK. In OSCC cells, ATX further enhanced the cell death induced by IR. In addition, ATX promoted the MDA content, Iron levels but inhibited the GSH regulated by IR in cells. ATX could synergize with IR, further inhibiting GPX4, SLC7A11 and promoting ACSL4 in OSCC cells. In vivo, ATX and IR treatment inhibited OSCC tumor growth and the group with combined treatment showed the most inhibitory effect. GPX4 was inhibited by IR and further inhibited in the combined group while ACSL4 was promoted by IR and enhanced more significantly in the combined group. ATX might synergize with IR treatment in OSCC partly via ferroptosis.

Q-switched Nd:YAG laser protects human keratinocytes from oxidative stress and inflammation via AhR-Nrf2 pathway.

In recent years, some treatments for esthetic and pathologic skin conditions have increasingly been based on the use of non-ablative neodymium-doped yttrium aluminum garnet (Nd:YAG) laser due to its greater penetration ability than other types of lasers, few contraindications, minimal side effects, no damage for epidermidis and the rapid recovery of the treated patients. The skin is frequently exposed to many stressors such as radiation, toxic substances, metabolites, foods, mechanical insults, and allergen exposition that cause oxidative damage and have a decisive influence on the aging process. The imbalance between reactive oxygen species, reactive nitrogen species, and the malfunctioning of the antioxidant defense system promotes the establishment of an excessive inflammatory process, which can induce various diseases including cancer and neurodegenerative disorders. The present study investigated the cytoprotective function of Q-switched Nd:YAG laser against stress aging and cell injury in HaCaT cells. We evaluated the effect of the laser on antioxidant defenses, inflammation, metalloproteinases' expression, and the AhR-Nrf2 pathway. Q-switched Nd:YAG is able to upregulate the AhR pathway and the expression of IL-6 and TGF-ß, which are involved in wound repair process, and to downregulate the expression of MMP-2 and 9, so preventing the collagen degradation. Q-switched Nd:YAG can stimulate the cellular antioxidant defenses by activating the AhR-Nrf2 system.

Influence of UV nail lamps radiation on human keratinocytes viability.

Ultraviolet nail lamps are becoming increasingly popular, however, the safety of their use remains controversial. The following article directly responds to recently published literature data and aims to determine the viability of human keratinocytes irradiated by a UV nail-drying machine. Cells were exposed to 365-405 nm wavelength UV light emitted by a nail drying machine in two time variants: 4 and 20 min, with and without sunscreen cream SPF50 protection, and compared to the untreated control. Compared to the control, cell viability after irradiation for 4 min decreased insignificantly (p < 0.1), however for 20 min decreased by 35% (p < 0.0001). Furthermore, cells with sunscreen protection compared to those without showed significantly increased viability, regardless of time-variant (p < 0.0001). The study shows that 4-min irradiation does not significantly reduce the viability of human keratinocytes and the time of 20 min significantly alters the research results compared to 4 min, which corresponds to real conditions. The results suggest that typical manicure exposure time does not significantly affect keratinocyte viability, which could increase the risk of developing skin cancers. Despite the above results, it is recommended to use sunscreen protection on your hands during the procedure, which significantly increases the viability of keratinocytes during ultraviolet nail lamp radiation.