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The Journal of Investigative Dermatology Jun 2024The incidence and distribution of cutaneous melanoma differs between the sexes, but it is unclear whether these differences have been constant through time or across...
The incidence and distribution of cutaneous melanoma differs between the sexes, but it is unclear whether these differences have been constant through time or across generations. We compared incidence trends by age, sex, and anatomic site by analyzing long-term melanoma data (1982-2018) in three populations residing at high-, moderate- and low- ambient sun exposure: Queensland, Australia; United States White; Scotland. We fit age-period-cohort models and compared trends in the male-to-female incidence rate ratio (IRR) by site and sex. In men, melanoma incidence was always highest on the trunk; in women, incidence was historically highest on limbs, but there have been recent increases in truncal melanoma among females in all populations. The IRR showed excess melanoma in females on the lower limb in most age groups in all populations. In contrast, there was a male excess of melanoma on the trunk (from about age 25 years) and head/neck (from about age 40 years) which increased with age. Birth cohort analyses identified 'turning points' in incidence from high to low incidence among recent birth cohorts, which differed by population and site. Changing exposure to UV radiation is implicated, possibly superimposed upon innate differences between the sexes in site-specific susceptibility.
PubMed: 38897542
DOI: 10.1016/j.jid.2024.05.011 -
Environmental Health Perspectives Jun 2024Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although...
BACKGROUND
Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear.
OBJECTIVES
We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd.
METHODS
Male wild-type (WT), global -knockout () and myeloid-specific knockout [(M)-KO] mice were administered Cd (50 or ) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or ) with a combination of genetic and chemical modulations targeting NRF2 and NRF1.
RESULTS
Compared with relevant control mice, global or (M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to Cd in drinking water for up to 16 wk. osteoclastogenic analyses suggested that -deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to ) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the deficiency-worsened and Cd-provoked osteoclastogenesis. L- silenced (via lentiviral means) -knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of -KD alone exposed to Cd, suggesting a mitigating effect of the silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants -acetyl-l-cysteine () and mitoquinone mesylate (MitoQ; ) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed -KD cells.
CONCLUSIONS
This and study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849.
Topics: Animals; Mice; Male; Cadmium; NF-E2-Related Factor 2; Osteoclasts; Osteogenesis; Mice, Knockout; NF-E2-Related Factor 1; Mice, Inbred C57BL; Cell Differentiation
PubMed: 38896780
DOI: 10.1289/EHP13849 -
BioRxiv : the Preprint Server For... Jun 2024Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. Tanning bed radiation is often...
BACKGROUND
Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. Tanning bed radiation is often thought of as a substitute for natural UV radiation despite differences in the maximum doses, UV content, body sites exposed, and patterns of melanoma that arise.
METHODS
To better understand the epidemiologic trends and etiology of melanoma associated with tanning bed use, we described the patterns of melanoma in patients with quantifiable tanning bed usage and performed exome sequencing of 182 melanocytes from normal skin of a subset of these patients.
RESULTS
Tanning bed users were more likely than non-users to have melanoma on body sites with low cumulative levels of sun damage and were more likely to have multiple melanomas. The melanocytes in normal appearing skin from tanning bed users had higher mutation burdens, a higher proportion of melanocytes with pathogenic mutations, and distinct mutational signatures. These differences were most prominent over body sites that experience comparatively less exposure to natural sunlight.
CONCLUSIONS
We conclude that tanning bed radiation induces melanoma by increasing the mutation burden of melanocytes and by mutagenizing a broader field of melanocytes than are typically exposed to natural sunlight. The unique signatures of mutations in skin cells of tanning users may be attributable to the distinct spectra of radiation emitted from solariums.
PubMed: 38895302
DOI: 10.1101/2024.06.04.597225 -
Sensors (Basel, Switzerland) May 2024The aim was to evaluate and optimize the performance of sensor monitors in measuring PM and PM under typical emission scenarios both indoors and outdoors.
OBJECTIVE
The aim was to evaluate and optimize the performance of sensor monitors in measuring PM and PM under typical emission scenarios both indoors and outdoors.
METHOD
Parallel measurements and comparisons of PM and PM were carried out between sensor monitors and standard instruments in typical indoor (2 months) and outdoor environments (1 year) in Shanghai, respectively. The optimized validation model was determined by comparing six machining learning models, adjusting for meteorological and related factors. The intra- and inter-device variation, measurement accuracy, and stability of sensor monitors were calculated and compared before and after validation.
RESULTS
Indoor particles were measured in a range of 0.8-370.7 μg/m and 1.9-465.2 μg/m for PM and PM, respectively, while the outdoor ones were in the ranges of 1.0-211.0 μg/m and 0.0-493.0 μg/m, correspondingly. Compared to machine learning models including multivariate linear model (ML), K-nearest neighbor model (KNN), support vector machine model (SVM), decision tree model (DT), and neural network model (MLP), the random forest (RF) model showed the best validation after adjusting for temperature, relative humidity (RH), PM/PM ratios, and measurement time lengths (months) for both PM and PM, in indoor (R: 0.97 and 0.91, root-mean-square error (RMSE) of 1.91 μg/m and 4.56 μg/m, respectively) and outdoor environments (R: 0.90 and 0.80, RMSE of 5.61 μg/m and 17.54 μg/m, respectively), respectively.
CONCLUSIONS
Sensor monitors could provide reliable measurements of PM and PM with high accuracy and acceptable inter and intra-device consistency under typical indoor and outdoor scenarios after validation by RF model. Adjusting for both climate factors and the ratio of PM/PM could improve the validation performance.
PubMed: 38894239
DOI: 10.3390/s24113448 -
Molecules (Basel, Switzerland) Jun 2024Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics, chamazulene is exploited as a natural coloring and soothing agent....
Chamazulene (CA) is an intensely blue molecule with a wealth of biological properties. In cosmetics, chamazulene is exploited as a natural coloring and soothing agent. CA is unstable and tends to spontaneously degrade, accelerated by light. We studied the photodegradation of CA upon controlled exposure to UVB-UVA irradiation by multiple techniques, including GC-MS, UHPLC-PDA-ESI-MS/MS and by direct infusion in ESI-MS, which were matched to in silico mass spectral simulations to identify degradation products. Seven byproducts formed upon UVA exposure for 3 h at 70 mW/cm (blue-to-green color change) were identified, including CA dimers and CA benzenoid, which were not found on extended 6 h irradiation (green-to-yellow fading). Photostability tests with reduced irradiance conducted in various solvents in the presence/absence of air indicated highest degradation in acetonitrile in the presence of oxygen, suggesting a photo-oxidative mechanism. Testing in the presence of antioxidants (tocopherol, ascorbyl palmitate, hydroxytyrosol, bakuchiol, γ-terpinene, TEMPO and their combinations) indicated the highest protection by tocopherol and TEMPO. Sunscreens ethylhexyl methoxycinnamate and particularly Tinosorb S (but not octocrylene) showed good CA photoprotection. Thermal stability tests indicated no degradation of CA in acetonitrile at 50 °C in the dark for 50 days; however, accelerated degradation occurred in the presence of ascorbyl palmitate.
Topics: Azulenes; Oils, Volatile; Oxidation-Reduction; Photolysis; Ultraviolet Rays; Antioxidants; Achillea; Artemisia; Tandem Mass Spectrometry; Gas Chromatography-Mass Spectrometry
PubMed: 38893479
DOI: 10.3390/molecules29112604 -
Journal of Clinical Medicine Jun 2024The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally...
The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally invasive treatment alternatives. Traditional surgical approaches, while effective, often result in notable cosmetic and functional limitations, particularly for lesions located on the face. This study explores High-Intensity Focused Ultrasound (HIFU) as a promising, non-invasive treatment option that aims to overcome these challenges, potentially revolutionizing BCC treatment by offering a balance between efficacy and cosmetic outcomes. Our investigation enrolled 8 patients, presenting a total of 15 BCC lesions, treated with a 20 MHz HIFU device. The selection of treatment parameters was precise, utilizing probe depths from 0.8 mm to 2.3 mm and energy settings ranging from 0.7 to 1.3 Joules (J) per pulse, determined by the lesion's infiltration depth as assessed via pre-procedure ultrasonography. A key component of our methodology included dermatoscopic monitoring, which allowed for detailed observation of the lesions' response to treatment over time. Patient-reported outcomes and satisfaction levels were systematically recorded, providing insights into the comparative advantages of HIFU. Initial responses after HIFU treatment included whitening and edema, indicative of successful lesion ablation. Early post-treatment observations revealed minimal discomfort and quick recovery, with crust formation resolving within two weeks for most lesions. Over a period of three to six months, patients reported significant improvement, with lesions becoming lighter and blending into the surrounding skin, demonstrating effective and aesthetically pleasing outcomes. Patient satisfaction surveys conducted six months post-treatment revealed high levels of satisfaction, with 75% of participants reporting very high satisfaction due to minimal scarring and the non-invasive nature of the procedure. No recurrences of BCC were noted, attesting to the efficacy of HIFU as a treatment option. The findings from this study confirm that based on dermoscopy analysis, HIFU is a highly effective and patient-preferred non-invasive treatment modality for Basal Cell Carcinoma. HIFU offers a promising alternative to traditional surgical and non-surgical treatments, reducing the cosmetic and functional repercussions associated with BCC management. Given its efficacy, safety, and favorable patient satisfaction scores, HIFU warrants further investigation and consideration for broader clinical application in the treatment of BCC, potentially setting a new standard in dermatologic oncology care. This work represents a pilot study that is the first to describe the use of HIFU in the treatment of BCC.
PubMed: 38892988
DOI: 10.3390/jcm13113277 -
Nutrients May 2024Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This...
Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This cross-sectional study, conducted from May 2022 to December 2023 in Timisoara, Romania, aimed to evaluate the potential influence of vitamin D supplementation on the incidence of respiratory infections among preschool-age children. This study examined 215 children over 18 months who were split into a group of patients with recurrent respiratory infections ( = 141) and another group of patients with only one respiratory tract infection in the past 12 months ( = 74). Patients were evaluated based on their serum vitamin D levels 25(OH)D, demographic characteristics, and health outcomes. The study identified that preschool-age children with recurrent infections had significantly lower mean vitamin D concentrations (24.5 ng/mL) compared to the control group (29.7 ng/mL, < 0.001). Additionally, a higher proportion of vitamin D deficiency was observed among children with recurrent infections in the past 12 months. Notably, vitamin D supplementation above 600 IU/week significantly reduced the likelihood of respiratory infections, evidenced by an odds ratio of 0.523 ( < 0.001), indicating that preschool-age children receiving a dose of vitamin D higher than 600 IU/week were about half as likely to experience respiratory infections compared to those who did not. Furthermore, no significant associations were found between sun exposure, daily sunscreen use, and the incidence of respiratory infections. Conclusively, this study underscores the potential role of vitamin D in helping the immune system against respiratory infections in preschool-age children. The observed protective effect of vitamin D supplementation suggests a potential public health strategy to mitigate the incidence of respiratory infections in preschool children on top of the already known benefits.
Topics: Humans; Respiratory Tract Infections; Child, Preschool; Vitamin D; Cross-Sectional Studies; Male; Female; Vitamin D Deficiency; Dietary Supplements; Incidence; Romania; Infant; Recurrence
PubMed: 38892528
DOI: 10.3390/nu16111595 -
International Journal of Molecular... May 2024Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells' clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR),...
Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells' clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation.
Topics: Humans; Oxidative Stress; DNA Damage; Cell Differentiation; Skin Neoplasms; Inflammation; Male; Female; Middle Aged; Ultraviolet Rays; Aged; Keratinocytes; Nitric Oxide Synthase Type II; Adult; Tumor Suppressor Protein p53; Skin; Ki-67 Antigen; Cyclin-Dependent Kinase Inhibitor p16; Interleukin-6
PubMed: 38891963
DOI: 10.3390/ijms25115775 -
International Journal of Molecular... May 2024Micro-sized particles of synthetic polymers (microplastics) are found in all parts of marine ecosystems. This fact requires intensive study of the degree of danger of...
Micro-sized particles of synthetic polymers (microplastics) are found in all parts of marine ecosystems. This fact requires intensive study of the degree of danger of such particles to the life activity of hydrobionts and needs additional research. It is evident that hydrobionts in the marine environment are exposed to microplastics modified by biotic and abiotic degradation. To assess the toxic potential of aging microplastic, comparative studies were conducted on the response of cytochemical and genotoxic markers in hemocytes of the mussel (Gould, 1850) after exposure to pristine and photodegraded (UV irradiation) polystyrene microparticles (µPS). The results of cytochemical tests showed that UV-irradiated µPS strongly reduced metabolism and destabilized lysosome membranes compared to pristine µPS. Using a Comet assay, it was shown that the nuclear DNA of mussel hemocytes showed high sensitivity to exposure to both types of plastics. However, the level of DNA damage was significantly higher in mussels exposed to aging µPS. It is suggested that the mechanism of increased toxicity of photo-oxidized µPS is based on free-radical reactions induced by the UV irradiation of polymers. The risks of toxic effects will be determined by the level of physicochemical degradation of the polymer, which can significantly affect the mechanisms of toxicity.
Topics: Animals; Mytilus; Microplastics; Polystyrenes; DNA Damage; Hemocytes; Water Pollutants, Chemical; Ultraviolet Rays; Comet Assay
PubMed: 38891928
DOI: 10.3390/ijms25115740 -
International Journal of Molecular... May 2024Photoprotective properties of 1,25-dihydroxyvitamin D (1,25(OH)D) to reduce UV-induced DNA damage have been established in several studies. UV-induced DNA damage in skin...
Photoprotective properties of 1,25-dihydroxyvitamin D (1,25(OH)D) to reduce UV-induced DNA damage have been established in several studies. UV-induced DNA damage in skin such as single or double strand breaks is known to initiate several cellular mechanisms including activation of poly(ADP-ribose) (pADPr) polymerase-1 (PARP-1). DNA damage from UV also increases extracellular signal-related kinase (ERK) phosphorylation, which further increases PARP activity. PARP-1 functions by using cellular nicotinamide adenine dinucleotide (NAD+) to synthesise pADPr moieties and attach these to target proteins involved in DNA repair. Excessive PARP-1 activation following cellular stress such as UV irradiation may result in excessive levels of cellular pADPr. This can also have deleterious effects on cellular energy levels due to depletion of NAD+ to suboptimal levels. Since our previous work indicated that 1,25(OH)D reduced UV-induced DNA damage in part through increased repair via increased energy availability, the current study investigated the effect of 1,25(OH)D on UV-induced PARP-1 activity using a novel whole-cell enzyme- linked immunosorbent assay (ELISA) which quantified levels of the enzymatic product of PARP-1, pADPr. This whole cell assay used around 5000 cells per replicate measurement, which represents a 200-400-fold decrease in cell requirement compared to current commercial assays that measure in vitro pADPr levels. Using our assay, we observed that UV exposure significantly increased pADPr levels in human keratinocytes, while 1,25(OH)D significantly reduced levels of UV-induced pADPr in primary human keratinocytes to a similar extent as a known PARP-1 inhibitor, 3-aminobenzamide (3AB). Further, both 1,25(OH)D and 3AB as well as a peptide inhibitor of ERK-phosphorylation significantly reduced DNA damage in UV-exposed keratinocytes. The current findings support the proposal that reduction in pADPr levels may be critical for the function of 1,25(OH)D in skin to reduce UV-induced DNA damage.
Topics: Humans; Ultraviolet Rays; Poly (ADP-Ribose) Polymerase-1; Vitamin D; DNA Damage; Keratinocytes; Calcitriol; DNA Repair; Phosphorylation
PubMed: 38891771
DOI: 10.3390/ijms25115583