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Burden of disease induced by public overexposure to solar ultraviolet radiation (SUVR) at the national and subnational levels in Iran, 2005–2019
2022
Abtahi, Mehrnoosh | Dobaradaran, Sina | Koolivand, Ali | Jorfi, Sahand | Saeedi, Reza
Estimating the burden of diseases induced by overexposure to solar ultraviolet radiation (SUVR) can help to prioritize environmental health interventions. The age-sex specific and cause-specific mortality and disability-adjusted life years (DALYs) attributable to overexposure to SUVR at the national and subnational levels in Iran, 2005–2019 were estimated. The burden of disease induced by overexposure to SUVR was quantified in four steps as follows: (1) estimating exposure to SUVR, (2) estimating total incidences and deaths of target causes, (3) assessing population attributable fractions of the target causes for the SUVR, and (4) calculating the attributable burden of disease. The attributable DALYs, deaths, age-standardized DALY rate, and age-standardized death rate at the national level were determined to be respectively 21896, 252, 42.59, and 0.56 in 2005 and were respectively changed to 28665, 377, 38.76, and 0.53 in 2019. The contributions of causes in the attributable DALYs at the national level were different by year and sex and for both sexes in 2019 were as follows: 46.15% for cataract, 20.36% for malignant skin melanoma, 16.07% for sunburn, 12.41% for squamous-cell carcinoma, and 5.01% for the other five causes. The contributions of population growth, population ageing, risk exposure, and risk-deleted DALY rate in the temporal variations of the attributable burden of disease in the country were +20.73%, +20.68%, +2.01%, and −12.51%. The highest and lowest provincial attributable age-standardized DALY rates in 2019 were observed in Fars (46.8) and Ardebil (32.7), respectively. The burden of disease induced by exposure to SUVR caused relatively low geographical inequality in health status in Iran. Due to increasing trends of the SUVR as well as the attributable burden of disease, the preventive interventions against the SUVR overexposure should be considered in the public health action plan all across the country.
Показать больше [+] Меньше [-]Di-(2-ethylhexyl) phthalate enhances melanoma tumor growth via differential effect on M1-and M2-polarized macrophages in mouse model
2018
Yi, Chae-uk | Park, Sojin | Han, Hae-Kyoung | Gye, Myung Chan | Moon, Eun-Yi
Phthalates are widely used as plasticizers that influence sexual and reproductive development. Here, we investigated whether di-(2-ethylhexyl) phthalate (DEHP) affects macrophage polarization that are associated with tumor initiation and progression. No changes were observed in LPS- or ConA-stimulated in vitro spleen B or T cell proliferation for 48 h, respectively. In contrast, macrophage functions were inhibited in response to DEHP for 12 h as judged by LPS-induced H₂O₂ and NO production and zymosan A-mediated phagocytosis. When six weeks old male mice were pre-exposed to 4.0 mg/kg DEHP for 21 days before the injection of B16F10 melanoma cells and post-exposed to 4.0 mg/kg DEHP for 7 days, tumor nodule formation and the changes in tumor volume were higher than those in control group. Furthermore, when male mice were intraperitoneally pretreated with DEHP for 3 or 4 weeks and peritoneal exudate cells (PECs) or bone marrow-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), the expression of COX-2, TNF-α, and IL-6 was reduced in DEHP-pretreated cells as compared with that in LPS-stimulated control cells. While the production of nitric oxide (NO) for 18 h was reduced by LPS-stimulated PECs and M1-type BMDMs, IL-4 expression was enhanced in LPS-stimulated BMDMs. When BMDMs were incubated with IL-4 for 30 h, arginase 1 for M2-type macrophages was increased in transcriptional and translational level. Data implicate that macrophages were differentially polarized by DEHP treatment, which reduced M1-polarzation but enhanced M2-polarization. Taken together, these data demonstrate that DEHP could affect in vivo immune responses of macrophages, leading to the suppression of their tumor-preventing ability. This suggests that individuals at high risk for tumor incidence should avoid long-term exposure to various kind of phthalate including DEHP.
Показать больше [+] Меньше [-]BDE-209 and TCDD enhance metastatic characteristics of melanoma cells after chronic exposure
2022
Silva Filho, Benisio Ferreira | Filipak Neto, Francisco | Marchi, Micheli de | Moggio, Erick Laurent | Rossi, Izadora Volpato | Sabatke, Bruna | Ramirez, Marcel Ivan | Lucena, Miguel Clodomiro dos Santos | Todeschini, Adriane Regina | Oliveira Ribeiro, Ciro Alberto de
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and BDE-209 (decabromodiphenyl ether) are persistent organic pollutants (POPs) produced by industrial activities and associated with several diseases. TCDD is a known human carcinogen, but few studies investigated about the effects of exposure to both compounds, i.e., whether BDE-209 and TCDD can render tumor cells more aggressive and metastatic. In the current study we investigated if the exposure of B16–F1 and B16–F10 melanoma murine cells to environmental relevant concentrations of TCDD and BDE-209 at 24 h and 15-day exposure modulates the expression of genes related to metastasis, making the cells more aggressive. Both pollutants did not affect cell viability but lead to increase of cell proliferation, including the upregulation of vimentin, MMP2, MMP9, MMP14 and PGK1 gene expression and downregulation of E-cadherin, TIMP2, TIMP3 and RECK, strongly suggesting changes in cell phenotypes defined as epithelial to mesenchymal transition (EMT) in BDE-209 and TCDD-exposed cells. Foremost, increased expression of metalloproteinases and decreased expression of their inhibitors made B16–F1 cells similar the more aggressive B16–F10 cell line. Also, the higher secretion of extracellular vesicles by cells after acute exposure to BDE-209 could be related with the phenotype changes. These results are a strong indication of the potential of BDE-209 and TCDD to modulate cell phenotype, leading to a more aggressive profile.
Показать больше [+] Меньше [-]The pigmentation interference of bisphenol F and bisphenol A
2020
Mu, Xiyan | Liu, Jia | Yuan, Lilai | Huang, Ying | Qian, Le | Wang, Chengju
Bisphenol A (BPA) and bisphenol F (BPF) are widely distributed in the environment and daily consumptions, leading to exposure toward human and environmental animals. The potential risk of bisphenol analogs on pigment and skin health is not well documented. In this study, we found that 0.05 mg/L BPF (tolerated daily intake (TDI) value of BPA) affected the particle size and color density of zebrafish melanin. While BPA caused less depigmentation effect toward zebrafish with effective concentration of 5.0 mg/L. The downregulation of melanin synthases induced by BPF is associated with the reduction in melanin. Molecular dynamics indicated that both BPF and BPA could act as ligands of zebrafish and human Tyr family proteins; however, these compounds have completely different energetics and spatial steric effects, potentially explaining their varying depigmentation effects. Additionally, an in vitro assay using A375 melanoma cells demonstrated that the inhibitory effect of BPF on human melanin production was primarily attributed to Tyr inhibition. These findings provide an important basis for understanding the molecular mechanisms of BPF and BPA in melanin inhibition, and the results reflect the skin pigmentation interference risk of these compounds, which are ubiquitous in everyday personal products.
Показать больше [+] Меньше [-]Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study
2018
Moslehi, Roxana | Zeinomar, Nur | Boscoe, Francis P.
Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996–2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR.Population-based rates representing all incident cases of melanoma (1996–2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated.We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996–2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state.The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56–0.64) and 0.46 (95%CI: 0.42–0.49), respectively, for Iran and 22.78 (95%CI: 22.42–23.14) and 16.61 (95%CI: 16.30–16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78–40.29) for males and 36.11 (95%CI: 33.69–38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state.The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the influence of other extrinsic and intrinsic factors on the risk of this malignancy.
Показать больше [+] Меньше [-]The assessment of the protective impact of spidroin extract against UV-A radiation damage by using earthworms (Aporrectodea caliginosa) as a robust human skin model via macroscopic and histological observations
2022
El-Aziz, Fatma El-Zahraa A Abd | Ismail, May S. | Askary, Ahmad El | El-kott, Attalla F. | Tantawy, Ahmed A.
Numerous studies have confirmed the damage caused by excessive exposure to ultraviolet-A rays. Malignant melanoma and skin cancer are two of the most serious health consequences. Thus, the UV-A protectant is intended to protect the skin, especially the two primary layers of skin (epidermis that represents the interface between the body and its surroundings and dermis). Spider silk is the most powerful natural fibre due to its regeneration, biocompatibility, antimicrobial, wound healing, antiseptic, and blood clotting properties. This work targeted to determine the protective effect of spidroin extract against UV-A radiation damage. Earthworms Aporrectodea caliginosa were collected from Assiut University’s farm. Each set of ten earthworms was separated into six groups and placed in a plastic container. Webs of spiders collected from trees and old houses. Spidroin was extracted and utilised in this work to determine the potential effects of topical application on UV-A protection. The experiment is divided into two sections: (1) UV-A exposure and (2) the use of spidroin extract to protect the earthworms from ultraviolet radiation. Two control groups (1،2) of worms were not received UV-A exposure, and four groups (3,4,5,6) were exposed to UVR-A. In contrast, groups (5,6) were received spidroin extract before exposure to UV-A. Each group from the groups (3,4,5,6) was exposed for three consecutive days (¼ hour/day, ½ hour/day, and 1 h/day), using a UV-Lamp with a wavelength of 366 nm. The histopathological changes revealed that after 1⁄4 h of UV exposure, the cuticle was swollen with a slightly detached epithelium. The cuticle was down after 1⁄2 h of exposure, and the epidermis was totally damaged and necrosed. After 1 h, the exposure showed destruction of the epidermis in the circular muscle with a loss of muscle filament integrity, varying size, and altered nucleus form, along with mild disintegration of longitudinal muscle. Spidroin extract is critical for earthworm protection against UV-A radiation damage and able to regeneration. For the first time, morphological and histological analysis was established to detect the Spidroin extract evaluated for topical application on earthworms. Earthworms can be considered as a robust human skin model prior to UV-A exposure. It induces a complete protective effect against UV-A radiation damage in earthworms.
Показать больше [+] Меньше [-]Polybrominated diphenyl ethers BDE-47 and BDE-99 modulate murine melanoma cell phenotype in vitro
2022
Steil, Gisleine Jarenko | Buzzo, João Luiz Aldinucci | de Oliveira Ribeiro, Ciro Alberto | Filipak Neto, Francisco
Cancer is one of the leading causes of mortality worldwide. Even with the advances of pharmaceutical industry and treatments, the mortality rate for various types of cancer remains high. In particular, phenotypic alterations of tumor cells concerning drug efflux, migratory and invasive capabilities may represent a hurdle for cancer treatment and contribute to poor prognosis. In the present study, we investigated the effects of polybrominated diphenyl ethers (PBDEs) used as flame retardants on phenotypic features of melanoma cells that are important for cancer. Murine melanoma B16-F1 (less metastatic) and B16-F10 (more metastatic) cells were exposed to 0.01–1.0 nM of BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether), BDE-99 (2,2′,4,4′,5-pentabromodiphenyl ether), and the mixture of both (at 0.01 nM) for 24 h (acute exposure) and 15 days (chronic exposure). The polybrominated diphenyl ethers (PBDEs) did not affect cell viability but led to increased drug efflux transporter activity, cell migration, and colony formation, as well as overexpression of Abcc2 (ATP-binding cassette subfamily C member 2), Mmp-2 (matrix metalloproteinase-2), Mmp-9 (matrix metalloproteinase-9), and Tp53 (tumor protein p53) genes and downregulation of Timp-3 (tissue inhibitor of metalloproteinase 3) gene in B16-F10 cells. These effects are consistent with increased aggressiveness and malignancy of tumors due to exposure to the flame retardants and raise some concerns on the effects such chemicals may have on melanoma treatment and cancer prognosis.
Показать больше [+] Меньше [-]Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera
2020
Sivasankarapillai, Vishnu Sankar | Madhu Kumar Nair, Reshmi | Rahdar, Abbas | Bungau, Simona | Zaha, Dana Carmen | Aleya, Lotfi | Tit, Delia Mirela
Cancer is still considered a “hopeless case”, besides all of the advancements in oncology research. On the other hand, the natural products, as effective lead molecules, have gained significant interest for research due to the absence of toxic and harmful side effects usually associated with conventional treatment methods. Medicinal properties of herbal plants are strongly evidenced in traditional medicine from ancient times. In the context above, withaferin A (WA) was identified as the active principle of the plant Withania somnifera, its molecule being reported to have excellent anticancer and tumour inhibition activities in various cell lines. Furthermore, the in silico approaches in the medicinal chemistry of WA revealed the biological targets and gave momentum for the research that leads to many amazing pharmacological activities of WA which are not yet explored. This includes a broad spectrum of anticancer actions manifested in different organs (breast, pancreas, colon), melanoma and B cell lymphoma, etc. This review is an extensive survey of the most recent anticancer studies reported for WA, along with its mechanism of action and details about its in vitro and/or in vivo behaviour.
Показать больше [+] Меньше [-]Influence of magnetite incorporation into chitosan on the adsorption of the methotrexate and in vitro cytotoxicity
2022
Bruckmann, Franciele da Silva | Rossato Viana, Altevir | Tonel, Mariana Zancan | Fagan, Solange Binotto | Garcia, Wagner Jesus da Silva | Oliveira, Artur Harres de | Dorneles, Lucio Strazzabosco | Roberto Mortari, Sergio | Silva, William Leonardo da | Silva, Ivana Zanella da | Rhoden, Cristiano Rodrigo Bohn
Emerging pollutants are a group of substances involved in environmental contamination resulting mostly from incomplete drug metabolism, associated with inadequate disposal and ineffective effluent treatment techniques. Methotrexate (MTX), for instance, is excreted at high concentrations in unchanged form through the urine. Although the MTX is still effective in cancer and autoimmune disease treatment, this drug shows the ability of bioaccumulation and toxicity to the organism. Thus, the present work aimed to evaluate the adsorption of the MTX drug onto magnetic nanocomposites containing different amounts of incorporated magnetite (1:1, 1:5, and 1:10 wt%), combining the theoretical–experimental study as well as the in vitro cytotoxicity. Moreover, equilibrium studies (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Hill, Redlich-Peterson, and Sips), kinetic (PFO, PSO, and IPD), and thermodynamic (ΔG°, ΔH°, and ΔS°) were used to describe the experimental data, and ab initio simulations were employed in the theoretical study. Magnetic nanocomposites were synthesized by the co-precipitation method using only FeCl₂ as the iron precursor. Adsorbents were characterized by FTIR, XRD, Raman, SEM–EDS, BET, and VSM analysis. Meanwhile, cytotoxic effects on L929 and A375 cell lines were evaluated through MTT, NR, and LDH assays. The adsorption of the MTX was carried out in a typical batch system, exploring the different experimental conditions. The theoretical study suggests the occurrence of chemisorption between CS·Fe₃O₄-MTX. The maximum adsorption capacity of MTX was 285.92 mg g⁻¹, using 0.125 g L⁻¹ of CS·Fe₃O₄ 1:1, with an initial concentration of the MTX (50 mg L⁻¹), pH 4.0 at 293 ± 1.00 K. The best adjustment of equilibrium and kinetic data were the Sips (low values for statistical errors) and PSO (qₑ = 96.73 mg g⁻¹) models, respectively. Thermodynamic study shows that the adsorption occurred spontaneously (ΔG° < 0), with exothermic (ΔH° = − 4698.89 kJ mol⁻¹) and random at the solid-solution interface (ΔS° = 1,476,022.00 kJ mol⁻¹ k⁻¹) behavior. Finally, the in vitro study shows that magnetic nanomaterials exhibit higher cytotoxicity in melanoma cells. Therefore, the magnetic nanocomposite reveals to be not only an excellent tool for water remediation studies but also a promising platform for drug delivery.
Показать больше [+] Меньше [-]Cytotoxic activity of selenosulfate versus selenite in tumor cells depends on cell line and presence of amino acids
2016
Hinrichsen, Sinikka | Planer-Friedrich, Britta
Based on acute cytotoxicity studies, selenosulfate (SeSO₃ ⁻) has been suggested to possess a generally higher toxic activity in tumor cells than selenite. The reason for this difference in cytotoxic activity remained unclear. In the present study, cytotoxicity tests with human hepatoma (HepG2), malignant melanoma (A375), and urinary bladder carcinoma cells (T24) showed that the selenosulfate toxicity was very similar between all three tested cell lines (IC₅₀ 6.6–7.1 μM after 24 h). It was largely independent of exposure time and presence or absence of amino acids. What changed, however, was the toxicity of selenite, which was lower than that of selenosulfate only for HepG2 cells (IC₅₀ > 15 μM), but similar to and higher than that of selenosulfate for A375 (IC₅₀ 4.7 μM) and T24 cells (IC₅₀ 3.5 μM), respectively. Addition of amino acids to T24 cell growth medium downregulated short-term selenite uptake (1.5 versus 12.9 ng Se/10⁶ cells) and decreased its cytotoxicity (IC₅₀ 8.4 μM), rendering it less toxic than selenosulfate. The suggested mechanism is a stronger expression of the xc ⁻ transport system in the more sensitive T24 compared to HepG2 cells which creates a reductive extracellular microenvironment and facilitates selenite uptake by reduction. Selenosulfate is already reduced and so less affected. The cytotoxic activity of selenosulfate and selenite to tumor cells therefore depends on the sensitivity of each cell line, supplements like amino acids as well as the reductive state of the extracellular environment.
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