Nickel oxide nanoparticles (NiO‐NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO‐NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO‐NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO‐NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non‐cancerous mouse skin mitochondria. Our results revealed that NiO‐NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO‐NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti‐MCM drug. 相似文献
Cysteine is a nonessential amino acid in poultry nutrition. Poultry diets are deficient in cysteine, but the bird’s cysteine need is met through the transsulfuration pathway (TSP) where homocysteine is converted to cysteine: a process catalyzed by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). Cysteine is also a major component of keratinized protein found in feathers, but the extent to which cysteine is involved in feather and skin development in poultry is unknown. We randomly assigned chicks to control and treatment (control diet plus 100?mg/kg body weight of propargylglycine which is an inhibitor of CTH) diets. The thickness of skin layers, primary feather follicle parameters, growth, and mRNA expression of CBS and CTH were measured. Inhibition of TSP corresponded with the upregulation of liver mRNA of both CBS and CTH and reduction in growth from 35 to 40 days of age. The epidermis thickness, feather follicle length, and diameter were reduced from 10 to 40 days of age. Incorporation of cysteine into keratinized protein may be more sensitive to the level of available cysteine than into nonkeratinized proteins. Thus, disruption of the TSP could affect the thermoregulatory ability of the bird. 相似文献
Dermal exposure to cumene hydroperoxide (CumOOH) during manufacturing processes is a toxicological issue for the industry. Its genotoxicity, mutagenic action, ability to promote skin tumour, capacity to induce epidermal hyperplasia, and aptitude to induce allergic and irritant skin contact dermatitis are well known. These toxic effects appear to be mediated through the activation to free radical species such as hydroxyl, alkoxyl, and alkyl radicals characterised basically by electron paramagnetic resonance (EPR) and spin-trapping (ST) techniques. To be a skin sensitiser CumOOH needs to covalently bind to skin proteins in the epidermis to form the antigenic entity triggering the immunotoxic reaction. Cleavage of the O–O bond allows formation of unstable CumO?/CumOO? radicals rearranging to longer half-life specific carbon-centred radicals R? proposed to be at the origin of the antigen formation. Nevertheless, it is not still clear which R? is precisely formed in the epidermis and thus involved in the sensitisation process. The aim of this work was to elucidate in conditions closer to real-life sensitisation which specific R? are formed in a 3D reconstructed human epidermis (RHE) model by using 13C-substituted CumOOH at carbon positions precursors of potentially reactive radicals and EPR-ST. We demonstrated that most probably methyl radicals derived from β-scission of CumO? radicals occur in RHE through a one-electron reductive pathway suggesting that these could be involved in the antigen formation inducing skin sensitisation. We also describe a coupling between nitroxide radicals and β position 13C atoms that could be of an added value to the very few examples existing for the coupling of radicals with 13C atoms. 相似文献
Objective: The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS).
Methods: Limited (lSSc, n?=?76) and diffuse SSc (dSSc, n?=?41) fulfilling the ACR/EULAR 1980 and 2013 classification criteria for SSc and asymptomatic controls (n?=?9) were included. PRO-C1, PRO-C3 and PRO-C6 were measured in serum.
Results: LSSc compared to dSSc were significantly older, had longer disease duration and lower mRSS. PRO-C3 was higher in early dSSc compared to early lSSc (mean [95 percentile], 27.4 [13.1–39.1] ng/mL vs 14.9 [8.2–28.8] ng/mL, p?=?0.006). PRO-C6 levels were higher in early dSSc compared to early lSSc and late dSSc (early dSSc: 28.2 [10.4–92.3] ng/ml vs early lSSc: 11.0 [6.9–28.5] ng/ml; p?=?0.006 and late dSSc: 12.6 [6.5–25.3] ng/mL, p?=?0.04). No difference was observed with PRO-C1. PRO-C3 and PRO-C6 were moderately correlated with mRSS with R-partials of 0.36 (p?<?0.001) and 0.29 (p?=?0.002), respectively
Conclusion: Measures of type III and VI collagen formation are potential objective biomarkers of fibrosis in systemic sclerosis. These biomarkers could be useful in monitoring the disease and efficacy of treatment. 相似文献
Shikonin, a naphthoquinone pigment isolated from the Chinese herbal Zicao, has been shown to exhibit antioxidant and anticancer effects. In the present study, we investigated the antiproliferative and pro-apoptotic effects of shikonin on A431 cells and explored the underlying molecular mechanisms. In the present study, our results showed that shikonin significantly inhibited the growth of A431 cells in a concentration- and time-dependent manner, and caused cell cycle arrest by upregulation of p21 and p27, and downregulation of cyclins and cyclin-dependent kinases. In addition, shikonin evidently induced apoptosis due to decreasing Bcl-2 expression, increasing Bax expression, activating caspase and inactivating NF-κB, while pretreatment with a pan-caspase inhibitor Z-Asp-CH2-DCB abrogated shikonin-induced apoptosis. Moreover, EGF could significantly increase the NF-κB DNA-binding activity and reversed the shikonin-induced inactivation of NF-κB. As anticipated AG1478 (EGFR inhibitor) and Bay11-7082 (NF-κB inhibitor) blocked EGF-reversed the inactivation of NF-κB induced by shikonin. Our data also showed that EGF could evidently reverse the shikonin-induced decreases in cell viability and increases in apoptosis. Then, the NF-κB inhibitors such as Bay11-7082, SN50, Helenalin and the EGFR inhibitor AG1478 and its downstream inhibitor such as PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and STAT3 inhibitor Stattic dramatically blocked EGF-reversed decreases in cell viability and increases in apoptosis induced by shikonin. Collectively, our findings indicated that shikonin inhibited cell growth and caused cell cycle arrest of the A431 cells through the regulation of apoptosis. Moreover, these effects were mediated at least partially by suppressing the activation of the EGFR–NF-κB signaling pathways. 相似文献
In this study, the development of integument and cutaneous glands in the toad Rhinella granulosa (Bufonidae) at different larval stages and in postmetamorphic and adult forms was examined. The analyses were conducted using histological, ultrastructural and morphometric methods. The results showed that cellular aggregations of precursor epidermal glands start to appear in stage 31 of (Herpetologica, 16, 1960 and 183) and then proliferate and invade the dermis. After stage 41, granular and mucous glands are very similar to those found in adults. The granular glands are syncytial and are surrounded by a distinct layer of myoepithelial cells. In the region of parotoid macroglands, the granular glands accumulate and their alveoli progressively increase until they reach adult size. An analysis by scanning electron microscopy showed the inner distribution of the syncytial nuclei and the myoepithelial cells. The morphological changes observed in the integument of tadpoles are associated with the gradual adaptation to terrestrial environments by preparing the individual for future chemical defence against predators and micro‐organisms. 相似文献