Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This ...study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C‐X‐C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats.
Highlights
Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats.
In the uterus, expression of matrix metallopeptidase 9 (MMP9), C‐X‐C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure,
In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure.
Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.
Ultraviolet (UV) sterilization of kitchenware is considered environmentally friendly and economical. However, there are many cases of extended UV irradiation, which raises concerns about the release ...of hazardous substances. Here, we investigated the migration of monomers, plastic additives, and non-intentionally added substances (NIAS) from food utensils made of melamine–formaldehyde resin into food simulants after UV irradiation for up to 7 d. The migration of monomers (melamine and formaldehyde) was analyzed using a high-performance liquid chromatograph with a diode array detector. When irradiated with a UV lamp for 7 d, the release of melamine from food utensils made of melamine–formaldehyde resins increased by up to 85-fold compared with that from the unexposed samples. Formaldehyde release increased up to 4-fold after UV exposure. UV exposure led to a sustained increase in melamine migration in a time-dependent manner. Formaldehyde release also increased on the first day, but plateaued after seven days of exposure. Safety assessment demonstrated that there is a low risk of melamine and formaldehyde exposure of up to 11.78% and 7.95%, respectively, compared with the tolerable daily intake. Non-target screening analysis of plastic additives and NIAS from melamine–formaldehyde resin and other synthetic resins was performed using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Exposure of melamine–formaldehyde resin to UV for 7 d drastically increased the release of plastic additives and NIAS. In contrast, for other synthetic resins (polypropylene, polyamide, polyethylene, polyethylene terephthalate, and silicone), the peaks of these compounds disappeared or decreased after UV exposure, indicating that the melamine–formaldehyde resin is less resistant to UV degradation than other synthetic resins.
•Effects of long-term UV exposure on melamine–formaldehyde utensils were studied.•Melamine and formaldehyde migration under UV exposure was time-dependent.•The risk from melamine and formaldehyde after UV exposure was acceptably low.•UV increased the release of plastic additives and NIAS from melamine resin.•Other synthetic resins showed a decrease tendency the release of plastic additives and NIAS.
Cigarette smoke (CS) causes about 480,000 deaths each year worldwide and is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular ...problems. In the present study, the effects of acrylonitrile (AN), benzo(a)pyrene (B(a)P), formaldehyde (FOR), isoprene (ISO), nicotine-derived nitrosamine ketone (NNK), which are the main components of CS, on the proliferation, invasion, and the epithelial-mesenchymal transition (EMT) process of human Ishikawa endometrial adenocarcinoma cells were investigated. Treating Ishikawa cells with CS components resulted in increased cell growth and altered expression of cell cycle-related genes: the protein expression of cyclin D & E increased, while the levels of p21 & p27 were reduced following treatment of these five CS components. In addition, CS components increased the invasion capacity of Ishikawa cells. The expression of the epithelial markers, E-cadherin and occludin, were significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by CS components. In dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay, ROS production increased by treatment of CS components. The CS components activated the ROS-p38 MAPK-EMT pathway by increasing the level of phosphorylated p38 MAPK and p44/42 (ERK1/2), and by up-regulating Snail and Slug, the transcription factors for EMT. Taken together, these results indicate that CS components can promote progression of endometrial adenocarcinoma via increasing cell proliferation and the ROS-mediated EMT process.
•CS exposure induced the endometrial cancer cell proliferation by altering cell cycle-related genes.•CS exposure promoted the invasion capacity of Ishikawa cells by altering EMT markers.•CS exposure increased ROS production and activated p38 MAPK-EMT pathway.
The contribution of miRNA to the pathogenesis of acute kidney injury (AKI) is not well understood. Here we evaluated an integrative network of miRNAs and mRNA data to discover a possible master ...regulator of AKI. Microarray analyses of the kidneys of mice treated with cisplatin were used to extract putative miRNAs that cause renal injury. Of them, miR-122 was mostly downregulated by cisplatin, whereas miR-34a was upregulated. A network integrating dysregulated miRNAs and altered mRNA expression along with target prediction enabled us to identify Foxo3 as a core protein to activate p53. The miR-122 inhibited Foxo3 translation as assessed using an miR mimic, an inhibitor, and a Foxo3 3′-UTR reporter. In a mouse model, Foxo3 levels paralleled the degree of tubular injury. The role of decreased miR-122 in inducing Foxo3 during AKI was strengthened by the ability of the miR-122 mimic or inhibitor to replicate results. Increase in miR-34a also promoted the acetylation of Foxo3 by repressing Sirt1. Consistently, cisplatin facilitated the binding of Foxo3 and p53 for activation, which depended not only on decreased miR-122 but also on increased miR-34a. Other nephrotoxicants had similar effects. Among targets of p53, Phlda3 was robustly induced by cisplatin, causing tubular injury. Consistently, treatment with miR mimics and/or inhibitors, or with Foxo3 and Phlda3 siRNAs, modulated apoptosis. Thus, our results uncovered an miR integrative network regulating toxicant-induced AKI and identified Foxo3 as a bridge molecule to the p53 pathway.
Ionic liquids have gained increasing attention in the chemical industry as potential green substitutes for traditional solvents. However, little is known about toxicity of ionic liquids on the skin, ...a major exposure portal to toxic substances. Here, we evaluated dermal toxicity of ionic liquids using human keratinocyte and fibroblast cell line, 3D reconstructed human epidermis, and full-thickness model to investigate underlying mechanisms. Cytotoxicity of ionic liquids was evaluated for representative anions, TFSI, PF6, BF4, and DCA, as well as for cations, EMIM, BMPY, TBA and Zn, in human keratinocyte cell line, HaCaT, and human dermal fibroblasts. In our results, significant cytotoxicity was induced by ionic liquids with TFSI in both cell lines. Notably, cytotoxicity of TFSI containing ionic liquids was comparable to xylene, a toxic conventional organic solvent. Fluorescent and flow cytometric analysis revealed that TFSI-exposed cells underwent necrotic cell death. Reactive oxygen species (ROS) was increased while the amount of glutathione was decreased by TFSI in dose-dependent manner, which was reversed by antioxidant, N-acetylcysteine. In 3D reconstructed human epidermis and full-thickness model, a single application of TFSI induced toxicity although it was minimal and largely limited to epidermal layer. Collectively, these results demonstrated potential dermal toxicity of ionic liquids.
•Here, we demonstrate the dermal toxicity of ionic liquids against skin cells and 3D skin model.•Of tested ionic liquids, those containing TFSI anion exhibited strongest toxicity.•TFSI induced ROS generation and GSH depletion which led to necrotic cell deaths.
•Alcoholic liver injury in rats fed a liquid ethanol diet for 6 wk is alleviated by betaine supplementation.•Ethanol intake reduces hepatic SAM, cysteine, GSH levels, and cytosolic antioxidant ...capacity against ROS.•Betaine treatment prevents the changes in S-amino acid metabolism and elevates cysteine availability for GSH synthesis.•Liver protection by betaine is attributed to enhancement of antioxidant defense via regulation of S-amino acid metabolism.•Betaine supplementation for the final 2 wk also reverses alcoholic liver, suggesting its therapeutic value.
Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.
•BPA up-regulated mRNA and protein levels of ERα and IGF-1R.•Resveratrol down-regulated ERα, IGF-1R, p-IRS-1, and p-Akt1/2/3, and cyclin D1.•Resveratrol is a novel candidate for prevention of tumor ...progression caused by BPA.
Endocrine disrupting chemicals (EDCs) and estrogens appear to promote development of estrogen-dependent cancers, including breast and ovarian carcinomas. In this study, we evaluated the cell viability effect of BPA on BG-1 human ovarian cancer cells, along with the growth inhibitory effect of resveratrol (trans-3,4,5-trihydroxystilbene; RES), a naturally occurring phytoestrogen. In addition, we investigated the underlying mechanism(s) of BPA and RES in regulating the interaction between estrogen receptor alpha (ERα) and insulin-like growth factor-1 receptor (IGF-1R) signals, a non- genomic pathway induced by 17β-estradiol (E2). BPA induced a significant increase in BG-1 cell growth and up-regulated mRNA levels of ERα and IGF-1R. In parallel with its mRNA level, the protein expression of ERα was induced, and phosphorylated insulin receptor substrate-1 (p-IRS-1), phosphorylated Akt1/2/3, and cyclin D1 were increased by BPA or E2. However, RES effectively reversed the BG-1 cell proliferation induced by E2 or BPA by inversely down-regulating the expressions of ERα, IGF-1R, p-IRS-1, and p-Akt1/2/3, and cyclin D1 at both transcriptional and translational levels. Taken together, these results suggest that RES is a novel candidate for prevention of tumor progression caused by EDCs, including BPA via effective inhibition of the cross-talk of ERα and IGF-1R signaling pathways.
Scope
Taurine, which is abundant in seafood, has antiatherogenic activities in both animals and humans; however, its molecular target has been elusive. We examined whether taurine could activate ...liver X receptor‐α (LXR‐α), a critical transcription factor in the regulation of reverse cholesterol transport in macrophages.
Methods and results
Taurine bound directly to LXR‐α in a reporter gene assay, time‐resolved fluorescence resonance energy transfer analysis, and limited protease digestion experiment. Macrophage cells incubated with taurine showed reduced cellular cholesterol and induced medium cholesterol in a dose‐dependent manner with the induction of ATP‐binding cassette transporter A1 and G gene and protein expression. In hepatocytes, taurine significantly induced Insig‐2a levels and delayed nuclear translocation of the sterol regulatory element‐binding protein 1 (SREBP‐1) protein, resulting in a dose‐dependent reduction in the cellular lipid levels without inducing the expression of fatty acid synthesis genes.
Conclusion
Taurine is a direct LXR‐α ligand, represses cholesterol accumulation, and modulates the expression of genes involved in reverse cholesterol transport in macrophages, without inducing hepatic lipogenesis. The induction of Insig‐2a suppressed the nuclear translocation of SREBP‐1c.
In this study, we confirmed that ursolic acid, a plant triterpenoid, activates peroxisome proliferator-activated receptor (PPAR)-α in vitro. Surface plasmon resonance and time-resolved fluorescence ...resonance energy transfer analyses do not show direct binding of ursolic acid to the ligand-binding domain of PPAR-α; however, ursolic acid enhances the binding of PPAR-α to the peroxisome proliferator response element in PPAR-α-responsive genes, alters the expression of key genes in lipid metabolism, significantly reducing intracellular triglyceride and cholesterol concentrations in hepatocytes. Thus, ursolic acid is a PPAR-α agonist that regulates the expression of lipid metabolism genes, but it is not a direct ligand of PPAR-α.
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