Human & Experimental Toxicology最新文献

Background: N-propylparaben (PP), a type of paraben, is commonly used as a preservative or antibacterial agent in daily chemicals, medicine, food, cosmetics, feed, and various industrial preservatives. Although PP promotes the growth of human breast adenocarcinoma (MCF-7) cells by activating the human estrogen receptor (ER), the mechanism responsible for this type of programmed cell proliferation is poorly understood.

Objective: To clarify the effect of PP on cell metabolic function and the potential molecular mechanism of PP induced MCF-7 cell proliferation from a new perspective.

Methods: To use high-resolution mass spectrometry-based metabolomics combined with bioinformatics analysis to analyze the molecular mechanism.

Results: The results illustrated that differential endogenous compounds related to the effects of PP on cell metabolic functions were detected. PP was found to promote glycolysis in MCF-7 cells and enhance the tricarboxylic acid cycle (TCA cycle) in mitochondria, thus improving the energy supply to these tumor cells for metabolic function and promotion of rapid proliferation. Moreover, we found that PP promoted cell proliferation by affecting the mitogen-activated protein kinase (MAPK) signaling pathway of MCF-7 cells.

Conclusion: Our results revealed the molecular mechanism of low concentration PP promoting MCF-7 cell proliferation by activating ER.

Background: Circular RNA (circRNA) has been reported to regulate respiratory diseases. In the study, we aimed to elucidate the role of circ_0000157 in smoke-related chronic obstructive pulmonary disease (COPD) and the inner mechanism.

Methods: COPD-like cell injury was induced by treating human bronchial epithelioid cells (16HBE) with cigarette smoke extract (CSE). The expression of circ_0000157, miR-149-5p, bromodomain containing 4 (BRD4), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blotting. Enzyme-linked immunosorbent assay was performed to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Malondialdehyde (MDA) production was detected by a lipid peroxidation MDA assay kit. Superoxide dismutase (SOD) activity was analyzed by a SOD activity assay kit.

Results: Circ_0000157 and BRD4 expression were upregulated, while miR-149-5p expression was downregulated in the blood of smokers with COPD and CSE-induced 16HBE cells compared with control groups. CSE treatment inhibited 16HBE cell proliferation and induced cell apoptosis, inflammation, and oxidative stress; however, these effects were remitted when circ_0000157 expression was decreased. In addition, circ_0000157 acted as a miR-149-5p sponge and regulated CSE-caused 16HBE cell damage by targeting miR-149-5p. The overexpression of BRD4, a target gene of miR-149-5p, attenuated the inhibitory effects of miR-149-5p introduction on CSE-induced cell damage. Further, circ_0000157 modulated BRD4 expression by associating with miR-149-5p in CSE-treated 16HBE cells.

Conclusion: Circ_0000157 knockdown ameliorated CSE-caused 16HBE cell damage by targeting the miR-149-5p/BRD4 pathway, providing a potential therapeutic strategy for clinic intervention in COPD.

Riboflavin deficiency produces severe peripheral neve demyelination in young, rapidly growing chickens. While this naturally-occurring vitamin B2 deficiency can cause a debilitating peripheral neuropathy, and mortality, in poultry flocks, it can also be a useful experimental animal model to study the pathogenesis of reliably reproducible peripheral nerve demyelination. Moreover, restitution of normal riboflavin levels in deficient birds results in brisk remyelination. It is the only acquired, primary, demyelinating tomaculous neuropathy described to date in animals. The only other substance that causes peripheral nerve demyelination similar to avian riboflavin deficiency is tellurium and the pathologic features of the peripheral neuropathy produced by this developmental neurotoxin in weanling rats are also described.

The use of pesticides in farmland has increased considerably to protect crops against pests, weeds, and diseases. However, pesticides and/or their residues in ecosystems may affect non-target organisms. Indaziflam is a widely used herbicide in agricultural areas in the southern region of Turkey. Therefore, this study aimed to investigate the possible genotoxic and cytotoxic effects of indaziflam on HepG2 cells using comet assay, micronucleus assay, and xCELLigence. The HepG2 cells were treated with various concentrations of indaziflam for different duration of time based on xCELLigence results. Accordingly, the cells were incubated with indaziflam at final concentrations of 1, 5, 10, 20, 40, and 80 μg/mL for 96 h for cytotoxicity assay. To assess genotoxicity, cells were treated with indaziflam at final concentrations of 10, 40, and 100 μg/mL for 4 and 24 h. Ethanol was used as a solvent for indaziflam. Hydrogen peroxide (40 μM) was used as a positive control. Studies have revealed that indaziflam did not show a statistically cytotoxic effect at the tested doses. Nevertheless, genotoxicity studies showed that indaziflam induced both DNA strand breaks and micronucleus numbers depending on the exposure time and dose.

Spinal cord injury (SCI) is a destructive event in central nervous system (CNS) with the hallmark of deficits in neuronal function. Phoenixin-14 (PNX-14) is a reproductive peptide that also has neuroprotective effects. However, the role of PNX-14 in SCI has not yet been studied. In this study, we firstly investigated the effects of PNX-14 on the recovery of neurological dysfunction and microglial polarization in a SCI mice model. We demonstrated that PNX-14 improved the recovery of neurological dysfunction with increased Basso Mouse Scale (BMS) scores, reduced lesion area volume and Evans blue (EB) dye extravasation. PNX-14 alleviated neuronal apoptosis and neuroinflammation in mice underwent SCI. In vitro co-culture assay proved that PNX-14 protected neurons injury in response to LPS- activated BV-2 cells. PNX-14 suppressed the LPS- induced microglia M1 phenotype polarization with decreased expression of M1-associated markers (CD16 and iNOS) and increased expression of M2-associated markers (CD206 and Arg1). PNX-14 also suppressed LPS- caused decrease in anti-inflammatory cytokines TGF-β, IL-10, and IL-13, as well increase in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in BV2 cells. PNX-14 treatment caused increased PTEN expression and decreased p-Akt expression in BV2 cells against LPS induction. While inhibition of PTEN by SF1670 reversed the effects of PNX-14 on LPS- induced phenotypic transition of BV2 cells. Taken together, we found that PNX-14 exerted protective effects on neurological dysfunction and inflammation in SCI mice through modulating microglial polarization via PTEN/Akt signaling pathway.