Icaritin alleviates docetaxel-induced skin injury by suppressing reactive oxygen species via estrogen receptors.

BACKGROUND: Docetaxel (DTX) exhibits antitumor effects against breast cancer by stabilizing microtubules and increasing the accumulation of reactive oxygen species (ROS). DTX extravasation during infusion often causes skin injury. The present study aimed to investigate the effects and mechanisms of icaritin (ICT) on DTX-induced skin injury. METHODS: The effects of ICT on the viability and apoptosis of HaCaT cells were measured by SRB assay and flow cytometry, respectively. Endogenous LC3 puncta and microtubules were determined by immunofluorescence. The number of mitochondria was measured by MitoTracker orange staining. ROS were determined by dihydroethidium staining. The expression of markers of ROS and autophagy were measured by western blotting. Chloroquine, compound D, and tamoxifen were employed as the inhibitor for autophagy and AMPK, estrogen receptors (ERs) modulator, respectively. RESULTS: DTX inhibited the viability and decreased apoptosis of HaCaT cells, which can be rescued by ICT. ICT decreased microtubule bundles, increased the number of mitochondria, and attenuated ROS of HaCaT cells induced by DTX. ICT blocks autophagy and the autophagic flux. Compound C or tamoxifen diminished the protection effects of ICT on DTX-treated HaCaT cells. CONCLUSION: ICT alleviates DTX-induced skin injury by suppressing ROS, reducing microtubule bundles, and blocking autophagy via ERs. Our study indicated that ICT may be a potential candidate for DTX-induced skin injury.

Icaritin Attenuates Lipid Accumulation by Increasing Energy Expenditure and Autophagy Regulated by Phosphorylating AMPK.

BACKGROUND AND AIMS: Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease, the prevalence of which continues to rise. We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation. METHODS: Cells were treated with icaritin at 0.7, 2.2, 6.7, or 20 µM for 24 h. The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining, respectively. Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining. Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected. The expression levels of proteins in the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway, biomarkers of autophagy, and mitochondria biogenesis were measured by western blotting. LC3 puncta were detected by immunofluorescence. RESULTS: Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells. Icaritin enhanced glucose uptake, decreased adenosine triphosphate content, and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes. Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts. However, icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. CONCLUSIONS: Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.

Naringenin Attenuates Non-Alcoholic Fatty Liver Disease by Enhancing Energy Expenditure and Regulating Autophagy via AMPK.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps growing recently. Purpose: To investigate the effects and mechanisms of naringenin (NAR) on NAFLD. Methods: High-fat diet (HFD)-induced NAFLD rats were orally administered with NAR at 10, 30, and 90 mg/kg for 2 weeks. The serum level of triglyceride (TG), total cholesterol (TC), glutamic-oxaloacetic transaminase (AST), and glutamic-pyruvic transaminase (ALT) was measured. The hepatic histology was detected by H&E and oil red O staining. L02 and Huh-7 cells were induced by sodium oleate to establish a NAFLD cell model. The effects of NAR on lipid accumulation were detected by oil red O staining. The glucose uptake and ATP content of 3T3-L1 adipocytes and C2C12 myotubes were measured. The expression of proteins of the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes was assessed by Western blotting. The mitochondrial biogenesis of 3T3-L1 adipocytes and C2C12 myotubes was measured by mitotracker orange staining and Western blotting. The biomarkers of autophagy were detected by Western blotting and immunofluorescence. The binding of NAR to AMPKγ1 was analyzed by molecular docking. Chloroquine and compound C were employed to block autophagic flux and AMPK, respectively. Results: NAR alleviated HFD-induced NAFLD in rats at 10, 30, and 90 mg/kg. NAR attenuated lipid accumulation in L02 and Huh-7 cells at 0.7, 2.2, 6.7, and 20 µM. NAR increased glucose uptake, decreased the ATP content, activated the CaMKKß/AMPK/ACC pathway, and enhanced the mitochondrial biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. NAR increased autophagy and promoted the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts, while it inhibited autophagy in NAFLD rats, 3T3-L1 adipocytes, and C2C12 myotubes. Molecular docking showed that NAR binds to AMPKγ1. Compound C blocked effects of NAR on lipid accumulation and autophagy in L02 cells. Conclusion: NAR alleviates NAFLD by increasing energy expenditure and regulating autophagy via activating AMPK directly and indirectly. The direct binding of NAR and AMPKγ1 needs further validation.

Temporal and spatial variation in major ion chemistry and source identification of secondary inorganic aerosols in Northern Zhejiang Province, China.

To investigate the seasonal and spatial variations of ion chemistry of fine particles in Northern Zhejiang Province (NZP), China, one year-long field sampling was conducted at four representative sites (two urban, one suburb, and one rural sites) in both cities of Hangzhou and Ningbo from December 2014 to November 2015. Twelve water soluble inorganic ions (WSII) were characterized in this comprehensive study. The annual average of PM2.5 concentration in NZP as overall was 66.2 ± 37.7 µg m-3, and urban sites in NZP were observed with more severe PM2.5 pollution than the suburban and rural sites. The annual average concentration of total WSII at four sampling sites in NZP was 29.1 ± 19.9 µg m-3, dominated by SO42- (10.3 µg m-3), and followed by NO3- (8.9 µg m-3), NH4+ (6.6 µg m-3), Cl- (1.3 µg m-3) and K+ (0.7 µg m-3). Among all cations, NH4+ was the predominant neutralizing ion with the highest neutralization factor (NF), while the remaining cations showed limited neutralization capacity. The highest and lowest sulfur oxidation ratio (SOR) values in this region were found in summer and winter, respectively; while the seasonal patterns for nitrogen oxidation ratio (NOR) were opposite to that of SOR. Principal component analysis (PCA) showed that the significant sources of WSII in NZP were industrial emissions, biomass burning, and formation of secondary inorganic aerosols. In addition, contribution from transboundary transport of polluted aerosols was also confirmed from the assessment through air mass backward trajectory analysis.

Radicals and molecular products from the gas-phase pyrolysis of lignin model compounds. Cinnamyl alcohol.

The experimental results on detection and identification of intermediate radicals and molecular products from gas-phase pyrolysis of cinnamyl alcohol (CnA), the simplest non-phenolic lignin model compound, over the temperature range of 400-800 °C are reported. The low temperature matrix isolation - electron paramagnetic resonance (LTMI-EPR) experiments along with the theoretical calculations, provided evidences on the generation of the intermediate carbon and oxygen centered as well as oxygen-linked, conjugated radicals. A mechanistic analysis is performed based on density functional theory to explain formation of the major products from CnA pyrolysis; cinnamaldehyde, indene, styrene, benzaldehyde, 1-propynyl benzene, and 2-propenyl benzene. The evaluated bond dissociation patterns and unimolecular decomposition pathways involve dehydrogenation, dehydration, 1,3-sigmatropic H-migration, 1,2-hydrogen shift, C-O and C-C bond cleavage processes.

Radicals from the gas-phase pyrolysis of a lignin model compound: p-coumaryl alcohol.

The intermediate radicals produced in the gas-phase pyrolysis of one of the main building blocks of lignin - p-coumaryl alcohol (p-CMA) - were investigated using the low temperature matrix isolation technique interfaced with electron paramagnetic resonance spectroscopy (LTMI-EPR). An anisotropic EPR spectrum characterized by a high g-value (>2.0080) and a relatively low saturation coefficient (∼1.40) throughout the high pyrolytic temperature region (700 to 1000 °C) was observed. Theoretical calculations revealed plausible decomposition pathways for p-CMA comprising highly delocalized aromatic radicals. The results provide evidence for a dominant role of oxygen-centered radicals during the pyrolysis of p-CMA.

Megalobrama amblycephala cardiac troponin T variants: molecular cloning, expression and response to nitrite.

Cardiac troponin T (TNNT2), as a member of troponin superfamily, plays important roles during early cardiogenesis, and contraction and relaxation of myocardial cells. In this study, two alternatively spliced variants of Megalobrama amblycephala TNNT2 were identified showing a difference of 19 amino acids in the N-terminal hypervariable region. The longer cDNA (TNNT2-1) was 1,118 bp, encoding 284 amino acid residues, contained conserved central tropomyosin-binding region, cardiac specific signal and C-terminal segments except the N-terminal hypervariable region. The TNNT2 transcripts first appeared at 16 hours post-fertilization (hpf) peaking at 28 hpf (onset of heartbeat). In addition, strong expression of TNNT2 was found in the cardiac muscle. After nitrite exposure, the increased TNNT2 expression levels in the heart indicated that nitrite might induce cardiac injury. Results of semi-quantitative RT-PCR indicated that the two alternatively spliced variants existed in early development stages since their first appearance at 16 hpf and heart, spleen, headkiney of M. amblycephala. The shorter transcript (TNNT2-2) was proved to be dominant in the embryos and heart of M. amblycephala, furthermore, the increase of TNNT2 expression level in the heart after nitrite exposure was mainly caused by TNNT2-2.

Gas/particle partitioning of atmospheric PCDD/Fs in a satellite town in Eastern China.

Gas/particle partitioning of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in ambient air was investigated in a satellite town in Eastern China from April 2007 to January 2008 comprehending large temperature variations (from 3 to 34 degrees C, daily average). Molecular weight, molecular structure and ambient temperatures are the three major factors that govern the gas/particle partitioning of atmospheric PCDD/Fs throughout the year. Generally, good agreements were obtained (except for winter) between measured particulate fractions and theoretical estimates of both the Junge-Pankow adsorption model and Harner Bidleman absorption model using different sets of subcooled liquid vapor pressure (P(L)(o)) and octanol-air partition coefficient (K(oa)), respectively. Models utilizing P(L)(o) estimates, derived from gas chromatographic retention indices (GC-RIs), are more accurate than that of entropy-based. Moreover, during winter, the K(oa)-based model using the GC-RIs approach performs better on lower chlorinated PCDD/Fs than that of P(L)(o)-based. Furthermore, possible sources of mismatch between measured and predicted values in winter (3-7 degrees C) were discussed. Gas adsorption artifact was demonstrated to be of minor importance for the phenomena observed. On the other hand, large deviations of slopes (m(r)) and intercepts (b(r)) in logK(p) vs. logP(L)(o)(Pa)/logK(oa) plots from theoretical values are observed in the literature data and these are found to be linearly correlated with ambient temperatures (P<0.001) in this study. This indicates that the non-equilibrium partitioning of PCDD/Fs in winter may be significantly influenced by the colder temperatures that may have slowed down the exchange between gaseous and particulate fractions.

Concentrations, profiles, and sources of atmospheric PCDD/Fs near a municipal solid waste incinerator in Eastern China.

Ambient air monitoring of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) was performed to investigate their concentrations, profiles, and sources near a municipal solid waste incinerator (MSWI) in Eastern China. The PCDD/F concentrations varied over a factor of 51.4 from 0.059 to 3.03 pg I-TEQ m(-3) (or over 41.4 from 3.96 to 164 pg m(-3)) and fell at the higher end of the range in recorded peer investigations around the world. Almost all ambient air samples show a unique TCDF-dominanthomologue pattern, characterized by decreasing concentrations with increasing levels of chlorination (except for OCDD). By contrast, the dominant congener in terms of concentration profiles shows temporal and spatial variations among the OCDD, OCDF, and 1,2,3,4,6,7,8-HpCDF. The results from a congener-specific factor analysis between ambient air and PCDD/F emission sources, as well as U.S. EPA Chemical Mass Balance (CMB8.2) and Industrial Source Complex Short Term Version 3 (ISCST3) modeling, suggest that the deterioration of air quality in the study area is primarily attributed to open burning of wastes (OB), followed by hot water boilers (HWBs), traffic, and the MSWI.

Agricultural soil monitoring of PCDD/Fs in the vicinity of a municipal solid waste incinerator in Eastern China: temporal variations and possible sources.

The temporal variations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in 33 agricultural soil samples in the vicinity of a municipal solid waste incinerator (MSWI) in Eastern China were determined one year after the initial investigation in 2006. The soil PCDD/F concentrations in 2007 ranged from 73.6 to 377 ng kg(-1) (0.60-6.38 ng I-TEQ kg(-1)). During 2006-2007, the overall soil PCDD/F levels increased significantly, i.e., 33% and 39% for total concentration and I-TEQ (median value), respectively. Moreover, soils in the study area are proved to be almost free from previously suspected PCDD/F sources, i.e., pentachlorophenol/sodium penta-chlorophenate (PCP/PCP-Na) and 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP) contaminations. Furthermore, the results from a congener-specific factor analysis between soils (collected in two investigations) and dioxin emission sources suggest that diffuse sources including open burning of wastes, traffic and hot water boilers are major contributors that are responsible for the accumulation of PCDD/Fs in soils. By contrast, the impact of the presumably major PCDD/F source identified in our previous study, i.e., the MSWI, seems to be limited.

Source identification of PCDD/Fs in agricultural soils near to a Chinese MSWI plant through isomer-specific data analysis.

Isomer-specific data were investigated in order to identify the sources of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in agricultural soils, including Fluvo-aquic and paddy soils, in the vicinity of a Chinese municipal solid waste incineration (MSWI) plant. Homologue and isomer profiles of PCDD/Fs in soils were compared with those of potential sources, including combustion sources, i.e., MSWI flue gas and fly ash; and the impurities in agrochemicals, such as the pentachlorophenol (PCP), sodium pentachlorophenate (PCP-Na) and 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP). The results showed that the PCDD/F isomer profiles of combustion sources and agricultural soils were very similar, especially for PCDFs, although their homologue profiles varied, indicating that all the isomers within each homologue behave identically in the air and soil. Moreover, factor analysis of the isomer compositions among 33 soil samples revealed that the contamination of PCDD/Fs in agricultural soils near the MSWI plant were primarily influenced by the combustion sources, followed by the PCP/PCP-Na and CNP sources. This implication is consistent with our previous findings based on chemometric analysis of homologue profiles of soil and flue gas samples, and identifies PCP/PCP-Na as an additional important source of PCDD/Fs in the local area. This makes the similarities and differences of isomer profiles between Fluvo-aquic and paddy soils more explainable. It is, therefore, advisable to use isomer-specific data for PCDD/F source identifications where possible.