Publications by authors named "Yongjie Wei"

71 Publications

The changes of essential trace elements in residents from an e-waste site and the relationships between elements and hormones of the hypothalamic-pituitary-thyroid (HPT) axis.

Ecotoxicol Environ Saf 2021 Oct 15;222:112513. Epub 2021 Jul 15.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

The heavy metals pollution and related health issues were widely reported in e-waste sites, while the impacts of e-waste exposure on the essential trace elements have been neglected. The aim of this study was focused on the internal Cu, Fe, Mn and Zn levels in the residents from an e-waste site and the potential endocrine disrupting effects of these essential trace elements on the hypothalamic-pituitary-thyroid (HPT) axis. This was a cross-sectional study that 87 subjects were recruited from the e-waste site and 81 from the reference site. The results indicated that the e-waste exposed group had significantly lower Fe, Mn level when compared with the reference group (p < 0.05). Cu and Zn were also lower in the exposed group but the differences were not statistically significant. The exposed group had significantly higher TSH level and Fe was significantly associated with TSH in the females (β (95% CI): - 1.892 (-3.309, -0.475), p = 0.009), rather than in males or all subjects. The exposed group also showed oxidative stress which was indicated by the increased concentrations of MDA and 8-iso-PG. It was further indicated the elevated MDA was mediated by the increase of TSH in the females but not directly related to Fe. In conclusion, the e-waste exposed group showed a decrease of essential trace elements, an increase of TSH and oxidative stress. The decreased Fe was related to the elevated TSH in the females, which further indirectly mediated the increase of oxidative stress. The results suggested that the internal exposure levels and the potential health effects of the essential trace elements in populations from e-waste sites should be of more concern. And the women might be more vulnerable and they need more protection to against the adverse health effects from e-waste.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112513DOI Listing
October 2021

Previously identified and unidentified polybrominated biphenyl congeners in serum from people living in an electronic waste dismantling area in China.

Chemosphere 2021 Sep 8;279:130478. Epub 2021 Apr 8.

College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Engineering Research Center of Food Environment and Public Health, Beijing, 100081, China. Electronic address:

The effects of polybrominated biphenyls (PBBs) on human health have previously attracted much attention, but recent studies of PBBs have been focused on BB-153 and a few other congeners. PBB concentrations in serum samples from residents of an area containing an electronic waste dismantling site were determined in this study. The total PBB concentrations (i.e., the sums of the concentrations of the 35 PBB congeners) were 229-1360 ng/g lipid. The BB-153 concentrations were markedly higher in the samples from people living in the electronic waste dismantling area than in samples from people living in a nearby control area. BB-153 was found in all of the samples from the study exposure area but the concentrations were relatively low (0.07-4.70 ng/g lipid). High BB-1 concentrations were found for the first time in serum from people living in both the electronic waste dismantling and control areas. The BB-1 concentrations were 211-1280 ng/g lipid. The retention times of the 35 PBB standards and PCBs (polychlorinated biphenyls) with similar structures were used to predict the retention times of unidentified PBB congeners to allow the PBB distributions in the serum samples to be identified. A total of 26 previously unidentified PBB congeners were identified in the human serum samples. BB-5, BB-35, BB-79, and BB-109 were found in >50% of the samples. The PBB patterns in the serum samples were different from the patterns previously found in serum after a PBB contamination incident in 1973, so the health risks currently posed by PBBs are worth studying.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.130478DOI Listing
September 2021

The Role of Autophagy in Skeletal Muscle Diseases.

Front Physiol 2021 25;12:638983. Epub 2021 Mar 25.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.

Skeletal muscle is the most abundant type of tissue in human body, being involved in diverse activities and maintaining a finely tuned metabolic balance. Autophagy, characterized by the autophagosome-lysosome system with the involvement of evolutionarily conserved autophagy-related genes, is an important catabolic process and plays an essential role in energy generation and consumption, as well as substance turnover processes in skeletal muscles. Autophagy in skeletal muscles is finely tuned under the tight regulation of diverse signaling pathways, and the autophagy pathway has cross-talk with other pathways to form feedback loops under physiological conditions and metabolic stress. Altered autophagy activity characterized by either increased formation of autophagosomes or inhibition of lysosome-autophagosome fusion can lead to pathological cascades, and mutations in autophagy genes and deregulation of autophagy pathways have been identified as one of the major causes for a variety of skeleton muscle disorders. The advancement of multi-omics techniques enables further understanding of the molecular and biochemical mechanisms underlying the role of autophagy in skeletal muscle disorders, which may yield novel therapeutic targets for these disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.638983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027491PMC
March 2021

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BMC Biol 2021 04 8;19(1):67. Epub 2021 Apr 8.

Terrestrial Wildlife Rescue and Epidemic Diseases Surveillance Center of Guangxi, Nanning, Guangxi, 530003, China.

Background: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche.

Results: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies.

Conclusions: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12915-021-00998-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034193PMC
April 2021

Assessing Approaches of Human Inhalation Exposure to Polycyclic Aromatic Hydrocarbons: A Review.

Int J Environ Res Public Health 2021 03 18;18(6). Epub 2021 Mar 18.

Institute of Nature and Environmental Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

Polycyclic aromatic hydrocarbons (PAHs) are a class of important organic pollutants widely emitted from anthropogenic activities, with a general distribution in the gas and particulate phases. Some PAHs are carcinogenic, teratogenic, and mutagenic. Inhalation exposure to PAHs is correlated with adverse health outcomes in the respiratory and cardiovascular systems. Thus, it is significant to determine the exposure level of the general population. This study summarizes the evaluation methods for PAH exposure, focusing on different exposure parameters. External exposure can be determined via the collection of the environmental pollution concentration through active samplers or passive samplers during environmental monitoring or personal sampling. Time-activity patterns give critical exposure information that captures the exposure period, origin, and behaviors. Modeling is a labor-less approach for human exposure estimation, and microenvironmental exposure requires specific research. It is important to select appropriate methods to quantify the exposure level to provide accurate data to establish the exposure-risk relationship and make scientific suggestions for the protection of public health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18063124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003068PMC
March 2021

Cobalt exposure increases the risk of fibrosis of people living near E‑waste recycling area.

Ecotoxicol Environ Saf 2021 Jun 17;215:112145. Epub 2021 Mar 17.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Center for Global Health, School of Public Health, Nanjing Medical University, China. Electronic address:

The toxicity of heavy metals is one of the major public health issues leading to hazardous effects on humans. Many studies focus on the adverse effects on people who were working in or living near E-waste recycling. However, little is known to the sustaining effects of E-waste exposure on human health after the recycling factories were shut down. In the present study, we collected the blood of people living near E‑waste recycling facilities after the recycling factories were closed for 2 years. Eight heavy metals were examined in all blood samples. The results revealed that the blood levels of lead (Pb), nickel (Ni), cobalt (Co), mercury (Hg) were significantly higher in the exposed group than in the reference group, and no difference was observed for copper (Cu), zinc (Zn), stannum (Sn), cadmium (Cd). Transforming growth factor-β (TGF-β) and alpha-smooth muscle actin (α-SMA) were analyzed as the important indicators of fibrosis, which were statistically significantly higher in the exposed group than in the reference group. 8-isoprostane (8-I) and malondialdehyde (MDA) as the biomarkers of oxidative stress (OS) were elevated in the exposed group. Furthermore, both Spearman correlation and multiple linear regression showed that Co was positively correlated with TGF-β, α-SMA and 8-I in the exposed group. Accordingly, we speculate that high concentrations of Co dissolved in the blood may increase the risk of tissue fibrosis through stimulating myofibroblast activation and OS involve in the process, which may provide some potential new hints for the intervention for tissue fibrosis in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112145DOI Listing
June 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

High concentration of blood cobalt is associated with the impairment of blood-brain barrier permeability.

Chemosphere 2021 Jun 7;273:129579. Epub 2021 Jan 7.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; Center for Global Health, School of Public Health, Nanjing Medical University, China. Electronic address:

Excess heavy metals can lead to many kinds of adverse effects in human. The present study is designed to investigate whether the internal excess burden of heavy metals relate to the disturbance of the Blood-brain-barrier (BBB) and oxidative stress (OS) in subjects, and identify specific metallic constituents responsible for the disturbance. We collected the blood from recruited 122 subjects for our comparison study, 69 were living at an area near e-waste dismantling factories (exposed group), who have higher levels of heavy metals in the body; and others were in a chosen reference area (reference group), who were the general residents in city, in December 2017 in Taizhou, Zhejiang province. The analyses showed that the concentrations of altogether 4 metals, including nickel (Ni), cobalt (Co), mercury (Hg) and stannum (Sn), and the triggers of BBB disruption (Apolipoprotein E4 and matrix-metalloproteinase-9), indicators of BBB (Myelin basic protein, serotonin and dopamine) and biomarkers of OS (Malondialdehyde and 8-isoprostane) were statistically significant higher in exposed group than in reference group. Moreover, they are also significantly positively correlated with each other. Among all the metals, both Pearson correlation and multiple linear regression showed Co was positive correlated with almost all biomarkers. Considering the explicit correlation between Co and BBB permeability, we speculated that high burden of Co in blood may have a connection with neurodegenerative diseases, which propose a requirement for constructing the environmental criteria for Co and might provide a potential new hint for the intervention of dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.129579DOI Listing
June 2021

Uptake and distributions of polycyclic aromatic hydrocarbons in cultivated plants around an E-waste disposal site in Southern China.

Environ Sci Pollut Res Int 2021 Jan 5;28(3):2696-2706. Epub 2020 Sep 5.

Chinese Research Academy of Environmental Science, Beijing, 100012, China.

Polycyclic aromatic hydrocarbons (PAHs) in air, soil, and cultivated plants at e-waste disposal sites in Taizhou, Zhejiang Province, were determined to allow PAH uptake by and distributions in plants to be investigated. The PAH distributions in air, rhizosphere soil, and surface soil were markedly different. This indicated that root morphology variations and root exudates may affect PAH compositions in soil around plants. The PAH concentrations in the plant samples were 29.7-2170 ng/g. The lowest PAH concentration was found in a peeled taproot sample. The PAH concentration gradients from the plant shoots to roots suggested that PAHs entered the plants through various pathways. The three- and four-ring PAHs were found to be absorbed more readily than the higher-molecular-weight (five- and six-ring) PAHs. This indicated that high-molecular-weight PAHs in soil can be prevented from entering plants, particularly taproots, via root exudates and the root peel. For most plants, the highest PAH concentrations were found in leaves, indicating that atmospheric deposition may strongly affect PAH concentrations in aerial plant parts. High-molecular-weight PAHs are more readily absorbed from ambient air by leaves than other parts. Lower PAH concentrations were found in fruits than other plant parts. This and the differences in PAH distributions between fruits and other aerial parts indicated that PAHs may be selectively absorbed by fruits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-10642-1DOI Listing
January 2021

The sustaining effects of e-waste-related metal exposure on hypothalamus-pituitary-adrenal axis reactivity and oxidative stress.

Sci Total Environ 2020 Oct 5;739:139964. Epub 2020 Jun 5.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Center for Global Health, School of Public Health, Nanjing Medical University. Electronic address:

Taizhou is one of the three largest electronic waste (e-waste) recycling locations in China. At present, to prevent the environmental problems stem from e-waste dismantling, the local government shut down all the industries in 2015. However, little is known to the sustaining effects of e-waste exposure on human health after the e-waste recycling factories were closed. In this study, we collected blood samples in the residents living near e-waste dismantling factories (exposed group) and a chosen reference area (reference group) for comparison in Taizhou in December 2017.17 metals were quantitatively determined in all blood samples. Among them, the concentrations of altogether 9 metals, including chromium (Cr), arsenic (As), cobalt (Co), nickel (Ni), silver (Ag), stannum (Sn), mercury (Hg), lanthanum (La) and cerium (Ce) were significant higher in the individuals in exposed group than in reference group. Hypothalamus-pituitary-adrenal axis (HPA axis) is critical endocrine system in regulating many physical functions. We found that the concentrations of hormones in HPA axis, including corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, were higher in exposed group than in reference group. Moreover, we also observed significantly higher concentrations of biomarkers of oxidative stress (OS), including malondialdehyde (MDA) and 8-isoprostane (8-I), in exposed group compared with reference group even though the e-waste industries have been shut down for over 2 years. Meanwhile, the hormones in the HPA axis and the biomarkers of OS showed sinificantly positive correlation. The results of Pearson correlation and multiple linear regression showed that blood Cr and Ni positively correlated with the 3 hormones and 2 biomarkers of OS. Considering the relationship between Ni and Cr, HPA axis, OS, we speculated that high concentrations of Cr and Ni exposure could induce oxidative damage in e-waste exposure persons, and the regulations of HPA axis could play the important role during the process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.139964DOI Listing
October 2020

Improved Osteogenesis of Selective-Laser-Melted Titanium Alloy by Coating Strontium-Doped Phosphate With High-Efficiency Air-Plasma Treatment.

Front Bioeng Biotechnol 2020 12;8:367. Epub 2020 May 12.

Department of Orthopedics, The Second Hospital, Jilin University, Changchun, China.

Surface treatment and bioactive metal ion incorporation are effective methods for the modification of titanium alloys to be used as biomaterials. However, few studies have demonstrated the use of air-plasma treatment in orthopedic biomaterial development. Additionally, no study has performed a direct comparison between unmodified titanium alloys and air-plasma-treated alloys with respect to their biocompatibility and osteogenesis. In this study, the biological activities of unmodified titanium alloys, air-plasma-treated titanium alloys, and air-plasma-treated strontium-doped/undoped calcium phosphate (CaP) coatings were compared. The strontium-doped CaP (Sr-CaP) coating on titanium alloys were produced by selective laser melting (SLM) technology as well as micro-arc oxidation (MAO) and air-plasma treatment. The results revealed that rapid air-plasma treatment improved the biocompatibility of titanium alloys and that Sr-CaP coating together with air-plasma treatment significantly enhanced both the biocompatibility and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Overall, this study demonstrated that low temperature air-plasma treatment is a fast and effective surface modification which improves the biocompatibility of titanium alloys. Additionally, air-plasma-treated Sr-CaP coatings have numerous practical applications and may provide researchers with new tools to assist in the development of orthopedic implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2020.00367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235326PMC
May 2020

Comparison of Transcriptomics Changes Induced by TCS and MTCS Exposure in Human Hepatoma HepG2 Cells.

ACS Omega 2020 May 6;5(19):10715-10724. Epub 2020 May 6.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

Triclosan (TCS) has been a widely used antibacterial agent in medical and personal care products in the last few decades. Methyl TCS (MTCS) is the major biotransformation product of TCS through replacement of the hydroxyl group with methoxy. Previous studies revealed that MTCS showed reduced toxicity but enhanced environmental persistence, when compared with TCS. Till date, the toxicological molecular mechanisms of TCS and MTCS remain to be clarified. This study aimed to investigate the transcriptomic changes in HepG2 cells induced by TCS and MTCS using microarray chips and to identify key target genes and related signal pathways. The microarray data showed that there were 1664 and 7144 differentially expressed genes (DEGs) in TCS- and MTCS-treated groups, respectively. Gene ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) analysis revealed that TCS and MTCS induced overlapping as well as distinct transcriptome signatures in HepG2 cells. Both TCS and MTCS could result in various biological responses in HepG2 cells mainly responding to biosynthetic and metabolic processes but probably through different regulatory pathways. Among the selected 50 GO terms, 9 GO terms belonging to the cellular component category were only enriched in the MTCS group, which are mainly participating in the regulation of cellular organelle's function. KEGG analysis showed that 19 and 59 pathway terms were separately enriched in TCS and MTCS groups, with only seven identical pathways. The selected 10 TCS-specific signal pathways are mainly involved in cell proliferation and apoptosis, while the selected 10 MTCS-specific pathways mainly take part in the regulation of protein synthesis and modification. The overall data suggested that MTCS induced more enriched DEGs, GO terms, and pathway terms than TCS. In conclusion, compared with TCS, MTCS presents lower polarity and stronger lipophilicity, enabling MTCS to cause more extensive transcriptomic changes in HepG2 cells, activate differentiated signal pathways, and finally lead to differences in biological responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240827PMC
May 2020

Influence of metals from e-waste dismantling on telomerelength and mitochondrial DNA copy number in people living near recycling sites.

Environ Int 2020 07 10;140:105769. Epub 2020 May 10.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Center for Global Health, School of Public Health, Nanjing Medical University, China. Electronic address:

Metals are the primary toxicants released by electronic waste (e-waste) recycling, but their adverse effects on people working in e-waste recycling or living near e-waste sites have not been studied well. Taizhou is one of the three largest e-waste recycling locations in China. Atpresent, to prevent the environmental problems stem from e-waste dismantling, the local government has shut down all the industries in 2015. In this study, we collected blood samples of residents living near e-waste dismantling factories, and in matched reference areas in Taizhou, in December 2017, after the factories have been shut down for two years. Seventeen metals were quantified in all blood samples. Among them, the concentrations of arsenic (As), nickel (Ni), silver (Ag), lanthanum (La), and Cerium (Ce) were statistically significant higher in individuals in e-waste recycling locations than those in reference location. Length of telomere (LOT) and mitochondrialDNA copy number (MCN) were measured in blood as a marker of human health. In the e-waste dismantling location, the level LOT and MCN were elevated in resident living near e-waste sites (RE) and former working in e-waste recycling (OE) than residents living in the reference area (RF). Furthermore, Pearson correlation and multiple linear regression analysis between the changed metals and LOT, MCN in blood were performed. In RE and OE, the concentration of Ni significantly positively correlated with MCN; in OE, the Ni level significantly positively correlated with MCN and LOT. Considering that the high level of Ni, TL and mtDNA were correlated with the risk of cancer, we speculated that e-waste exposure elevate the risk of cancer, and Ni that has long been present in the body was the potential hazardous element causing cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105769DOI Listing
July 2020

PDK1 regulates the survival of the developing cortical interneurons.

Mol Brain 2020 05 4;13(1):65. Epub 2020 May 4.

Key Laboratory of Developmental Genes and Human Diseases, MOE, School of Medicine, Southeast University, Nanjing, 210009, China.

Inhibitory interneurons are critical for maintaining the excitatory/inhibitory balance. During the development cortical interneurons originate from the ganglionic eminence and arrive at the dorsal cortex through two tangential migration routes. However, the mechanisms underlying the development of cortical interneurons remain unclear. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been shown to be involved in a variety of biological processes, including cell proliferation and migration, and plays an important role in the neurogenesis of cortical excitatory neurons. However, the function of PDK1 in interneurons is still unclear. Here, we reported that the disruption of Pdk1 in the subpallium achieved by crossing the Dlx5/6-Cre-IRES-EGFP line with Pdk1 mice led to the severely increased apoptosis of immature interneurons, subsequently resulting in a remarkable reduction in cortical interneurons. However, the tangential migration, progenitor pools and cell proliferation were not affected by the disruption of Pdk1. We further found the activity of AKT-GSK3β signaling pathway was decreased after Pdk1 deletion, suggesting it might be involved in the regulation of the survival of cortical interneurons. These results provide new insights into the function of PDK1 in the development of the telencephalon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13041-020-00604-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197138PMC
May 2020

Natural aeolian dust particles have no substantial effect on atmospheric polycyclic aromatic hydrocarbons (PAHs): A laboratory study based on naphthalene.

Environ Pollut 2020 Aug 31;263(Pt A):114454. Epub 2020 Mar 31.

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Institute of Nature and Environmental Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address:

Natural aeolian dust (AD) particles are potential carriers of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere. The heterogeneous interaction between them may lead to worsened air quality and enhanced cytotoxicity and carcinogenicity of ambient particulates in downwind areas, and this topic requires in-depth exploration. In this study, AD samples were collected from four Asian dust sources, and their physical properties and compositions were determined, showing great regional differences. The physical and chemical interactions of different AD particles with naphthalene (Nap; model PAH) were observed in aqueous systems. The results showed that AD particles from the Loess Plateau had weak adsorption to Nap, which was fitted by the Langmuir isotherm. There was no obvious adsorption to Nap found for the other three AD samples. This difference seemed to depend mainly on the specific surface area and/or the total pore volume. In addition, the Nap in the aqueous solution did not undergo chemical reactions under dark conditions and longwave ultraviolet (UV) radiation but degraded under shortwave UV radiation, and 2-formylcinnamaldehyde and 1,4-naphthoquinone were the first-generated products. The degradation of Nap in the aqueous solution was probably initiated by photoionization, and the reaction rate constant (between 1.44 × 10 min and 8.55 × 10 min) was much lower than that of Nap with hydroxyl radicals. Instead of inducing or promoting the chemical change in Nap, the AD particles slowed photodegradation due to the extinction of radiation. Therefore, it is inferred that natural AD particles have no substantial effect on the transportation and transformation of PAHs in the atmosphere.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114454DOI Listing
August 2020

Rare earth elements exposure and the alteration of the hormones in the hypothalamic-pituitary-thyroid (HPT) axis of the residents in an e-waste site: A cross-sectional study.

Chemosphere 2020 Aug 13;252:126488. Epub 2020 Mar 13.

Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China. Electronic address:

Rare earth elements (REEs) are widely used in electronic products. But the contaminations of REEs in the e-waste sites and the related health effects were barely investigated. In the present study, we analyzed the concentrations of REEs and the hormones of the HPT axis in plasma of subjects recruited from an e-waste area and a reference area in Taizhou, China. The results showed that the concentrations of several REEs like La, Ce were much higher in the exposed group than in the control group (all p < 0.001). The thyroid hormones, FT3 and FT4, and TRH showed no significant difference between the two groups, while the concentration of TSH was significantly higher in the exposed group when compared to the control group (p = 0.002). Separate regression analysis indicated that elevated La and Ce levels were associated with higher TSH concentrations. MDA and 8-iso, the biomarkers of oxidative stress, were also significantly higher in the exposed group than that of the control group (p = 0.002 and p = 0.003, respectively). The increased oxidative stress might be the mechanism underlying the disruptive effects of REEs on TSH. Our results indicated that the quantities of internal exposure of REEs in the subjects in the e-waste area were considerable and the compositional profile of the REEs in the exposed group was different from the control group due to the e-waste dismantling. The expression of TSH were also affected by high La and Ce exposure which showed an endocrine disruption effects of REEs on HPT axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.126488DOI Listing
August 2020

Characteristics of Polycyclic Aromatic Hydrocarbons (PAHs) and Common Air Pollutants at Wajima, a Remote Background Site in Japan.

Int J Environ Res Public Health 2020 02 4;17(3). Epub 2020 Feb 4.

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

: Background sites are mainly affected by long-range-transported air pollutants, resulting in potential adverse effects on local atmospheric environments. A 4-5 year observational study was conducted to illustrate the air pollution profile at the Kanazawa University Wajima air monitoring station (KUWAMS), an ideal remote background site in Japan. : Nine polycyclic aromatic hydrocarbons (PAHs) in the particulate phase and various air pollutants were continuously monitored for 4-5 years. Diagnostic ratios of PAHs and back-trajectory analysis were applied to trace the possible sources of the air pollutants collected at the sampling site. : The atmospheric concentration of PAHs in the atmosphere at the site decreased from 2014 to 2019, benefit from the predominant air pollution control policy in China and Japan. Common air pollutants including sulfur dioxide (SO), nitrogen oxides (NO), ozone, methane (CH), and non-methane hydrocarbon (NMHC) were detected in low concentrations from 2016 to 2019, while ozone (O) and particulate matter (PM, PM with a diameter less than 2.5 μm) were present in high levels that exceeded the Japanese standards. Most air pollutants peaked in spring and showed evident diurnal variations in spring and summer. : This is the first study to clarify the atmospheric behaviors of multiple air pollutants at a background site in Japan. Significant external air pollutant impact and unneglectable air pollution were demonstrated at KUWAMS, indicating the importance of studying atmospheric pollution at remote sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17030957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036938PMC
February 2020

Associations between metal exposure and global DNA methylation in potentially affected people in E-Waste recycling sites in Taizhou City, China.

Sci Total Environ 2020 Apr 23;711:135100. Epub 2019 Nov 23.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Center for Global Health, School of Public Health, Nanjing Medical University, China. Electronic address:

Electronic waste (e-waste) has been an emerging environmental health issue, and it has already provoked all aspects of attention. Taizhou is one of the three largest e-waste recycling locations in China. Atpresent, to prevent the environmental problems stem from e-waste dismantling, the local government has shut down all the industries in 2015. In this study, we collected blood samples of residents living near e-waste dismantling factories, and in matched reference areas in Taizhou, in December 2017, after the factories have been shut down for two years. Twenty-five metals were quantified in all blood samples. Among them, the concentrations of As, Ni, Ag, La, and Ce were statistically significant higher in individuals in e-waste recycling locations than those in reference location. Global DNA methylation was measured in blood as a marker of human health. Pearson correlation and multiple linear regression analysis between the changed metals and global DNA methylation in blood were performed. The result showed that only blood Ce was negatively correlated with global DNA methylation level significantly in pre-workers exposed e-waste workers (r = -0.51, p = 0.01). Our findings indicated that high concentrations of exposure to Ce in e-waste dismantling site could have sustained effects on the DNA methylation in blood although the e-waste industry had been closed for 2 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.135100DOI Listing
April 2020

PM-bound polycyclic aromatic hydrocarbons and nitro-polycyclic aromatic hydrocarbons inside and outside a primary school classroom in Beijing: Concentration, composition, and inhalation cancer risk.

Sci Total Environ 2020 Feb 2;705:135840. Epub 2019 Dec 2.

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Institute of Nature and Environmental Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address:

PM samples were collected inside and outside a primary school classroom in Beijing in 2015 and analysed for 11 polycyclic aromatic hydrocarbons (PAHs) and 10 nitro-PAHs (NPAHs). In the sampling period in the heating season (namely, the heating period), the median concentrations of indoor and outdoor PAHs were 223 ng/m and 264 ng/m, respectively, and those of indoor and outdoor NPAHs were 3.61 ng/m and 5.12 ng/m, respectively. The concentrations of PAHs and NPAHs were consistently higher in the heating period than those (indoor PAHs: 8.75 ng/m, outdoor PAHs: 8.95 ng/m, indoor NPAHs: 0.25 ng/m, outdoor NPAHs: 0.40 ng/m) in the sampling period in the non-heating season (namely, the non-heating period). In both periods, total PAHs and total NPAHs in indoor PM, as well as most individual PAHs and NPAHs, were positively correlated with the outdoor PAH and NPAH concentrations (p < 0.05). This finding suggests that indoor PAHs and NPAHs are largely dependent on outdoor inputs. It is inferred from the diagnostic ratios that PAHs and NPAHs in indoor and outdoor PM were affected jointly by coal combustion and vehicular emission in the heating period and mainly derived from vehicle exhaust in the non-heating period. Both indoor and outdoor PM showed considerable benzo[a]pyrene equivalent toxicity (BaP), especially in the heating period. Benzo[c]fluorene (BcFE) had relatively low concentrations but large contributions to BaP in both periods. This is the first report of PM-bound BcFE inside and outside classrooms in Beijing. This result indicates that neglecting PAHs with low abundance but high toxicity leads to a significant underestimation of the overall PAH toxicity. The inhalation cancer risk (CR) of PAHs and NPAHs in PM during the primary school year exceeded the acceptable level as defined by the U.S. EPA, emphasizing its impact on the lifetime CR in schoolchildren.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.135840DOI Listing
February 2020

Size distribution of particulate polycyclic aromatic hydrocarbons in fresh combustion smoke and ambient air: A review.

J Environ Sci (China) 2020 Feb 16;88:370-384. Epub 2019 Sep 16.

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Institute of Nature and Environmental Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the atmosphere and they mostly stem from the imperfect combustion of fossil fuels and biofuels. PAHs are inherently associated with homogenous fine particles or distributed to different-sized particles during the aging of air masses. PAHs carried by fine particles undergo a long-range transport to remote areas while those adsorbed on coarse particles have a shorter lifetime in ambient air. More importantly, PAHs with higher molecular weights tend to be bound with finer particles and can deeply enter the lungs, posing severe health risks to humans. Thus, the environmental fate and health effects of particulate PAHs are strongly size-dependent. This review summarizes the size distributions of particulate PAHs freshly emitted from combustion sources as well as the distribution patterns of PAHs in ambient particles. It was found that PAHs from stationary sources are primarily bound to fine particles, which are slightly larger than particles to which PAHs from mobile sources are bound. In ambient air, particulate PAHs are distributed in larger size modes than those in the combustion fume, and the particle size decreases with PAH molecular weight increasing. The relevant mechanisms and influencing factors of particle size distribution changes are illustrated in this article, which are essentially attributed to combustion and ambient temperature as well as the physical and chemical properties of PAHs. Overall, the study on the particle size distribution of PAHs will contribute for a full understanding of the origin, atmospheric behaviors and health effects of particulate PAHs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jes.2019.09.007DOI Listing
February 2020

Ozone Pollution: A Major Health Hazard Worldwide.

Front Immunol 2019 31;10:2518. Epub 2019 Oct 31.

Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China.

Oxides of nitrogen (NO) and volatile organic compounds (VOCs) released into the atmosphere can react in the presence of solar irradiation, leading to ozone formation in the troposphere. Historically, before clean air regulations were implemented to control NO and VOCs, ozone concentrations were high enough to exert acute effects such as eye and nose irritation, respiratory disease emergencies, and lung function impairment. At or above current regulatory standards, day-to-day variations in ozone concentrations have been positively associated with asthma incidence and daily non-accidental mortality rate. Emerging evidence has shown that both short-term and long-term exposures to ozone, at concentrations below the current regulatory standards, were associated with increased mortality due to respiratory and cardiovascular diseases. The pathophysiology to support the epidemiologic associations between mortality and morbidity and ozone centers at the chemical and toxicological property of ozone as a strong oxidant, being able to induce oxidative damages to cells and the lining fluids of the airways, and immune-inflammatory responses within and beyond the lung. These new findings add substantially to the existing challenges in controlling ozone pollution. For example, in the United States in 2016, 90% of non-compliance to the national ambient air quality standards was due to ozone whereas only 10% was due to particulate matter and other regulated pollutants. Climate change, through creating atmospheric conditions favoring ozone formation, has been and will continue to increase ozone concentrations in many parts of world. Worldwide, ozone is responsible for several hundreds of thousands of premature deaths and tens of millions of asthma-related emergency room visits annually. To combat ozone pollution globally, more aggressive reductions in fossil fuel consumption are needed to cut NO and VOCs as well as greenhouse gas emissions. Meanwhile, preventive and therapeutic strategies are needed to alleviate the detrimental effects of ozone especially in more susceptible individuals. Interventional trials in humans are needed to evaluate the efficacy of antioxidants and ozone-scavenging compounds that have shown promising results in animal studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.02518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834528PMC
October 2020

Characteristics of air pollutants inside and outside a primary school classroom in Beijing and respiratory health impact on children.

Environ Pollut 2019 Dec 30;255(Pt 1):113147. Epub 2019 Aug 30.

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan; Institute of Nature and Environmental Technology, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. Electronic address:

This study investigated the spatial and temporal distributions of particulate and gaseous air pollutants in a primary school in Beijing and assessed their health impact on the children. The results show that air quality inside the classroom was greatly affected by the input of outdoor pollutants; high levels of pollution were observed during both the heating and nonheating periods and indicate that indoor and outdoor air pollution posed a threat to the children's health. Traffic sources near the primary school were the main contributors to indoor and outdoor pollutants during both periods. Moreover, air quality in this primary school was affected by coal combustion and atmospheric reactions during the heating and nonheating periods, respectively. Based on the estimation by exposure-response functions and the weighting of indoor and outdoor pollutants during different periods, the levels of PM, PM and O at school had adverse respiratory health effects on children. Longer exposures during the nonheating period contributed to higher health risks. These results emphasized that emission sources nearby had a direct impact on air quality in school and children's respiratory health. Therefore, measures should be taken for double control on air pollution inside and outside the classroom to protect children from it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2019.113147DOI Listing
December 2019

PDK1 Regulates Transition Period of Apical Progenitors to Basal Progenitors by Controlling Asymmetric Cell Division.

Cereb Cortex 2020 01;30(1):406-420

Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing 210009, China.

The six-layered neocortex consists of diverse neuron subtypes. Deeper-layer neurons originate from apical progenitors (APs), while upper-layer neurons are mainly produced by basal progenitors (BPs), which are derivatives of APs. As development proceeds, an AP generates two daughter cells that comprise an AP and a deeper-layer neuron or a BP. How the transition of APs to BPs is spatiotemporally regulated is a fundamental question. Here, we report that conditional deletion of phoshpoinositide-dependent protein kinase 1 (PDK1) in mouse developing cortex achieved by crossing Emx1Cre line with Pdk1fl/fl leads to a delayed transition of APs to BPs and subsequently causes an increased output of deeper-layer neurons. We demonstrate that PDK1 is involved in the modulation of the aPKC-Par3 complex and further regulates the asymmetric cell division (ACD). We also find Hes1, a downstream effecter of Notch signal pathway is obviously upregulated. Knockdown of Hes1 or treatment with Notch signal inhibitor DAPT recovers the ACD defect in the Pdk1 cKO. Thus, we have identified a novel function of PDK1 in controlling the transition of APs to BPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhz146DOI Listing
January 2020

The methyl-triclosan induced caspase-dependent mitochondrial apoptosis in HepG2 cells mediated through oxidative stress.

Ecotoxicol Environ Saf 2019 Oct 1;182:109391. Epub 2019 Jul 1.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China. Electronic address:

Methyl-triclosan (MTCS) is a dominant transformation product of triclosan (TCS), which has been widely used as an effective antimicrobial ingredient with increasing concentrations in the environment. MTCS shows higher persistence in environment than its parent chemical TCS. The toxic effects of MTCS and toxicological mechanism are not well understood up to now. This study investigated the cytotoxic effects of MTCS in HepG2 cells in terms of cell viability, apoptosis induction, ROS production, GSH/GSSG levels, Mitochondrial Membrane Potential (MMP) reduction, LDH release, glucose uptake and ATP production. Moreover, the related gene transcripts were measured with RT-qPCR assay. Cytotoxic experiments in HepG2 cells revealed that MTCS exposure at micromol per liter levels had toxic effects as evidenced by decreased cell survival, elevated cell apoptosis, reduced MMP and increased LDH release. These toxic effects were associated with increased ROS production and reduced GSH/GSSG ratio. Meanwhile, elevated glucose uptake and ATP production indicated that MTCS induced membrane damages resulted not from a typical mitochondrial uncoupler, but from oxidative stress. Analysis of gene transcripts showed that MTCS exposure induced mRNA expressions alterations associated with oxidative stress response, energy production, cell cycle regulation and cell apoptosis. In general, the caspase-dependent mitochondrial apoptosis pathway might play a role in MTCS induced cytotoxicity in HepG2 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.109391DOI Listing
October 2019

Transcriptome analysis of response mechanism to ammonia stress in Asian clam (Corbicula fluminea).

Aquat Toxicol 2019 Sep 26;214:105235. Epub 2019 Jun 26.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Corbicula fluminea is highly sensitive to ammonia, and its response mechanism to ammonia stress is unclear. In this study, C. fluminea was exposed to different levels of ammonia (control group, 10 mg/L, and 25 mg/L) for 24 h and 48 h. A comparative analysis of transcriptome sequencing (RNA-seq) of C. fluminea digestive gland showed that the expression of 6742 genes (11.54%) was significantly affected by ammonia stress. The TLR, NF-κB, FOXO, and apoptotic signaling pathways were involved in the regulation. The differential expression of 14 genes was confirmed by real-time PCR. In summary, the response mechanism of C. fluminea digestive gland under ammonia stress may be different from that of oxidative stress in marine vertebrates. Also, the NMDAR-mediated pathway may not be the main mechanism in the response to ammonia stress in C. fluminea. The present study is a preliminary study for further investigation into ammonia toxicity in shellfish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2019.105235DOI Listing
September 2019

Health effects of air pollution: what we need to know and to do in the next decade.

J Thorac Dis 2019 Apr;11(4):1727-1730

Beijing Innovation Center for Engineering Science and Advanced Technology, College of Environmental Sciences and Engineering and Center for Environment and Health, Peking University, Beijing 100000, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2019.03.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531724PMC
April 2019

Genomic DNA methylation signatures in different tissues after ambient air particulate matter exposure.

Ecotoxicol Environ Saf 2019 Sep 28;179:175-181. Epub 2019 Apr 28.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

DNA methylation (5-mc) is one of the several epigenetic markers, and is generally associated with the inhibition of gene expression. Both hyper and hypo DNA methylation are associated with the diseases. Exposure to fine particles with a diameter of 2.5 μm or less (PM) is a pervasive risk factor for cardiopulmonary mortality, metabolic disorders, cognition damage, and etc.. Recent reports pointed toward that these diseases were associated with the altered DNA methylation level of some specific-gene, potentially suggesting that the DNA methylation alteration was involved in the health hazard derived from the PM exposure. In this study, we systematically investigated the global DNA methylation level of most tissues, including lung, heart, testis, thymus, spleen, epididymal fat, hippocampus, kidney, live, after short and long term PM exposure. After acute PM exposure, the global hypo-methylation in DNA was observed in lung and heart. Notably, after chronic PM exposure, level of global DNA methylation decreased in most organs which included lung, testis, thymus, spleen, epididymal fat, hippocampus and blood. The present study systematically demonstrated the global DNA methylation changes by PM exposure, and put forward a possible orientation for further exploring the effects of ambient air particles exposure on the specific organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.04.049DOI Listing
September 2019

The global DNA and RNA methylation and their reversal in lung under different concentration exposure of ambient air particulate matter in mice.

Ecotoxicol Environ Saf 2019 May 4;172:396-402. Epub 2019 Feb 4.

Laboratory of Environmental Criteria and Risk Assessment & Environmental Standards Institute, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Particulate matter (PM) in air pollution is a pervasive risk factor in pulmonary diseases that are always associated with gene expression level alterations in many specific-genes. DNA methylation (5-methylcytosine [5mC]) and RNA methylation (N6-methyladenine [6 mA]) influence the gene expression from transcription and post-transcription level, and the DNA hydroxymethylation (5-hydroxymethylcytosine [5hmC]) is the oxidized form of 5mC. In the present study, the levels of global 5mC, 5hmC and 6 mA of lungs in experimental mice were investigated. We divided the animals into 3 groups randomly, the group 1 was exposed to heavy PM for 24 h in the unfiltered chamber, the group 2 was exposed to filtered air in the filtered chamber, and the group 3 was 10 of the mice in the group 1 after 24 h exposure and then being moved to the filtered chamber for further 120 h exposure. The morphology of lungs showed that acute PM exposure impaired the structure of pulmonary alveolus. Meanwhile, the global level of DNA methylation was decreased, and DNA hydroxymethylation and RNA methylation levels were increased in lungs after PM exposure for only 24 h. Very notably, after being exposed in purified air for 120 h, the pulmonary morphology, the global levels of DNA methylation, DNA hydroxymethylation and RNA methylation of lungs were all reversed. The present study clearly demonstrated the alteration of DNA and RNA methylation after acute heavy PM exposure and emphasized the reversal of the symptoms caused by PM exposure after the air purification, which provided us a new idea for the intervention of the adverse health effects from air pollution. CAPSULE: Acute PM exposure resulted in reduced global DNA methylation and increased global DNA hydroxymethylcytosine and RNA methylation, and air purification reversed these alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.01.111DOI Listing
May 2019

Author Correction: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

Nature 2018 09;561(7723):E30

Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.

In this Letter, the graphs in Fig. 2a and c were inadvertently the same owing to a copy and paste error from the original graphs in Prism. The Source Data files containing the raw data were correct. Fig. 2c has been corrected online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-018-0270-4DOI Listing
September 2018

High-Throughput Screens To Identify Autophagy Inducers That Function by Disrupting Beclin 1/Bcl-2 Binding.

ACS Chem Biol 2018 08 21;13(8):2247-2260. Epub 2018 Jun 21.

Center for Autophagy Research, Department of Internal Medicine , University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United States.

Autophagy, a lysosomal degradation pathway, plays a crucial role in cellular homeostasis, development, immunity, tumor suppression, metabolism, prevention of neurodegeneration, and lifespan extension. Thus, pharmacological stimulation of autophagy may be an effective approach for preventing or treating certain human diseases and/or aging. We sought to establish a method for developing new chemical compounds that specifically induce autophagy. To do this, we developed two assays to identify compounds that target a key regulatory node of autophagy induction-specifically, the binding of Bcl-2 (a negative regulator of autophagy) to Beclin 1 (an allosteric modulator of the Beclin 1/VPS34 lipid kinase complex that functions in autophagy initiation). These assays use either a split-luciferase assay to measure Beclin 1/Bcl-2 binding in cells or an AlphaLISA assay to directly measure direct Beclin 1/Bcl-2 binding in vitro. We screened two different chemical compound libraries, comprising ∼300 K compounds, to identify small molecules that disrupt Beclin 1/Bcl-2 binding and induce autophagy. Three novel compounds were identified that directly inhibit Beclin 1/Bcl-2 interaction with an IC in the micromolar range and increase autophagic flux. These compounds do not demonstrate significant cytotoxicity, and they exert selectivity for disruption of Bcl-2 binding to the BH3 domain of Beclin 1 compared with the BH3 domain of the pro-apoptotic Bcl-2 family members, Bax and Bim. Thus, we have identified candidate molecules that serve as lead templates for developing potent and selective Beclin 1/Bcl-2 inhibitors that may be clinically useful as autophagy-inducing agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschembio.8b00421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250051PMC
August 2018
-->