Publications by authors named "Qianqian Xiao"

29 Publications

  • Page 1 of 1

Identification of miRNA-mRNA Pairs in the Alzheimer's Disease Expression Profile and Explore the Effect of miR-26a-5p/PTGS2 on Amyloid-β Induced Neurotoxicity in Alzheimer's Disease Cell Model.

Front Aging Neurosci 2022 15;14:909222. Epub 2022 Jun 15.

Department of Neurology, The Third Affiliated Hospital of Naval Medical University, Shanghai, China.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify the AD-specific differentially expressed miRNAs and mRNAs, we used bioinformatics analysis to study candidate miRNA-mRNA pairs involved in the pathogenesis of AD. These miRNA-mRNAs may serve as promising biomarkers for early diagnosis or targeted therapy of AD patients. In this study, based on the AD mRNA and miRNA expression profile data in Gene Expression Omnibus (GEO), through differential expression analysis, functional annotation and enrichment analysis, weighted gene co-expression network analysis, miRNA-mRNA regulatory network, protein-protein interaction network, receiver operator characteristic and Least absolute shrinkage and selection operator (LASSO) regression and other analysis, we screened the key miRNA-mRNA in the progress of AD: miR-26a-5p/PTGS2. Dual-luciferase and qPCR experiments confirmed that PTGS2 is a direct target gene of miR-26a-5p. The expression of miR-26a-5p in the peripheral blood of AD patients and AD model cells (SH-SY5Y cells treated with Aβ) was up-regulated, and the expression of PTGS2 was down-regulated. Functional gain -loss experiments confirmed that PTGS2 protects AD model cells from damage by inhibiting proliferation and migration. However, the expression of miR-26a-5p promotes the proliferation of AD model cells. It is further found that PTGS2 is involved in the regulation of miR-26a-5p and can reverse the effect of miR-26a-5p on the proliferation of AD model cells. In addition, through network pharmacology, qPCR and CCK-8, we found that baicalein may affect the progression of AD by regulating the expression of PTGS2. Therefore, PTGS2 can be used as a target for AD research, and miR-26a-5p/PTGS2 can be used as an axis of action to study the pathogenesis of AD.
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http://dx.doi.org/10.3389/fnagi.2022.909222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249435PMC
June 2022

Integrated proteomic analysis to explore the molecular regulation mechanism of IL-33 mRNA increased by black carbon in the human endothelial cell line EA.hy926.

Environ Toxicol 2022 Jul 1. Epub 2022 Jul 1.

Department of Toxicology, School of Public Health, Peking University, Beijing, People's Republic of China.

Black carbon (BC) correlates with the occurrence and progression of atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that BC could impair vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that IL-33 exerts a significant biological role in cardiovascular disease, but little is known about the molecular regulation of IL-33 expression at present. We first found that BC significantly increased IL-33 mRNA in EA.hy926 cells in a concentration and time-dependent manner, and we conducted this study to explore its underlying mechanism. We identified that BC induced mitochondrial damage and suppressed autophagy function in EA.hy926 cells, as evidenced by elevation of the aspartate aminotransferase (GOT2), reactive oxygen species (ROS) and p62, and the reduction of mitochondrial membrane potential (ΔΨm). However, ROS cannot induce IL-33 mRNA-production in BC-exposed EA.hy926 cells. Further, experiments revealed that BC could promote IL-33 mRNA production through the PI3K/Akt/AP-1 and p38/AP-1 signaling pathways. It is concluded that BC could induce oxidative stress and suppress autophagy function in endothelial cells. This study also provided evidence that the pro-cardiovascular-diseases properties of BC may be due to its ability to stimulate the PI3K/AKT/AP-1 and p38/AP-1 pathway, further activate IL-33 and ultimately result in a local vascular inflammation.
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http://dx.doi.org/10.1002/tox.23608DOI Listing
July 2022

Role of in Cardiovascular Disease.

J Pers Med 2022 Jun 20;12(6). Epub 2022 Jun 20.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Cholesterol homeostasis plays a significant role in cardiovascular disease. Previous studies have indicated that ATP-binding cassette transporter A1 () is one of the most important proteins that maintains cholesterol homeostasis. mediates nascent high-density lipoprotein biogenesis. Upon binding with apolipoprotein A-I, facilitates the efflux of excess intracellular cholesterol and phospholipids and controls the rate-limiting step of reverse cholesterol transport. In addition, ABCA1 interacts with the apolipoprotein receptor and suppresses inflammation through a series of signaling pathways. Thus, may prevent cardiovascular disease by inhibiting inflammation and maintaining lipid homeostasis. Several studies have indicated that post-transcriptional modifications play a critical role in the regulation of ABCA1 transportation and plasma membrane localization, which affects its biological function. Meanwhile, carriers of the loss-of-function gene are often accompanied by decreased expression of and an increased risk of cardiovascular diseases. We summarized the transcription regulation mechanism, mutations, post-translational modifications, and their roles in the development of dyslipidemia, atherosclerosis, ischemia/reperfusion, myocardial infarction, and coronary heart disease.
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http://dx.doi.org/10.3390/jpm12061010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225161PMC
June 2022

Epidemiological investigation and reinfection evaluation of Toxoplasma gondii in chickens in Shandong Province, China.

Exp Parasitol 2022 Jul 17;238:108276. Epub 2022 May 17.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. Electronic address:

Toxoplasma gondii infects almost all warm-blooded animals, and toxoplasmosis is a common zoonotic parasitic disease worldwide. A nested PCR with high specificity and sensitivity was developed in this study based on the data collected on the infection rate of toxoplasmosis in chickens in Shandong province, and the effect of low temperature on the infectivity of tachyzoites was investigated. The sampling data showed that the total prevalence of T. gondii in Shandong province was 12.3%, and the positive rate varied in different regions, ranging from 6.7% to 21%. Chickens were infected with T. gondii under laboratory conditions, and positive chicken hearts were stored under various cold conditions to infect mice for reinfection evaluation. The results demonstrated that the parasites maintained high infectivity in mice even after 6 h of storage at -20 °C ambient temperature, indicating that short-term cryopreservation is not effective in reducing the risk of T. gondii transmission. These results form the basis for assessing the risk of toxoplasmosis contamination in consumed chicken products and provide information on the prevention of parasite transmission from animals to humans.
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http://dx.doi.org/10.1016/j.exppara.2022.108276DOI Listing
July 2022

Exploration of potential mechanism of interleukin-33 up-regulation caused by 1,4-naphthoquinone black carbon in RAW264.7 cells.

Sci Total Environ 2022 Aug 19;835:155357. Epub 2022 Apr 19.

Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China. Electronic address:

Background: As air pollution has been paid more attention to by public in recent years, effects and mechanism in particulate matter-triggered health problems become a focus of research. Lysosomes and mitochondria play an important role in regulation of inflammation. Interleukin-33 (IL-33) has been proved to promote inflammation in our previous studies. In this research, macrophage cell line RAW264.7 was used to explore the potential mechanism of upregulation of IL-33 induced by 1,4-naphthoquinone black carbon (1,4-NQ-BC), and to explore changes of lysosomes and mitochondria during the process.

Results: 50 μg/mL 1,4-NQ-BC exposure for 24 h dramatically increased expression of IL-33 in RAW264.7 cells. Lysosomal membrane permeability was damaged by 1,4-NQ-BC treatment, and higher mitochondrial membrane potential and ROS level were induced by 1,4-NQ-BC. The results of proteomics suggested that expression of ferritin light chain was increased after cells were challenged with 1,4-NQ-BC, and it was verified by Western blot. Meanwhile, expressions of p62 and LC3B-II were increased by 50 μg/mL 1,4-NQ-BC in RAW264.7 cells. Ultimately, expression of IL-33 could return to same level as control in cells treated with 50 μg/mL 1,4-NQ-BC and 50 μM deferoxamine combined.

Conclusions: 1,4-NQ-BC induces IL-33 upregulation in RAW264.7 cells, and it is responsible for higher lysosomal membrane permeability and ROS level, lower mitochondrial membrane potential, and inhibition of autophagy. Ferritin light chain possibly plays an important role in the upregulation of IL-33 evoked by 1,4-NQ-BC.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155357DOI Listing
August 2022

Involvement of Urm1, a Ubiquitin-Like Protein, in the Regulation of Oxidative Stress Response of Toxoplasma gondii.

Microbiol Spectr 2022 04 24;10(2):e0239421. Epub 2022 Mar 24.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural Universitygrid.440622.6, Tai'an, China.

Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the ability to act as a posttranslational protein modifier. Here, we characterized the Toxoplasma gondii homolog of URM1 located in the tachyzoite cytoplasm. The total loss of the TgURM1 resulted in a significant reduction in parasite invasion, replication, and virulence in mice, revealing that TgURM1 plays a pivotal role in T. gondii survival. For TgURM1, urmylation was significantly induced by oxidative stress, and mutations of the C-terminal glycine-glycine motif of TgURM1 blocked the urmylation process. Furthermore, the TgURM1 knockout strain was intolerant to oxidative stress, suggesting that TgURM1 is involved in the oxidative stress process. TgAHP1, an alkyl hydroperoxide reductase, was screened via proximity-based protein labeling techniques and proteomics and was shown to interact with TgURM1 under oxidative stress conditions. In conclusion, TgURM1 is a UBL protein involved in the response of to oxidative stress. T. gondii has an intricate life cycle which involves multiple morphologically and physiologically distinct stages, and posttranslational modifications (PTMs) may be key regulators of protein expression at relevant life cycle stages. In recent years, ubiquitin-like proteins with modification functions have been discovered and studied, including Sumo, Rub1, ATG8, and ATG12. Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL), which is considered to be the oldest ubiquitin-like system. In this study, we identified the Urm1 gene in and explored that the urmylation of Urm1 was significantly induced by oxidative stress. Fewer studies have been conducted on ubiquitin-like proteins of parasites, and our results provide theoretical support for the research of metabolic regulation and antioxidative stress processes in T. gondii.
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http://dx.doi.org/10.1128/spectrum.02394-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045335PMC
April 2022

Effects of intrauterine and lactational exposure to lanthanum nitrate on BALB/c offspring mice: Developmental immunotoxicity and self-recovery.

Toxicol Lett 2022 Jun 25;362:17-25. Epub 2022 Jan 25.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Lanthanum, a major rare earth element, can exert detrimental effects on the adult immune system, but its developmental immunotoxicity (DIT) remains obscure. This study was designed to evaluate the DIT of lanthanum nitrate (LN) and the self-recovery of LN-induced DIT 21 days following cessation of exposure. BALB/c pregnant dams were exposed to 0, 0.1, 1, and 10 mg/kg body weight/day LN by gavage during gestation and lactation. Results showed that in male offspring, LN markedly inhibited the adaptive immunity at postanal day 21 (PND21) and the inhibitory effect on cellular immunity continued to PND42 (after three weeks of self-recovery). In female offspring, LN suppressed cellular immunity at both PND21 and PND42. Moreover, decreased relative organ weight of thymus, humoral immunity and proportion of double-positive T cells in thymus were also observed at PND42. Bcl-xl protein level decreased in thymus of female at PND42, while the level of β-catenin increased. These changes might contribute to accelerating the degeneration and weight loss of thymus. Overall, in-utero and postanal exposure to LN could induce impairments of immunity in offspring, especially the female, and adaptive immunosuppression would persist throughout development into adulthood. The LOAEL of LN for DIT should be 1 mg/kg.
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http://dx.doi.org/10.1016/j.toxlet.2022.01.013DOI Listing
June 2022

Pharmacokinetics, oral bioavailability and metabolic analysis of solasodine in mice by dried blood spot LC-MS/MS and UHPLC-Q-Exactive MS.

J Pharm Biomed Anal 2022 Feb 24;210:114542. Epub 2021 Dec 24.

School of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang, Shandong 261053, China. Electronic address:

Solasodine, a major ingredient in Solanaceae family, has various biological functions such as inducing neurogenesis, anticonvulsant and anti-tumor. Its risk assessment has also drawn public attention. However, little is known about its oral bioavailability and metabolic process. In this study, an liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of solasodine in mice dried blood spot (DBS) samples. To block nonspecific adsorption, DBS samples were pretreated with bovine serum albumin (BSA) and then extracted with ethyl acetate. This method was applied to a pharmacokinetic and bioavailability study of solasodine. The absolute bioavailability was only 1.28%. Thereafter, its metabolites in mice were characterized using an ultra-performance liquid chromatography Q-Exactive high-resolution mass spectrometer (UHPLC-QE-HRMS). Several isomeric metabolites were well separated and differentiated using their retention time, fragmentation pathways and correspondingly fragmentation rules of solasodine. As a result, 21 metabolites were characterized including 16 phase I and 5 phase II metabolites. The proposed metabolic pathways showed that solasodine mainly experienced oxidation, dehydration, dehydrogenation and sulfation. These results could help us to better understand the efficacy and safety of solasodine.
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http://dx.doi.org/10.1016/j.jpba.2021.114542DOI Listing
February 2022

Chlorocholine chloride induced testosterone secretion inhibition mediated by endoplasmic reticulum stress in primary rat Leydig cells.

Toxicol Lett 2022 Mar 25;356:161-171. Epub 2021 Dec 25.

Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Chlorocholine chloride (CCC) is well acknowledged as a plant growth regulator and may be considered as a potential environmental endocrine disrupting chemical. In our previous studies, it was found that CCC exposure at a pubertal stage reduced the serum and testicular levels of testosterone, decreased the sperm motility and delayed the puberty onset. However, the molecular mechanisms of CCC-induced testosterone secretion disorders remain unclear. In this study, we found that CCC exposure above 20 μg/mL inhibited the secretion of testosterone in Sprague-Dawley rats Leydig cells. Proteomic and pathway enrichment analysis indicated that CCC might induce endoplasmic reticulum (ER) stress. Western blot detection showed CCC exposure at 100, 200 μg/mL increased the protein level of glucose-regulated protein 78 (GPR78), C/EBP-homologous protein (CHOP), the ubiquitin-conjugating enzyme E2 D1 (UBE2D1) and the ring finger protein (RNF185) in the Leydig cells. The Leydig cells treated with 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, rescued the testosterone secretion disorders and alleviated CCC-induced increase in the ER stress related protein levels at 200 μg/mL CCC treatment. Overall, CCC in vitro exposure might disturb testosterone production of Leydig cells and endoplasmic reticulum stress was involved in it.
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http://dx.doi.org/10.1016/j.toxlet.2021.12.018DOI Listing
March 2022

Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in .

Oxid Med Cell Longev 2021 21;2021:1675652. Epub 2021 Sep 21.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

is a protozoan parasite that is widely parasitic in the nucleated cells of warm-blooded animals. Bioinformatic analysis of alkyl hydroperoxide reductase 1 (AHP1) of is a member of the Prxs family and exhibits peroxidase activity. Cys was certified to be a key enzyme active site of TgAHP1, indicating that the enzyme follows a cysteine-dependent redox process. TgAHP1 was present in a punctate staining pattern anterior to the nucleus. Oxidative stress experiments showed that the ∆Ahp1 strain was more sensitive to tert-butyl hydroperoxide (tBOOH) than hydrogen peroxide (HO), indicating that tBOOH may be a sensitive substrate for TgAHP1. Under tBOOH culture conditions, the ∆Ahp1 strain was significantly less invasive, proliferative, and pathogenic in mice. This was mainly due to the induction of tBOOH, which increased the level of reactive oxygen species in the parasites and eventually led to apoptosis. This study shows that TgAHP1 is a peroxisomes protein with cysteine-dependent peroxidase activity and sensitive to tBOOH.
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http://dx.doi.org/10.1155/2021/1675652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481037PMC
January 2022

Effects of 4-nonylphenol on adipogenesis in 3T3-L1 preadipocytes and C3H/10T1/2 mesenchymal stem cells.

J Appl Toxicol 2022 04 22;42(4):588-599. Epub 2021 Sep 22.

Department of Toxicology, School of Public Health, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, Beijing, China.

Obesogens are a subset of endocrine disruptor chemicals (EDCs) that cause obesity. The typical EDC 4-nonylphenol (4-NP) has been identified as an obesogen. However, the in vitro effects of 4-NP on adipogenesis remain unclear. In this study, 3T3-L1 preadipocytes and C3H/10T1/2 mesenchymal stem cells (MSCs) were used to investigate the influence of 4-NP on adipogenesis. The differentiation protocols for 3T3-L1 preadipocytes and C3H/10T1/2 MSCs took 8 and 12 days, respectively, beginning at Day 0. In differentiated 3T3-L1 preadipocytes, 20 μM 4-NP decreased cell viability on Days 4 and 8. Exposure to 4-NP inhibited triglyceride (TG) accumulation and adipogenic marker expression on Days 0-8, but the inhibitory effects were weaker on Days 2-8. The protein expression of pSTAT3 or STAT3 decreased on Days 0-8 and 2-8. Conversely, 4-NP promoted TG accumulation and the adipogenic marker expression in C3H/10T1/2 adipocytes. The opposing effects were attributed to physiological differences between the two cell lines. The 3T3-L1 preadipocytes are dependent on mitotic clonal expansion (MCE) to drive differentiation, while C3H/10T1/2MSCs and human preadipocytes are not. Additionally, 4-NP downregulated β-catenin expression in C3H/10T1/2 adipocytes. Accordingly, we hypothesized that 4-NP promotes adipogenesis. The role of the canonical Wnt pathway in the promotion of adipogenesis by 4-NP requires further validation. This study provides new insights into the mechanisms and appropriate risk management of 4-NP.
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http://dx.doi.org/10.1002/jat.4241DOI Listing
April 2022

Effects of prenatal chlorocholine chloride exposure on pubertal development and reproduction of male offspring in rats.

Toxicol Lett 2021 Oct 16;351:28-36. Epub 2021 Aug 16.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Chlorocholine chloride (CCC) promote plant growth as a regulator. Emerging evidence by our group showed that CCC might restrain the puberty onset and impair the reproductive functions in male rats through HPT axis. In this study, we further investigated the effects of prenatal CCC exposure on pubertal development, reproduction of male offspring in rats and explored the underlying mechanisms. The results showed that CCC of 137.5 and 200 mg/kg bw/day delayed the age of preputial separation (PPS), decreased the sperm motility of male offspring. PP1γ2 which is an essential protein in spermatogenesis reduced in 137.5 and 200 mg/kg bw/day groups. Crucial hormones involved in hypothalamic-puititary-testicular (HPT) axis decreased at postnatal day (PND) 30. It was indicated that CCC exposure in pregnancy might disturb the pubertal development, reproductive functions of male offspring through HPT axis and disturb the sperm motility through PP1γ2.
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http://dx.doi.org/10.1016/j.toxlet.2021.08.005DOI Listing
October 2021

Adaptation of AMPK-mTOR-signal pathways and lipid metabolism in response to low- and high-level rapeseed meal diet in Chinese perch (Siniperca chuatsi).

J Comp Physiol B 2021 09 9;191(5):881-894. Epub 2021 Aug 9.

College of Fisheries, Chinese Perch Research Center, Huazhong Agricultural University, Wuhan, 430070, China.

It is well known that carnivorous fish cannot use plant-proteins efficiently. They affect lipid metabolism of fish and cause serious problems to fish health. The reasons for this deficiency of fish metabolism are not known well. Chinese perch, a carnivorous fish, can accept artificial diet after domestication and is also considered as a novel model of fish for nutrition studies. Therefore, the aim of this study was to explore the effect of fish meal replacement by low- or high-rapeseed meal on lipid and glucose metabolism of Chinese perch. Three experimental diets were formulated with 0, 10%, and 30% rapeseed meal, named as Control, RSL, and RSH groups, respectively. After 8-weeks of the feeding trial, the inhibition of growth and fat deposition were observed in Chinese perch fed with rapeseed meal diets compared to the control group. Fish fed with RSL diets showed decreased food intake, serum low density lipoprotein (LDL), phosphorylated Grb10 (P < 0.05), inhibited fatty acid (FA) transport (lipoprotein lipase (LPL)), and glycerol synthesis (phosphoenol pyruvate carboxykinase (PEPCK)) in the liver. In addition, fish fed with RSL diets were also inhibited FA synthesis (fatty acid synthase (FAS), sterol regulatory element binding protein 1 (SREBP1), and Acetyl-CoA carboxylase (ACC1)), lipid uptake (hepatic lipase (HL)), β-oxidation (carnitine palmitoyltransferase I (CPT1)), and glycerol synthesis (PEPCK) in the visceral adipose tissue. Fish fed with RSH diets showed phosphorylated AMPK, inhibited FA synthesis (SREBP1, ACC1, and FAS), while enhanced lipolysis (hormone-sensitive lipase (HSL)), and then reduced Acetyl-CoA pool. In turn, β-oxidation (peroxisome proliferator-activated receptor-a (PPARα) and CPT1) was inhibited, while glycolysis (glucose-6-phosphatase (G6PD) and pyruvate carboxylase (PC)) were enhanced, consequently the lipid accumulation was decreased in the liver. Fish were also inhibited lipid uptake (LPL), that caused inhibiting of FA synthesis (SREBP1), β-oxidation (CPT1), glycerol synthesis (PEPCK), and in turn improved lipolysis (HSL) in the visceral adipose tissue. Our study suggested that both RSL and RSH diets decreased lipid accumulation in Chinese perch; however, the mechanism of lipid metabolism was different. Fish accepted less diet in RSL group, which inhibited lipid metabolism in the liver and in the visceral adipose tissues, while fish in RSH group activated AMPK pathway, inhibited FA synthesis, and enhanced lipolysis, which reduced Acetyl-CoA pool in the liver. Subsequently, lipid uptake and metabolism were inhibited in the visceral adipose tissue of RSH fish.
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http://dx.doi.org/10.1007/s00360-021-01393-7DOI Listing
September 2021

BC and 1,4NQ-BC up-regulate the cytokines and enhance IL-33 expression in LPS pretreatment of human bronchial epithelial cells.

Environ Pollut 2021 Jan 14;273:116452. Epub 2021 Jan 14.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Black carbon (BC) reacts with different substances to form secondary pollutants called aged black carbon, which causes inflammation and lung damage. BC and aged BC may enhance IL-33 in vivo, which may be derived from macrophages. The pro-inflammatory effect of IL-33 makes it essential to determine the source of IL-33, so it guides us to explore how to alleviate lung injury. In this study, a human bronchial epithelial cell line of 16HBE cells was selected, and aged BC (1,4-NQ coated BC and ozone oxidized BC) was used. We found that both BC and aged BC were able to up-regulate the mRNA expression of IL-1β, IL-6, and IL-8 except IL-33. However, the Mitogen-activated protein kinases (MAPKs) and Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKTs) pathways remained inactive. After pretreatment with Lipopolysaccharide (LPS), IL-33 mRNA expression was significantly increased in 16HBE cells and MAPKs and PI3K/AKT were activated. These results suggested that MAPKs and PI3K/AKT pathways were involved in the elevation of IL-33. Furthermore, epithelial cells are unlikely to be the source of lung inflammation caused by elevated IL-33 in BC and aged BC.
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http://dx.doi.org/10.1016/j.envpol.2021.116452DOI Listing
January 2021

Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats.

J Neuropathol Exp Neurol 2020 12;79(12):1344-1353

From the Department of Toxicology, School of Public Health, Peking University.

Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.
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http://dx.doi.org/10.1093/jnen/nlaa143DOI Listing
December 2020

Maternal chlormequat chloride exposure disrupts embryonic growth and produces postnatal adverse effects.

Toxicology 2020 09 2;442:152534. Epub 2020 Jul 2.

Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

We showed previously that chlormequat chloride, a widely used plant growth regulator, could affect embryonic growth and growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis of rats. However, the potential effects of low dose chlormequat chloride exposure during pregnancy on embryonic and postnatal growth and development remain unclear. To further assess the risk of chlormequat chloride to human embryonic growth and postnatal health, we exposed maternal rats orally to the chemical during pregnancy at 5 mg/kg bw, a dose corresponding to the human acceptable daily intake (ADI) level set by World Health Organization (WHO), and determined the effects of chlormequat on embryo growth and postnatal health. We found that chlormequat chloride increased embryonic growth parameters, GH, and GH-releasing hormone (GHRH) levels, but did not affect somatostatin and IGF-1 on gestational day (GD) 11. In the pups of postnatal day (PD) 7, we observed increased head length, decreased body fat percentage, hypoglycemia, hyperlipidemia and hyperproteinemia. In conclusion, maternal exposure to chlormequat chloride during pregnancy disrupts the embryonic growth probably through its effects on growth regulators and even has adverse effects on postnatal health.
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http://dx.doi.org/10.1016/j.tox.2020.152534DOI Listing
September 2020

1,4NQ-BC enhances the lung inflammation by mediating the secretion of IL-33 which derived from macrophages.

Environ Pollut 2020 Oct 11;265(Pt A):114729. Epub 2020 Jun 11.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Black carbon (BC) is a product of incomplete combustion of fossil fuels and vegetation. The compelling evidence has demonstrated that it has a close relationship with several respiratory and cardiovascular diseases. BC provides the reactive sites and surfaces to absorb various chemicals, such as polycyclic aromatic hydrocarbons (PAH). Naphthoquinone is a typical PAHs which was found in particulate matter (PM) and 1,4NQ-BC owned high oxidative potential and cytotoxicity. IL-33 is an alarmin which increases innate immunity through Th2 responses. It was reported that IL-33 was a potent inducer of pro-inflammatory cytokines, like IL-6. In our previous study, it was revealed that 1,4NQ-BC instilled intratracheally to mice could trigger the lung inflammation and stimulate the secretion of IL-33 in lung tissue. We found that IL-33 could induce inflammation in lung itself. When the macrophages were eliminated, the secretion of IL-33 was reduced and the pathological damage in the lung was relieved after exposure to 1,4NQ-BC. Both MAPK and PI3K/AKT signal pathways were involved in the process of IL-33 secretion and the lung inflammation induced by 1,4NQ-BC. The findings herein support the notion that after exposure to 1,4NQ-BC, the increased secretion of IL-33 was mainly derived from macrophages through both MAPK and PI3K/AKT signal pathways.
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http://dx.doi.org/10.1016/j.envpol.2020.114729DOI Listing
October 2020

Bovine Lactoferrin Quantification in Dairy Products by a Simple Immunoaffinity Magnetic Purification Method Coupled with High-Performance Liquid Chromatography with Fluorescence Detection.

J Agric Food Chem 2020 Jan 10;68(3):892-898. Epub 2020 Jan 10.

School of Pharmacy , Weifang Medical University , 7166 Baotong West Street , Weifang , Shandong 261053 , China.

This study described a simple, specific, and sensitive method using immunoaffinity magnetic purification coupled with high-performance liquid chromatography-fluorescence (HPLC-FL) detection for determination of bovine lactoferrin (bLf) in dairy products. BLf was selectively extracted from dairy products using immunoaffinity beads and then detected by HPLC-FL with its intrinsic fluorescence. During the analysis, standard solutions of bLf were pretreated with Tween 20, an anti-adsorptive agent, for blocking the nonspecific binding of bLf to polypropylene tubes. The calibration curve was linear over the range of 0.8-30 μg mL. The validated method was successfully applied to measure bLf at the intact level in dairy products.
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http://dx.doi.org/10.1021/acs.jafc.9b06043DOI Listing
January 2020

Effect of long-chain saturated and unsaturated fatty acids on hypothalamic fatty acid sensing in Chinese perch (Siniperca chuatsi).

Comp Biochem Physiol B Biochem Mol Biol 2020 Mar 27;241:110395. Epub 2019 Dec 27.

College of Fisheries, Chinese Perch Research Center, Huazhong Agricultural University, Wuhan 430070, China; Innovation Base for Chinese Perch Breeding, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, China.

In order to evaluate fatty acid (FA) sensing systems based on binding to FAT/CD36 in hypothalamus of Chinese perch (Siniperca chuatsi) and its sensitivity to FAs with the same chain length and different unsaturation levels. The effects of Stearate (SA; C18:0), oleate (OA; C18:1 n-9), linoleic acid (LA; C18:2 n-6), and α-linolenic acid (ALA; C18:3 n-3) on hypothalamic FA sensing were evaluated by intracerebroventricular (ICV) administration. Food intake was assessed after 2, 4, 6, 8 and 12 h. Gene expression associated with FA sensing mechanism such as cd36, pparα and srebp1c, and neuropeptides controlling appetite such as pomca, cart, agrp2 and npy were assessed after 6 h. The ICV treatment of OA, LA and ALA activated FAT/CD36 and PPARα, rather than SA, and modulated gene expression levels of hypothalamic neuropeptides associated with appetite. And then, OA, LA and ALA inhibited food intake, which was consistent with the activation of hypothalamus FA sensing. Our data indicated some mechanisms of the hypothalamic FA sensing systems also existed in Chinese perch. It's worth noting that polyunsaturated fatty acids (PUFA) could also activate hypothalamic FA sensing mechanisms in Chinese perch. The unsaturation of FA appears to be extremely important for FA sensing mechanisms, since no major influences in Chinese perch after SA treatment. Our findings will contribute to the study of long-chain FAs sensing mechanisms in fish hypothalamus and highlight the importance of PUFAs in fish species.
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http://dx.doi.org/10.1016/j.cbpb.2019.110395DOI Listing
March 2020

A Study on The Driving Factors and Spatial Spillover of Carbon Emission Intensity in The Yangtze River Economic Belt under Double Control Action.

Int J Environ Res Public Health 2019 11 13;16(22). Epub 2019 Nov 13.

China-UK Low Carbon College, Shanghai Jiao Tong University, Shanghai 201306, China.

It is greatly important to promote low-carbon green transformations in China, for implementing the emission reduction commitments and global climate governance. However, understanding the spatial spillover effects of carbon emissions will help the government achieve this goal. This paper selects the carbon-emission intensity panel data of 11 provinces in the Yangtze River Economic Belt from 2004 to 2016. Then, this paper uses the Global Moran's I to explore the spatial distribution characteristics and spatial correlation of carbon emission intensity. Furthermore, this paper constructs a spatial econometric model to empirically test the driving path and spillover effects of relevant factors. The results show that there is a significant positive correlation with the provincial carbon intensity in the Yangtze River Economic Belt, but this trend is weakening. The provinces of Jiangsu, Zhejiang, and Shanghai are High-High agglomerations, while the provinces of Yunnan and Guizhou are Low-Low agglomerations. Economic development, technological innovation, and foreign direct investion (FDI) have positive effects on the reduction of carbon emissions, while industrialization has a negative effect on it. There is also a significant positive spatial spillover effect of the industrialization level and technological innovation level. The spatial spillover effects of FDI and economic development on carbon emission intensity fail to pass a significance test. Therefore, it is necessary to promote cross-regional low-carbon development, accelerate the R&D of energy-saving and emission-reduction technologies, actively enhance the transformation and upgrade industrial structures, and optimize the opening up of the region and the patterns of industrial transfer.
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http://dx.doi.org/10.3390/ijerph16224452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888273PMC
November 2019

The Inducible CYP4C71 Can Metabolize Imidacloprid in Laodelphax striatellus (Hemiptera: Delphacidae).

J Econ Entomol 2020 02;113(1):399-406

Department of Entomology, College of Plant Protection/The Key Laboratory of Monitoring and Management of Plant Diseases and Insects, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Laodelphax striatellus (Fallén) is an important rice pest species which has developed high resistance to imidacloprid. Previous studies have demonstrated that CYP6AY3v2 and CYP353D1v2 were constitutively overexpressed in a imidacloprid resistant strain and can metabolize imidacloprid to mediated metabolic resistance. Further studies still needed to explore whether there are other L. striatellus P450 enzymes that can also metabolize imidacloprid. In this study, the expression level of L. striatellus CYP4C71 was significantly upregulated both in laboratory strains and field strains of L. striatellus after imidacloprid treatment for 4 h. The capability of CYP4C71 to metabolize imidacloprid was investigated. The full-length CYP4C71 was cloned, and its open reading frame was 1,515 bp with an enzyme estimated to be 505 amino acid residues in size. Furthermore, CYP4C71 was heterologously expressed along with L. striatellus cytochrome P450 reductase (CPR) in insect cells. A carbon monoxide difference spectra analysis confirmed the successful expression of CYP4C71. The recombinant CYP4C71 showed high P450 O-demethylation activity with PNP as a substrate. In vitro metabolism studies showed that recombinant CYP4C71 can metabolize imidacloprid to an easily excreted hydroxy-form. The rate of imidacloprid depletion in response to imidacloprid concentration revealed Michaelis Menten kinetics (R2 fitted curve = 0.99) with a relative low affinity: Kcat = 0.032 ± 0.009 pmol depleted imidacloprid/min/pmol P450 and Km=85.19 ± 2.93 μM. A relative big Km (85.19 ± 2.93 μM) indicated relative low imidacloprid's affinity for the CYP4C71 enzyme. In conclusion, CYP4C71 was another P450 enzyme that can metabolize imidacloprid with a relatively low affinity.
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http://dx.doi.org/10.1093/jee/toz292DOI Listing
February 2020

Chlormequat chloride promotes rat embryonic growth and GH-IGF-1 axis.

Toxicology 2020 01 5;429:152326. Epub 2019 Nov 5.

Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Chlormequat chloride, a plant growth regulator, is widely applied in agriculture because it can promote sturdier growth of the crops. In this research, we found that rat embryo growth on GD11 was inhibited in vitro at 50 μg/ml but promoted in vivo at 75 mg/kg.bw by maternal oral exposure. Therefore, the concentrations of chlormequat chloride in the sera of the pregnant rats on gestation day (GD)11 were determined by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) test to be 1.94 ± 0.023 μg/ml, 3.84 ± 0.080 μg/ml, and 7.08 ± 0.11 μg/ml, respectively, when the pregnant rats were orally exposed to chlormequat chloride at 75, 137.5, and 200 mg/kg.bw. Hence, we performed WEC tests again and confirmed that the rat embryo growth in vitro was promoted by chlormequat chloride at 5 μg/mL. The embryonic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were increased by chlormequat chloride both in vitro and in vivo compared with the control ones. We concluded that chlormequat chloride could elevate GH and IGF-1 levels in embryos and promote embryonic growth both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.tox.2019.152326DOI Listing
January 2020

Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes.

Int Immunopharmacol 2019 Oct 17;75:105760. Epub 2019 Jul 17.

Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address:

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/β-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.
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http://dx.doi.org/10.1016/j.intimp.2019.105760DOI Listing
October 2019

Protective Role of Rabbit Nucleotide-Binding Oligomerization Domain-2 (NOD2)-Mediated Signaling Pathway in Resistance to Enterohemorrhagic Infection.

Front Cell Infect Microbiol 2018 26;8:220. Epub 2018 Jun 26.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

Nucleotide-binding oligomerization domain 2 (NOD2), a member of the NOD-like receptors (NLRs) family that is well-known to play a key role in innate immune responses and is involved in innate antibacterial responses. In this study, rabbit NOD2 (rNOD2) was cloned from rabbit kidney (RK) cells. It was distributed in various tissues, and the highest level of was detected in spleen. Moreover, the expression of was significantly upregulated in the heart, liver, and spleen induced by enterohemorrhagic (EHEC). Overexpression of rNOD2 induced the expression of pro-inflammatory cytokine, including β, γ, and , as well as defensins, including , and through the nuclear factor (NF)-κB signaling pathway. Furthermore, overexpression of rNOD2 inhibited the growth of EHEC, and knockdown of rNOD2 or inhibition of the NF-κB pathway promoted its replication. In addition, our results suggest that rNOD2 can significantly activate NF-κB signaling and trigger antibacterial defenses to increase the expression of pro-inflammatory cytokine and defensins after stimulation by EHEC. These findings are useful to further understanding the innate immune system of rabbits and providing a new perspective for the prevention of bacterial diseases in rabbits.
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http://dx.doi.org/10.3389/fcimb.2018.00220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031198PMC
July 2019

S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells.

Oncotarget 2016 Jun;7(25):38133-38142

Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.

YAP is an oncogenic transcriptional co-activator and is inhibited by the Hippo pathway. Recent studies have revealed that YAP is also a sensor of cell morphology and cell density and can be phosphorylated by cytoskeleton reorganization. Our previous study demonstrated that S100A7 was upregulated in several squamous cell carcinoma (SCC) specimens and was dramatically induced in SCC cells by suspension and dense culture as well as in xenografts. However, little is known about how S100A7 induction occurs in cancer cells. Here, we identify that S100A7 induction is accompanied by YAP phosphorylation in both suspended and dense A431 cells. This correlation reverses after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is repressed by nuclear YAP, which is further validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Strikingly, disruption of the F-actin promotes S100A7 expression via YAP by activation of the Hippo pathway. Furthermore, we demonstrate that repression of S100A7 by YAP required TEAD1 transcriptional factor. Taken together, our findings demonstrate for the first time that S100A7 is repressed by YAP via the Hippo pathway.
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http://dx.doi.org/10.18632/oncotarget.9477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122377PMC
June 2016

Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.

Oncotarget 2016 Feb;7(8):9513-24

Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.

Our previous study revealed that knockdown of CABYR-a/b increases the chemosensitivity of lung cancer cells through inactivation of Akt. Here, we demonstrated that depletion of CABYR-a/b significantly increased DR5 expression and sensitized lung cancer cells to TRAIL-induced apoptosis in vitro and/or in vivo. Importantly, treatment with AD5-10, a DR5-specific agonistic monoclonal antibody, was able to mimic TRAIL-induced apoptosis in CABYR-a/b-silenced cells. Strikingly, we identified that depletion of CABYR-a/b not only increased the expressions of p73 and DR5 but also decreased the phosphorylation of YAP S127. Loss- or gain-of-function studies of YAP and p73 revealed that double deletions of YAP and p73 effectively decreased the expression of DR5 and abolished TRAIL-induced apoptosis in CABYR-a/b knockdown cells. Conversely, the co-overexpression of YAP and p73 promoted the expression of DR5 and sensitized cells to TRAIL-induced apoptosis. Taken together, our results demonstrate that depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.
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http://dx.doi.org/10.18632/oncotarget.7069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891056PMC
February 2016

The Characteristics and Function of S100A7 Induction in Squamous Cell Carcinoma: Heterogeneity, Promotion of Cell Proliferation and Suppression of Differentiation.

PLoS One 2015 8;10(6):e0128887. Epub 2015 Jun 8.

Key laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, Beijing, China.

S100A7 is highly expressed in squamous cell carcinomas (SCC) and is related to the terminal differentiation of keratinocytes. However, its characteristic and function in SCC is not very known. In this present study, we used immunohistochemistry to examine the expression of S100A7 in 452 SCC specimens, including the lung, esophagus, oral cavity, skin, cervix, bladder, and three SCC cell lines. We found that S100A7-positive staining showed significant heterogeneity in six types of SCC specimen and three SCC cell lines. Further examination found that S100A7-positive cells and its expression at mRNA and protein levels could be induced in HCC94, FaDu, and A-431 cells both in vitro and in vivo using immunohistochemistry, real-time PCR, and Western blotting. Notably, the upregulation of squamous differentiation markers, including keratin-4, keratin-13, TG-1, and involucrin, also accompanied S100A7 induction, and a similar staining pattern of S100A7 and keratin-13 was found in HCC94 cells both in vitro and in vivo. Further study revealed that the overexpression of S100A7 significantly increased proliferation and inhibited squamous differentiation in A-431 cells both in vitro and in vivo. Conversely, silencing S100A7 inhibited cell growth and survival and increased the expression of keratin-4, keratin-13, TG-1, and involucrin in HCC94 cells. Therefore, these results demonstrate that S100A7 displays heterogeneous and inducible characteristic in SCC and also provide novel evidence that S100A7 acts as a dual regulator in promoting proliferation and suppressing squamous differentiation of SCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128887PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460013PMC
February 2016

Knockdown of CABYR-a/b increases chemosensitivity of human non-small cell lung cancer cells through inactivation of Akt.

Mol Cancer Res 2014 Mar 20;12(3):335-47. Epub 2013 Dec 20.

Key Laboratory of Cell Proliferation and Regulation of the Ministry of Education, Beijing Normal University, 19th Xinjiekouwai St. 100875, Beijing, China.

Unlabelled: CABYR is a calcium-binding tyrosine phosphorylation-regulated protein that was identified as a novel cancer testis antigen in lung cancer in our previous study. However, the role of CABYR as a driver of disease progression or as a chemosensitizer is poorly understood. This study sought to investigate the relationship between the expression levels of CABYR-a/b, which are the two predominant isoforms of the five isoform proteins encoded by CABYR, and chemosensitivity in non-small cell lung cancer cells. We found that the short hairpin RNA-mediated knockdown of CABYR-a/b significantly inhibited the proliferation of NCI-H460 and A549 cells and resulted in the attenuation of Akt phosphorylation, which is constitutively active in lung cancer cells. The silencing of CABYR-a/b expression notably impacted the downstream components of the Akt pathways: decreasing the phospho-GSK-3β (Ser9) levels and increasing the expression of the p53 and p27 proteins. Furthermore, CABYR-a/b knockdown led to a significant increase in chemosensitivity in response to chemotherapeutic drugs and drug-induced apoptosis, both in vitro and in vivo. Conversely, the transient transfection of CABYR-a/b-depleted cells with constitutively active Akt partially restored the resistance to cisplatin and paclitaxel and significantly decreased the activation of GSK-3β and cleaved PARP. Taken together, our results suggest that the inhibition of CABYR-a/b is a novel method to improve the apoptotic response and chemosensitivity in lung cancer and that this cancer testis antigen is an attractive target for lung cancer drug development.

Implications: Suppression of CABYR-a/b expression increases chemosensitivity of lung cancer cells by inhibiting Akt activity.
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http://dx.doi.org/10.1158/1541-7786.MCR-13-0391DOI Listing
March 2014

Multifunctional core-shell upconversion nanoparticles for targeted tumor cells induced by near-infrared light.

J Mater Chem B 2013 Jun 26;1(21):2757-2763. Epub 2013 Apr 26.

College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.

Here we synthesize silica-coated NaYF:Yb/Er nanocomposites with a photosensitizer hypericin covalently bound to silica shells ([email protected]@hypericin) successfully, exhibiting precise size-control, good water dispersity and excellent biocompatibility. Under near-infrared light (NIR) irradiation, UCNPs convert NIR light to strong green light which agrees well with the absorbance peak of the photosensitizer hypericin, and triggers hypericin to generate singlet oxygen effectively. The cell apoptosis studies by flow cytometry, fluorescence microscope imaging with Annexin V-FITC/PI and caspase-3 western blotting demonstrate that [email protected]@hypericin-FA displays outstanding performance in the induction of apoptosis of Hela cells and HepG2 cells under NIR light irradiation for a short time. At the same time, [email protected]@hypericin-FA nanocomposites are proved to exhibit little cytotoxicity by cell viability experiments. By the use of confocal microscopy, cell uptake results show that folate receptor FR(+) cell lines such as Hela cells could internalize more [email protected]@hypericin-FA than FR(-) cell lines, such as 293T cells, with highly selective cellular uptake. All the results indicate that [email protected]@hypericin-FA nanocomposites have a promising potential in the application of PDT and other diseases in deep tissues.
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http://dx.doi.org/10.1039/c3tb00575eDOI Listing
June 2013
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