Publications by authors named "Jiaqiang Pan"

37 Publications

Metabolomics analysis reveals the effects of copper on mitochondria-mediated apoptosis in kidney of broiler chicken (Gallus gallus).

J Inorg Biochem 2021 Nov 17;224:111581. Epub 2021 Aug 17.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu) is one of the ubiquitous environmental pollutants which have raised wide concerns about the potential toxic effects and public health threat. For deeply investigating the nephrotoxicity induced by Cu, the effects of Cu on mitochondria-mediated apoptosis in kidney were first to analyze by combining metabolomics and molecular biology techniques. In this study, broiler chicks were fed with different contents of Cu (11, 110, 220, and 330 mg/kg Cu) for 49 d. The results of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and transmission electron microscope showed that Cu could induce apoptosis in kidney, characterized by the increasing of TUNEL-positive cells and mitochondrial vacuolation. Additionally, a total of 62 differential metabolites were detected by liquid chromatography-mass spectrometry (LC-MS), and mainly enriched in the metabolic pathways including riboflavin metabolism, glutathione metabolism, sphingolipid metabolism, and glycerophospholipid metabolism, which were closely to mitochondrial metabolism. Meanwhile, the decreased mitochondrial membrane potential (MMP), increased mitochondrial membrane permeability and the change of mRNA and protein expression levels associated with mitochondria-mediated apoptosis and mitochondrial dynamics confirmed that Cu could induce mitochondria-mediated apoptosis. Therefore, our results demonstrated that Cu induced mitochondria-mediated apoptosis in kidney. Moreover, this study highlighted the metabolic characteristics of Cu to kidney, which suggested that mitochondrial metabolism could be considered as an important factor influencing toxicity.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111581DOI Listing
November 2021

Mitochondrial miR-1285 regulates copper-induced mitochondrial dysfunction and mitophagy by impairing IDH2 in pig jejunal epithelial cells.

J Hazard Mater 2021 Aug 12;422:126899. Epub 2021 Aug 12.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), a hazardous heavy metal, can lead to toxic effects on host physiology. Recently, specific mitochondria-localized miRNAs (mitomiRs) were shown to modulate mitochondrial function, but the underlying mechanisms remain undefined. Here, we identified mitomiR-1285 as an important molecule regulating mitochondrial dysfunction and mitophagy in jejunal epithelial cells under Cu exposure. Mitochondrial dysfunction and mitophagy were the important mechanisms of Cu-induced pathological damage in jejunal epithelial cells, which were accompanied by significant increase of mitomiR-1285 in vivo and in vitro. Knockdown of mitomiR-1285 significantly attenuated Cu-induced mitochondrial respiratory dysfunction, ATP deficiency, mitochondrial membrane potential reduction, mitochondrial reactive oxygen species accumulation, and mitophagy. Subsequently, bioinformatics analysis and luciferase reporter assay demonstrated that IDH2 was a direct target of mitomiR-1285. RNA interference of IDH2 dramatically reversed the effect that mitomiR-1285 knockdown relieved mitochondrial dysfunction and mitophagy induced by Cu, and the opposite effect was shown by overexpression of IDH2. Therefore, our results suggested that mitomiR-1285 aggravated Cu-induced mitochondrial dysfunction and mitophagy via suppressing IDH2 expression. These findings identified the important mechanistic connection between mitomiRs and mitochondrial metabolism under Cu exposure, providing a new insight into Cu toxicology.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126899DOI Listing
August 2021

Copper exposure induces mitochondrial dynamic disorder and oxidative stress via mitochondrial unfolded protein response in pig fundic gland.

Ecotoxicol Environ Saf 2021 Oct 2;223:112587. Epub 2021 Aug 2.

College of Veterinary Medicine, South China Agriculture University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Cu is a metallic element that widely spread over in the environment, which have raised wide concerns about the potential toxic effects and public health threat. The objective of this study aimed to investigate the impression of copper (Cu)-triggered toxicity on mitochondrial dynamic, oxidative stress, and unfolded protein response (UPR) in fundic gland of pigs. Weaned pigs were randomly distributed into three groups, fed with different Cu of 10 mg/kg (control group), 125 mg/kg (group I), and 250 mg/kg (group Ⅱ). The trial persisted for 80 days and the fundic gland tissues were collected for further researches. Moreover, the markers participated to mitochondrial dynamic, UPR,and oxidative stress in fundic gland were determined. Results revealed that vacuolar degeneration were observed in the treated groups contrast with control group, and the Cu level was boosted with the increasing intake of Cu. Besides that, the levels of CAT, TRX, HO, and GPDH were reduced in group Ⅰ and group Ⅱ, the mRNA levels of NRF2, HO-1, SOD-1, CAT, SOD-2, GSR, GPX1, GPX4, and TRX in the treated groups were promoted contrast to control group. Furthermore, the protein expression of KEAP1 was dramatically decreased, and the protein expression of NRF2, TRX and HO-1 were markedly enhanced in group Ⅰ and Ⅱ at 80 days. Moreover, the mRNA and protein expression levels of MFN1, MFN2, and OPA1 down-regulated and protein level of DRP1 was increased with the adding levels of Cu. Nevertheless, the UPR-related mRNA levels of CLPP, HTRA-2, CHOP, HSP10, and HSP60 were enhanced dramatically in Cu treatment group compared with control group. In general, our current study demonstrated that excessive absorption of Cu in fundic gland were related with stimulating UPR, oxidative stress, and the NRF2 interceded antioxidant defense. These results could afford an updated evidence on molecular theory of Cu-invited toxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112587DOI Listing
October 2021

The potential risks of herbicide butachlor to immunotoxicity via induction of autophagy and apoptosis in the spleen.

Chemosphere 2021 Jul 26;286(Pt 1):131683. Epub 2021 Jul 26.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1β, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131683DOI Listing
July 2021

Exposure to the herbicide butachlor activates hepatic stress signals and disturbs lipid metabolism in mice.

Chemosphere 2021 Nov 15;283:131226. Epub 2021 Jun 15.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Butachlor is a systemic herbicide widely applied on wheat, rice, beans, and different other crops, and is frequently detected in groundwater, surface water, and soil. Therefore, it is necessary to investigate the potential adverse health risks and the underlying mechanisms of hepatotoxicity caused by exposure to butachlor in invertebrates, other nontarget animals, and public health. For this reason, a total of 20 mice were obtained and randomly divided into two groups. The experimental mice in one group were exposed to butachlor (8 mg/kg) and the mice in control group received normal saline. The liver tissues were obtained from each mice at day 21 of the trial. Results indicated that exposure to butachlor induced hepatotoxicity in terms of swelling of hepatocyte, disorders in the arrangement of hepatic cells, increased concentrations of different serum enzymes such as alkaline phosphate (ALP) and aspartate aminotransferase (AST). The results on the mechanisms of liver toxicity indicated that butachlor induced overexpression of Apaf-1, Bax, Caspase-3, Caspase-9, Cyt-c, p53, Beclin-1, ATG-5, and LC3, whereas decreases the expression of Bcl-2 and p62 suggesting abnormal processes of apoptosis and autophagy. Results on different metabolites (61 differential metabolites) revealed upregulation of PE and LysoPC, whereas downregulation of SM caused by butachlor exposure in mice led to the disruption of glycerophospholipids and lipid metabolism in the liver. The results of our experimental research indicated that butachlor induces hepatotoxic effects through disruption of lipid metabolism, abnormal mechanisms of autophagy, and apoptosis that provides new insights into the elucidation of the mechanisms of hepatotoxicity in mice induced by butachlor.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131226DOI Listing
November 2021

Copper induces mitochondria-mediated apoptosis via AMPK-mTOR pathway in hypothalamus of Pigs.

Ecotoxicol Environ Saf 2021 Sep 5;220:112395. Epub 2021 Jun 5.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112395DOI Listing
September 2021

An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip.

Bioact Mater 2021 Dec 15;6(12):4580-4590. Epub 2021 May 15.

Yaneng Biotech, Co., Ltd, Fosun Pharma, Shenzhen 518100, China.

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. However, cleavage of the amplicons and primers by the - and -activity of Cas12a hinders the attempts to integrate the amplification and detection into a single reaction. Through phosphorothioate modification of primers, we realized onepot detection with high sensitivity using plasmids of SARS-CoV-2, HPV16 and HPV18. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, the reaction time required for a lateral-flow readout was significantly reduced. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized gold-nanopaticle strip, the readout was greatly enhanced owing to the elimination of the nonspecific signal. This established system, termed argeting DNA by Cas12a-based ye ight esting in an nepot eaction (TESTOR), was validated using clinical cervical scrape samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141609PMC
December 2021

Arsenic (III) and/or Antimony (III) induced disruption of calcium homeostasis and endoplasmic reticulum stress resulting in apoptosis in mice heart.

Ecotoxicol Environ Saf 2021 Sep 4;220:112394. Epub 2021 Jun 4.

Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with AsO (4 mg/kg), SbCl (15 mg/kg) and co-treat with SbCl (15 mg/kg) and AsO (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112394DOI Listing
September 2021

Arsenic exposure induces intestinal barrier damage and consequent activation of gut-liver axis leading to inflammation and pyroptosis of liver in ducks.

Sci Total Environ 2021 Sep 15;788:147780. Epub 2021 May 15.

College of Veterinary Medicine, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Arsenic is an important hazardous metalloid commonly found in polluted soil, rivers and groundwater. However, few studies exist regarding the effect of arsenic trioxide (ATO) on the gut-liver axis and consequent hepatotoxicity in waterfowl. Here, we investigated the influence of ATO on duck intestines and livers, and explored the role of the gut-liver axis in ATO-induced hepatotoxicity and intestinal toxicity. Our results demonstrated that ATO-exposure induced intestinal damage, liver inflammatory cell infiltration and vesicle steatosis. Additionally, the intestinal microbiota community in ATO-exposed ducks displayed significantly decreased α-diversity and an altered bacterial composition. Moreover, ATO-exposure markedly reduced the expression of intestinal barrier-related proteins (Claudin-1, MUC2, ZO-1 and Occludin), resulting in increased intestinal permeability and elevated lipopolysaccharide levels. Simultaneously, ATO-exposure also upregulated pyroptosis-related index levels in the liver and jejunum, and increased pro-inflammatory cytokine production (IFN-γ, TNF-α, IL-18, and IL-1β). Our further mechanistic studies showed that ATO-induced liver and jejunum inflammation were provoked by the activation of the LPS/TLR4/NF-κB signaling pathway and NLRP3 inflammasome. In summary, these results manifested that ATO exposure can cause liver and jejunal inflammation and pyroptosis, and the indirect gut-liver axis pathway may play an essential role in the potential mechanism of ATO-induced hepatotoxicity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147780DOI Listing
September 2021

Metabolomics and transcriptomics indicated the molecular targets of copper to the pig kidney.

Ecotoxicol Environ Saf 2021 May 1;218:112284. Epub 2021 May 1.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Copper poses huge environmental and public health concerns due to its widespread and persistent use in the past several decades. Although it is well established that at higher levels copper causes nephrotoxicity, the exact mechanisms of its toxicity is not fully understood. Therefore, this experimental study for the first time investigates the potential molecular mechanisms including transcriptomics, metabolomics, serum biochemical, histopathological, cell apoptosis and autophagy in copper-induced renal toxicity in pigs. A total of 14 piglets were randomly assigned to two group (7 piglets per group) and treated with a standard diet (11 mg CuSO per kg of feed) and a high copper diet (250 mg CuSO per kg of feed). The results of serum biochemical tests and renal histopathology suggested that 250 mg/kg CuSO in the diet significantly increased serum creatinine (CREA) and induced renal tubular epithelial cell swelling. Results on transcriptomics and metabolomics showed alteration in 804 genes and 53 metabolites in kidneys of treated pigs, respectively. Combined analysis of transcriptomics and metabolomics indicated that different genes and metabolism pathways in kidneys of treated pigs were involved in glycerophospholipids metabolism and glycosphingolipid metabolism. Furthermore, copper induced mitochondrial apoptosis characterized by increased bax, bak, caspase 3, caspase 8 and caspase 9 expressions while decreased bcl-xl and bcl2/bax expression. Exposure to copper decreased the autophagic flux in terms of increased number of autophagosomes, beclin1 and LC3b/LC3a expression and p62 accumulation. These results indicated that the imbalance of glycosphingolipid metabolism, the impairment of autophagy and increase mitochondrial apoptosis play an important role in copper induced renal damage and are useful mechanisms to understand the mechanisms of copper nephrotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112284DOI Listing
May 2021

Long-term exposure to the fluoride blocks the development of chondrocytes in the ducks: The molecular mechanism of fluoride regulating autophagy and apoptosis.

Ecotoxicol Environ Saf 2021 Jul 14;217:112225. Epub 2021 Apr 14.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112225DOI Listing
July 2021

Environmental fluoride exposure disrupts the intestinal structure and gut microbial composition in ducks.

Chemosphere 2021 Aug 19;277:130222. Epub 2021 Mar 19.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Fluorine (F) and its compounds produced from industrial production and coal combustion can cause air, water and soil contamination, which can accumulate in animals, plants and humans via food chain threatening public health. Fluoride exposure affects liver, kidney, gastrointestinal and reproductive system in humans and animals. Literature regarding fluoride influence on intestinal structure and microbiota composition in ducks is scarce. This study was designed to investigate these effects by using simple and electron microscopy and 16S rRNA sequencing techniques. Results indicated an impaired structure with reduced relative distribution of goblet cells in the fluoride exposed group. Moreover, the gut microbiota showed a significant decrease in alpha diversity. Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in both control and fluoride-exposed groups. Specifically, fluoride exposure resulted in a significant decrease in the relative abundance of 9 bacterial phyla and 15 bacterial genera. Among them, 4 phyla (Latescibacteria, Dependentiae, Zixibacteria and Fibrobacteres) and 4 genera (Thauera, Hydrogenophaga, Reyranella and Arenimonas) weren't even detectable in the gut microbiota of the ducks. In summary, higher fluoride exposure can significantly damage the intestinal structure and gut microbial composition in ducks.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130222DOI Listing
August 2021

Metabolomics analysis reveals the effect of copper on autophagy in myocardia of pigs.

Ecotoxicol Environ Saf 2021 Apr 18;213:112040. Epub 2021 Feb 18.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Among different synthetic compounds copper (Cu) is persistently and frequently used as growth promoter, antibacterial, antifungal and antiparasitic agent and has become common environmental pollutant. Therefore, this study explores the cardio-toxic effects of control group (10 mg/kg bw Cu) and treatment group (125 and 250 mg/kg bw Cu), and it association with process of autophagy and metabolomics in myocardium of pigs kept in three different experimental treatments for a period of 80 days. The results of serum biochemical parameters showed a significantly increase in creatinine kinase (CK), creatine kinase-MB (CK-MB), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and aspartate aminotransferase (AST) in pigs exposed to 125 mg/kg bw and 250 mg/kg bw Cu. Meanwhile, the severe structural abnormalities in cardiomyocytes were found when exposed to 250 mg/kg Cu at day 80. In addition, the mRNA and proteins (Beclin1, ATG5 and LC3II) expression levels were significantly increased and p62 was significantly decreased in cardiomyocytes exposed to 250 mg/kg Cu at day 80 of the trial. Further, UPLC-QTOF/MS technique showed that 7 metabolites were up-regulated and 37 metabolites were down-regulated in cardiomyocytes after 250 mg/kg Cu treatment, with a principal impact on the metabolic pathways including glycerophospholipid metabolism, one carbon pool by folate, fatty acid elongation and fatty acid degradation, which were related to autophagy. Overall, our study identified the autophagy processes and metabolites in metabolic pathways in Cu-induced myocardium injury, which provided useful evidence of myocardium toxicity caused by Cu exposure via metabolomics and multiple bioanalytic methods.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112040DOI Listing
April 2021

Acetyl-L-Carnitine Induces Autophagy to Promote Mouse Spermatogonia Cell Recovery after Heat Stress Damage.

Biomed Res Int 2021 18;2021:8871328. Epub 2021 Jan 18.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 M ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.
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http://dx.doi.org/10.1155/2021/8871328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837762PMC
May 2021

Exposure to copper induces mitochondria-mediated apoptosis by inhibiting mitophagy and the PINK1/parkin pathway in chicken (Gallus gallus) livers.

J Hazard Mater 2021 04 19;408:124888. Epub 2020 Dec 19.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), a transition metal with essential cellular functions, exerts toxic effects when present in excess by inducing oxidative stress. However, the Cu-induced crosstalk between mitophagy and apoptosis and the underlying mechanisms are unknown. Here, the mechanism of Cu-induced hepatotoxicity mediated by mitophagy and apoptosis was explored in vivo and in vitro. In in vivo experiments, chickens were fed a diet with various levels of Cu (11, 110, 220, and 330 mg/kg) for 7 weeks, which led to ultrastructural damage, mitophagy, and apoptosis in liver tissue. In vitro experiments on primary chicken hepatocytes showed that Cu treatment for 24 h increased the numbers of mitophagosomes and upregulated PINK1, parkin, and p62 mRNA levels and parkin and p62 protein levels, inducing mitophagy. Moreover, treatment with 3- methyladenine (3-MA) aggravated Cu-induced S-phase arrest in cell cycle; increased the apoptotic rate; increased p53, Bak1, Bax, Cyt C, and Caspase3/cleaved-caspase3 mRNA and protein levels; and decreased Bcl2 mRNA and protein levels. However, rapamycin (Rapa) had the opposite effects on the above factors. In general, the results reveal that Cu exposure can cause mitophagy through the PINK1/Parkin pathway in chicken livers, and that mitophagy might attenuate Cu-induced mitochondrial apoptosis.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124888DOI Listing
April 2021

Rapid detection of SARS-CoV-2 with CRISPR-Cas12a.

PLoS Biol 2020 12 15;18(12):e3000978. Epub 2020 Dec 15.

Yaneng Biotech Co. Ltd., Fosun Pharma, Shenzhen, China.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1-10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.
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http://dx.doi.org/10.1371/journal.pbio.3000978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737895PMC
December 2020

Copper induces energy metabolic dysfunction and AMPK-mTOR pathway-mediated autophagy in kidney of broiler chickens.

Ecotoxicol Environ Saf 2020 Dec 30;206:111366. Epub 2020 Sep 30.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address:

To explore the effects of copper (Cu) on energy metabolism and AMPK-mTOR pathway-mediated autophagy in kidney, a total of 240 one-day-old broiler chickens were randomized into four equal groups and fed on the diets with different levels of Cu (11, 110, 220, and 330 mg/kg) for 49 d. Results showed that excess Cu could induce vacuolar degeneration and increase the number of autophagosomes in kidney, and the adenosine triphosphate (ATP) level and mRNA levels of energy metabolism-related genes were decreased with the increasing dietary Cu level. Moreover, immunohistochemistry and immunofluorescence showed that the positive expressions of Beclin1 and LC3-II were mainly located in cytoplasm of renal tubular epithelial cells and increased significantly with the increasing levels of Cu. The mRNA levels of Beclin1, Atg5, LC3-I, LC3-II, Dynein and the protein levels of Beclin1, Atg5, LC3-II/LC3-I and p-AMPKα1/AMPKα1 were markedly elevated in treated groups compared with control group (11 mg/kg Cu). However, the mRNA and protein levels of p62 and p-mTOR/mTOR were significantly decreased with the increasing levels of Cu. These results suggest that impaired energy metabolism induced by Cu may lead to autophagy via AMPK-mTOR pathway in kidney of broiler chickens.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111366DOI Listing
December 2020

Copper induces oxidative stress with triggered NF-κB pathway leading to inflammatory responses in immune organs of chicken.

Ecotoxicol Environ Saf 2020 Sep 22;200:110715. Epub 2020 May 22.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address:

Copper (Cu) is a necessary trace mineral due to its biological activity. Excessive Cu can induce inflammatory response in humans and animals, but the underlying mechanism is still unknown. Here, 240 broilers were used to study the effects of excessive Cu on oxidative stress and NF-κB-mediated inflammatory responses in immune organs. Chickens were fed with diet containing different concentrations of Cu (11, 110, 220, and 330 mg of Cu/kg dry matter). The experiment lasted for 49 days. Spleen, thymus, and bursa of Fabricius (BF) on day 49 were collected for histopathological observation and assessment of oxidative stress status. Additionally, the mRNA and protein levels of NF-κB and inflammatory cytokines were also analyzed. The results indicated that excess Cu could increase the number and area of splenic corpuscle as well as the ratio of cortex and medulla in thymus and BF. Furthermore, excessive Cu intake could decrease activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); but increase contents of malondialdehyde (MDA), TNF-α, IL-1, IL-1β; up-regulate mRNA levels of TNF-α, IFN-γ, IL-1, IL-1β, IL-2, iNOS, COX-2, NF-κB and protein levels of TNF-α, IFN-γ, NF-κB, p-NF-κB in immune organs. In conclusion, excessive Cu could cause pathologic changes and induce oxidative stress with triggered NF-κB pathway, and might further regulate the inflammatory response in immune organs of chicken.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110715DOI Listing
September 2020

lncRNA ZFAS1 Is Involved in the Proliferation, Invasion and Metastasis of Prostate Cancer Cells Through Competitively Binding to miR-135a-5p.

Cancer Manag Res 2020 13;12:1135-1149. Epub 2020 Feb 13.

Department of Histology and Embryology, Guilin Medical University, Guilin, Guangxi, People's Republic of China.

Background: Prostate cancer (PCa) is a common malignant tumor in men. lncRNA ZFAS1 plays a carcinogenic role in many types of cancer; however, its potential role in PCa remains unclear. The current study aimed to determine the expression and function of ZFAS1 in PC.

Methods: The ZFAS1 expression in PC tissues and cells was determined by quantitative polymerase chain reaction (qPCR). SiZFAS1, miR-135a-5p mimic and miR-135a-5p inhibitor were transfected into PCa cells. The direct target of ZFAS1 was predicted by Starbase and verified by dual-luciferase reporter. Cell viability, proliferation, apoptosis, migration and invasion of the PCa cells were determined by cell counting kit-8, clone formation assay, flow cytometer, scratch and Transwell assay, respectively. The expression levels of related proteins and mRNAs were determined by Western blotting and qPCR.

Results: ZFAS1 expression was up-regulated in PCa cells and tissues. ZFAS1 could competitively bind to miR-135a-5p in PCa cells, and down-regulation of ZFAS1 inhibited cell viability, proliferation, migration, invasion of PCa cells and the occurrence of epithelial-mesenchymal transformation (EMT) and promoted apoptosis of PCa cells and increased the miR-135a-5p expression. Moreover, the function of miR-135a-5p mimic in PCa cells was consistent with ZFAS1 knockdown, while the function of miR-135a-5p inhibitor was opposite to that of miR-135a-5p mimic in PCa cells. The results showed that knocking down ZFAS1 could attenuate the effects of miR-135a-5p inhibitor on cell proliferation, invasion and EMT of PCa cells.

Conclusion: Knocking down ZFAS1 could inhibit the proliferation, invasion and metastasis of PCa cells through regulating miR-135a-5p expression.
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http://dx.doi.org/10.2147/CMAR.S237439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025677PMC
February 2020

Long-term exposure to copper induces autophagy and apoptosis through oxidative stress in rat kidneys.

Ecotoxicol Environ Saf 2020 Mar 6;190:110158. Epub 2020 Jan 6.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl (15 [control], 30, 60, or 120 mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys.
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http://dx.doi.org/10.1016/j.ecoenv.2019.110158DOI Listing
March 2020

Effects of copper on oxidative stress and autophagy in hypothalamus of broilers.

Ecotoxicol Environ Saf 2019 Dec 26;185:109710. Epub 2019 Sep 26.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China. Electronic address:

The purpose of this research was to discuss the effects of copper (Cu)-induced toxicity on oxidative stress and autophagy in hypothalamus of broilers. In this study, 240 one-day-old broilers were randomly divided into 4 groups and the contents of dietary Cu in 4 groups were 11 mg/kg (control group), 110 mg/kg (group I), 220 mg/kg (group II), and 330 mg/kg (group III). The experiment lasted for 49 days and the hypothalamus tissues were collected for histological observation and detection of Cu content. Additionally, the indicators related to oxidative stress in hypothalamus were determined. Moreover, the mRNA expression levels of autophagy-related genes and the protein expression levels of Beclin1, LC3-II/LC3-I, and p62 in hypothalamus were measured. Results showed that the treated groups were observed vacuolar degeneration in hypothalamus compared to control group, and the Cu content in hypothalamus was increased with the increase of dietary Cu. Furthermore, the activities of SOD, CAT, T-AOC were increased in group I and group II and then decreased in group III, and the content of MDA and the mRNA levels of Nrf2, HO-1, SOD-1, CAT, GCLC, GCLM, and GST in treated groups were elevated compared to control group. Moreover, the mRNA expression levels of Beclin1, Atg5, LC3-I, LC3-II and the protein expression levels of Beclin1 and LC3-II/LC3-I up-regulated significantly with the increasing levels of Cu. However, the mRNA expression levels of p62 and mTOR and the protein expression level of p62 down-regulated remarkably. Taken together, our present study evidenced that excessive intake of Cu could induce oxidative stress and autophagy in hypothalamus of broilers.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109710DOI Listing
December 2019

Methionine Sulfoxide Reductases Are Related to Arsenic Trioxide-Induced Oxidative Stress in Mouse Liver.

Biol Trace Elem Res 2020 Jun 31;195(2):535-543. Epub 2019 Aug 31.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.

Arsenic trioxide (ATO), a trivalent arsenic compound, is known to disrupt redox homeostasis. Methionine sulfoxide reductases (Msrs), a group of antioxidant proteins, convert methionine sulfoxide back to methionine in living organisms exposed to oxidative stress. The objective of this study was to determine the effects of ATO on oxidative stress and the expressions of Msrs in mouse liver. Sixty male mice were randomly divided into six equal groups: one control group and five groups that received ATO treatment (0.3, 1, 3, 6, and 9 mg/kg, respectively). After a 4-week treatment, livers specimens were collected and assayed for malonyldialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) activity. In addition, the mRNA expressions of SOD-1 and HO-1 and the mRNA and protein expressions of Msrs were also determined. Results showed that the T-AOC activity, SOD activity, and SOD-1 mRNA expression were significantly decreased (P < 0.01), while the GSH-Px level, MDA content, and HO-1 mRNA expression were significantly increased in mice treated with ATO compared with control. Levels of MsrB2 mRNA and MsrA protein were significantly increased by ATO treatment, except in the highest dose group. There were no significant changes in MsrB3 mRNA level. ATO, at 1 or 3 mg/kg, increased MsrB1 expression. Modifications in MsrA protein level were consistent with changes in mRNA levels. Collectively, our results suggest that ATO induced oxidative stress and then led to the variations in Msrs activity in mouse liver.
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http://dx.doi.org/10.1007/s12011-019-01881-6DOI Listing
June 2020

Characterization of the cellular effects and mechanism of arsenic trioxide-induced hepatotoxicity in broiler chickens.

Toxicol In Vitro 2019 Dec 20;61:104629. Epub 2019 Aug 20.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

To characterize the cellular effects and mechanism of arsenic trioxide (ATO)-induced hepatotoxicity in broiler chickens, increasing concentrations of ATO (0, 0.6, 1.2, 2.4, and 4.8 μM) were added to chicken hepatocyte cultures in vitro. The changes in hepatocyte morphology, oxidative stress and apoptosis were evaluated using fluorescence microscopy and flow cytometry. The effects of ATO on mRNA or protein expression of antioxidant enzymes, especially methionine sulfoxide reductase (Msr), were analyzed using qRT-PCR and western blotting assays. Increased apoptosis were concomitant with increased reactive oxygen species (ROS) accumulation and upregulation of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) with increasing ATO concentrations. Moreover, G phase arrest and dysregulation of the balance between antiapoptotic versus proapoptotic factors were noted. Furthermore, upregulation of HO-1, SOD-1, and TRX in the ATO groups were consistent with ATO-induced oxidative damage. High Msr, SOD-1, TRX, Bak1, Bax, and p53 protein levels in the ATO groups indicate that these proteins may have accumulated to counter ATO-induced oxidative stress. ROS scavenger N-acetyl-l-cysteine (NAC) could reverse ATO-induced oxidative damage and restore hepatocyte viability, even with compromised Msr function. Our findings suggest that Msr can protect broiler hepatocytes against ATO-induced oxidative stress. Furthermore, NAC-mediated reversal of oxidative damage may represent a strategy to mitigate potential economic losses associated with arsenic poisoning in the poultry industry.
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http://dx.doi.org/10.1016/j.tiv.2019.104629DOI Listing
December 2019

Effect of a background Ca entry pathway mediated by TRPC1 on myocardial damage of broilers with induced ascites syndrome.

Avian Pathol 2019 Oct 19;48(5):429-436. Epub 2019 Jul 19.

College of Veterinary Medicine, South China Agricultural University , Guangzhou , P. R. People's Republic of China.

Ascites syndrome (AS) in chickens is associated with profound vascular remodelling and increased pulmonary artery pressure as well as right ventricular hypertrophy. Classical transient receptor potential cation channels (TRPCs) are key regulators of cardiac hypertrophy that act regulation of calcium influx in mammals. We investigated whether classical transient receptor potential channels in chickens with right ventricular hypertrophy still possess this mechanism for regulating Ca flux. Intravenous injection of cellulose particles was successfully used to induce AS in chickens, and tissues were examined 22 days after treatment. The chickens in the test group showed cardiac hypertrophy with oedema of the cardiac muscle and disruption of myofilaments. The right-to-total ventricle weight ratio (RV/TV), the levels of serum aspartate aminotransferase (AST) and creatine kinase (CK) of the test group were significantly higher than in the control group. Intracellular calcium levels were significantly increased in cardiomyocytes from chickens in the test group. Gene expression of TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7 in heart tissues from the test group showed no significant differences compared with controls. However, TRPC1 protein levels, as well as mRNA levels, were down-regulated in the heart muscle of AS chickens ( < 0.05). Although we observed an increase in calcium concentration, the expression of TRPC1 decreased in cardiac cells. We hypothesized that an increase in intracellular free calcium concentration could inversely regulate calcium channel expression. Intracellular Ca levels were increased in the myocardium of AS broilers. Expression of TRPC1, which mediates calcium influx, was decreased in the myocardium of AS broilers. The relationship between intracellular Ca levels and expression of TRPC1 requires further study.
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http://dx.doi.org/10.1080/03079457.2019.1617834DOI Listing
October 2019

Inhibition of Caspase-1-dependent pyroptosis attenuates copper-induced apoptosis in chicken hepatocytes.

Ecotoxicol Environ Saf 2019 Jun 26;174:110-119. Epub 2019 Feb 26.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China.

The purpose of this study was to investigate the effects of copper (Cu) on hepatocyte pyroptosis and the relationship between pyroptosis and apoptosis in the mechanisms of Cu toxicity. Primary chicken hepatocytes were cultured in different concentrations of Cu sulfate (CuSO) (0, 10, 50, and 100 μM), N-acetylcysteine (NAC) (1 mM), and Z-YVAD-fluoromethylketone (Z-YVAD-FMK) (10 μM) for 24 h, and the combination of Cu and NAC or Z-YVAD-FMK for 24 h. Cellular morphology and function, cell viability, mitochondria membrane potential (MMP), apoptosis rate, mRNA expression of pyroptosis-related and apoptosis-related genes, and Caspase-1, Caspase-3 proteins expression were determined. These results indicated that Cu markedly induced the mRNA expression of pyroptosis-related genes (Caspase-1, IL-1β, IL-18, and NLRP3) and Caspase-1 protein expression. Furthermore, contents of Caspase-1, IL-1β, and IL-18 in the supernatant fluid of culture hepatocytes were significantly increased in hepatocytes. NAC relieved excess Cu-caused the changes of above genes and proteins. Additionally, Z-YVAD-FMK, caspase-1 inhibitor, which attenuated Cu-induced the increased lactic dehydrogenase (LDH), aspartate amino transferase (AST), alanine aminotransferase (ALT) activities. Furthermore, treatment with Cu and Z-YVAD-FMK could down-regulate the mRNA levels of Caspase-3, Bak1, Bax, and CytC and Caspase-3 protein expression, up-regulate the mRNA expression of Bcl2, increase the MMP and reduce cell apoptosis compared to treatment with Cu in hepatocytes. Collectively, these finding evidenced that excess Cu induced pyroptosis by generating ROS in hepatocytes, and the inhibition of Caspase-1-dependent pyroptosis might attenuate Cu-induced apoptosis.
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http://dx.doi.org/10.1016/j.ecoenv.2019.02.069DOI Listing
June 2019

Copper induces oxidative stress and apoptosis through mitochondria-mediated pathway in chicken hepatocytes.

Toxicol In Vitro 2019 Feb 30;54:310-316. Epub 2018 Oct 30.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

The aim of this study was to investigate the effects of excessive copper (Cu)-induced cytotoxicity on oxidative stress and mitochondrial apoptosis in chicken hepatocytes. Chicken hepatocytes were cultured in medium in the absence and presence of copper sulfate (CuSO) (10, 50, 100 μM), in N-acetyl-L-cysteine (NAC) (1 mM), and the combination of CuSO and NAC for 24 h. Morphologic observation and function, reactive oxygen species (ROS) level, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and apoptosis-related mRNA and protein levels were determined. These results indicated that excessive Cu could induce release of intracellular lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); increase levels of ROS, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), lipid peroxidation (LPO), and NO; decrease glutathione (GSH) content and MMP; upregulated Bak1, Bax, CytC, and Caspase3 mRNA and protein expression, inhibited Bcl2 mRNA and protein expression, and induced cell apoptosis in a dose effect. The Cu-caused changes of all above factors were alleviated by treatment with NAC. These results suggested that excessive Cu could induce oxidative stress and apoptosis via mitochondrial pathway in chicken hepatocytes.
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http://dx.doi.org/10.1016/j.tiv.2018.10.017DOI Listing
February 2019

Autophagy attenuates copper-induced mitochondrial dysfunction by regulating oxidative stress in chicken hepatocytes.

Chemosphere 2018 Aug 29;204:36-43. Epub 2018 Mar 29.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h. Results showed that Cu could markedly increase the number of autophagosomes and LC3 puncta, induce autophagy-related genes (Beclin1, ATG5, LC3Ⅰ, LC3Ⅱ, mTOR, and Dynein) mRNA expression and proteins (BECN1, LC3Ⅱ/LC3Ⅰ) expression. NAC could relieve Cu-induced the changes of above genes and proteins. Additionally, rapamycin attenuated Cu-induced the increased lactic dehydrogenase (LDH), aspartate amino transferase (AST), and alanine aminotransferase (ALT) activities, and SOD-1 mRNA expression as well as the decreased cell viability, reactive oxygen species (ROS), hydrogen peroxide, total superoxide dismutase (T-SOD), malonaldehyde (MDA), catalase (CAT), HO-1 mRNA expression, adenosine triphosphate (ATP) levels, mitochondrial mass, and mitochondria membrane potential (MMP). But 3-MA had the opposite effects on above factors. Collectively, these findings provide strong evidence that Cu could induce autophagy by generating excessive ROS in hepatocytes, and autophagy might attenuate Cu-induced mitochondrial dysfunction by regulating oxidative stress.
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http://dx.doi.org/10.1016/j.chemosphere.2018.03.192DOI Listing
August 2018

Liver mitochondrial dysfunction and electron transport chain defect induced by high dietary copper in broilers.

Poult Sci 2017 Sep;96(9):3298-3304

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, P. R. China. Electronic address:

Copper is an important trace mineral in the diet of poultry due to its biological activity. However, limited information is available concerning the effects of high copper on mitochondrial dysfunction. In this study, 72 broilers were used to investigate the effects of high dietary copper on liver mitochondrial dysfunction and electron transport chain defect. Birds were fed with different concentrations [11, 110, 220, and 330 mg of copper/kg dry matter (DM)] of copper from tribasic copper chloride (TBCC). The experiment lasted for 60 d. Liver tissues on d 60 were subjected to histopathological observation. Additionally, liver mitochondrial function was recorded on d 12, 36, and 60. Moreover, a site-specific defect in the electron transport chain in liver mitochondria was also identified by using various chemical inhibitors of mitochondrial respiration. The results showed different degrees of degeneration, mitochondrial swelling, and high-density electrons in hepatocytes. In addition, the respiratory control ratio (RCR) and oxidative phosphorylation rate (OPR) in liver mitochondria increased at first and then decreased in high-dose groups. Moreover, hydrogen peroxide (H2O2) generation velocity in treated groups was higher than that in control group, which were magnified by inhibiting electron transport at Complex IV. The results indicated that high dietary copper could decline liver mitochondrial function in broilers. The presence of a site-specific defect at Complex IV in liver mitochondria may be responsible for liver mitochondrial dysfunction caused by high dietary copper.
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http://dx.doi.org/10.3382/ps/pex137DOI Listing
September 2017

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets.

Int J Mol Sci 2016 Jul 15;17(7). Epub 2016 Jul 15.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Dietary selenium putatively prevents oxidative damage, whereas excessive selenium may lead to animal disorder. In this study, we investigated the effects of low and excessive levels of dietary selenium on oxidative stress and mitochondrial proteins in mouse liver. Six to eight week old mice were fed a diet with low, excessive, or moderate (control) levels of selenium (sodium selenite). The selenium concentration and oxidative stress-related parameters in hepatic mitochondria were evaluated. Two-dimensional electrophoresis and mass spectrometry were applied to identify the differentially-expressed proteins associated with dietary selenium. The selenium content of the livers in mice with the low selenium diet was significantly lower than that of the control, while that of mice fed excessive levels was significantly higher. In both groups oxidative stress in hepatic mitochondria was found; accompanied by lower superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels and higher malondialdehyde (MDA) content, compared with the control group. Furthermore, ten proteins in the hepatic mitochondria of the selenium-low or -excessive groups with more than two-fold differences in abundance compared with the control group were identified. The differentially-expressed proteins in hepatic mitochondria may be associated with dietary (low or excessive) selenium-induced oxidative stress.
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http://dx.doi.org/10.3390/ijms17071137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964510PMC
July 2016

Erratum to: A redesigned CRISPR/Cas9 system for marker-free genome editing in Plasmodium falciparum.

Parasit Vectors 2016 05 17;9(1):288. Epub 2016 May 17.

Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou, 510530, Guangdong Province, China.

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http://dx.doi.org/10.1186/s13071-016-1580-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870775PMC
May 2016
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