Publications by authors named "Guoliang Hu"

89 Publications

Case Report: Combination Therapy With PD-1 Blockade for Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation Resulted in Fatal GVHD.

Front Immunol 2021 1;12:639217. Epub 2021 Apr 1.

Department of Hematology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.

Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of this monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and their ligands, making the combination of HMAs and immune checkpoint blockade therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation. We reported a case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT and was previously exposed to HMAs-based therapy. The patient received tislelizumab for compassionate use. After the combination treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease (MRD) by flow cytometry (FCM), and negative Wilms' tumor protein 1 (WT1). However, the patient successively developed serious immune-related adverse events (irAEs) and graft vs. host disease (GVHD) and eventually died from complications of GVHD. To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML posttransplantation. This report highlights the safety concerns of using an anti-PD-1 antibody in combination with azacitidine after allo-HSCT, especially the risk of GVHD, and provides a basis for future studies.
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http://dx.doi.org/10.3389/fimmu.2021.639217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047076PMC
April 2021

Preparation of the peroxisome proliferator-activated receptor α polyclonal antibody: Its application in fatty liver hemorrhagic syndrome.

Int J Biol Macromol 2021 Apr 7;182:179-186. Epub 2021 Apr 7.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Peroxisome proliferator-activated receptor α (PPARα) play a key role in the regulation of metabolic homeostasis, inflammation, cellular growth, and differentiation. To further explore the potential role of PPARα in the energy homeostasis of fatty liver hemorrhagic syndrome (FLHS), we reported the prokaryotic expression and purification of chicken PPARα subunit protein, and successfully prepared a polyclonal antibody against PPARα recombinant protein. The 987 bp PPARα subunit genes were cloned into the pEASY-T3 clone vector. Then the plasmid PCR products encoding 329 amino acids were ligated to pEASY-Blunt E2 vector and transformed into BL21 to induce expression. The recombinant PPARα subunit protein, containing His-tag, was purified by affinity column chromatography using Ni-NTA affinity column. Rabbit antiserum was generated by using the concentration of recombinant PPARα subunit protein as the antigen. The results of western blotting showed that the antiserum can specifically recognize chicken endogenous PPARα protein. Immunohistochemistry and immunofluorescence showed that the PPARα mainly existed in the nucleus of hepatocytes, renal epithelial cells and hypothalamic endocrine nerve cells. More importantly, western blotting and real-time quantitative PCR indicated that FLHS significantly decreased the expression of PPARα.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.018DOI Listing
April 2021

Development of Dermestes tessellatocollis Motschulsky under different constant temperatures and its implication in forensic entomology.

Forensic Sci Int 2021 Apr 15;321:110723. Epub 2021 Feb 15.

Department of Forensic Medicine, Soochow University, Ganjiang East Road, Suzhou, China.

Dermestidae generally appears on dry corpses and carcasses, especially if mummified or skeletonized. They are forensically important insect species for estimating longer postmortem intervals (PMI). As they develop, Dermestidae larvae undergo multiple larval ecdyses; however, a lack of guidelines for determining the larval instar limits their forensic application. Herein, we explored how temperature impacts the development of Dermestes tessellatocollis Motschulsky, 1860 (Coleoptera: Dermestidae). At seven constant temperatures (16, 19, 22, 25, 28, 31, and 34 °C), the developmental time from egg to adult was 163.87 ± 9.19, 103.56 ± 3.02, 63.59 ± 2.88, 51.49 ± 2.74, 47.86 ± 3.01, 44.62 ± 4.65, and 41.80 ± 4.87 days respectively. Four morphological indexes, including head capsule width, pronotum width, mesonotum width, and body length, were taken in vivo at regular intervals to identify methods for larval instar determination in D. tessellatocollis. The acquired morphological data were used to simulate fitted curves and equations depicting the relationship between the four morphological indexes and instars. From the validation experiment, we could hardly determine a specific instar based on the morphological indexes. The combination of morphometric data (head capsule, pronotum, and mesonotum width) generated the classification accuracy at 100%, 87.5%, 85%, and 93% for the 1st, 2nd/3rd, 4th/5th, and 6th/7th instars, respectively. Nevertheless, the accuracy was unsatisfactory for application in forensic casework. This study provides fundamental development data for adopting D. tessellatocollis in minimum postmortem interval (PMI) estimations; however, further studies are needed to improve the classification accuracy for the larval instar determination.
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http://dx.doi.org/10.1016/j.forsciint.2021.110723DOI Listing
April 2021

Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens.

Front Physiol 2021 9;12:590638. Epub 2021 Feb 9.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Fatty liver hemorrhage syndrome (FLHS), a nutritional and metabolic disease that frequently occurs in laying hens, causes serious losses to the poultry industry. Nowadays, the traditional clinical diagnosis of FLHS still has its limitations. Therefore, searching for some metabolic biomarkers and elucidating the metabolic pathway are useful for the diagnosis and prevention of FLHS. In the present study, a model of FLHS in laying hens induced by feeding a high-energy, low-protein diet was established. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the metabolites in serum at days 40 and 80. The result showed that, in total, 40 differential metabolites closely related to the occurrence and development of FLHS were screened and identified, which were mainly associated with lipid metabolism, amino acid metabolism, and energy metabolism pathway disorders. Further investigation of differential metabolites showed 10 potential biomarkers such as 3-hydroxybutyric acid, oleic acid, palmitoleic acid, and glutamate were possessed of high diagnostic values by analyzing receiver operating characteristic (ROC) curves. In conclusion, this study showed that the metabolomic method based on GC-TOF-MS can be used in the clinical diagnosis of FLHS in laying hens and provide potential biomarkers for early risk evaluation of FLHS and further insights into FLHS development.
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http://dx.doi.org/10.3389/fphys.2021.590638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900428PMC
February 2021

Nephropathogenic Infectious Bronchitis Virus Infection Altered the Metabolome Profile and Immune Function of the Bursa of Fabricius in Chicken.

Front Vet Sci 2020 21;7:628270. Epub 2021 Jan 21.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Infectious bronchitis is a highly contagious, acute viral respiratory disease of chickens, regardless of the strain, and its infection may lead to considerable economic losses to the poultry industry. New nephropathogenic infectious bronchitis virus (NIBV) strains have increasingly emerged in recent years; hence, evaluating their infection-influenced immune function changes and the alteration of metabolite profiling is important. Initially, chickens were randomly distributed into two groups: the control group (Con) and the disease group (Dis). Here, the partial cytokines were examined, and the metabolome alterations of the bursa of Fabricius (BF) in NIBV infections in chickens were profiled by gas chromatography time-of-flight/mass spectrometry (GC-TOF/MS). The results revealed that the NIBV infection promotes the mRNA expression of inflammatory cytokines. Metabolic profile analysis indicated that clustering differed between the two groups and there were 75 significantly different metabolites detected between the two groups, suggesting that the host metabolism was significantly changed by NIBV infection. Notably, the following 12 metabolites were identified as the potential biomarkers: 3-phenyllactic acid, 2-deoxytetronic acid, aminomalonic acid, malonamide 5, uric acid, arachidonic acid, 2-methylglutaric acid, linoleic acid, ethanolamine, stearic acid, N-alpha-acetyl-l-ornithine, and O-acetylserine. Furthermore, the results of the correlation analysis showed that a strong correlation existed between metabolic biomarkers and inflammatory cytokines. Our results describe an immune and metabolic profile for the BF of chickens when infected with NIBV and provide new biomarkers of NIBV infection as potential targets and indicators of indicating therapeutic efficacy.
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http://dx.doi.org/10.3389/fvets.2020.628270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858655PMC
January 2021

Dysregulated expression of mRNA and SNP in pulmonary artery remodeling in ascites syndrome in broilers.

Poult Sci 2021 Mar 28;100(3):100877. Epub 2020 Nov 28.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, School of Land Resources and Environment, Key Laboratory of Agricultural Resource and Ecology in the Poyang Lake Basin of Jiangxi Province, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address:

Broiler ascites syndrome (AS), also called pulmonary artery hypertension, is a metabolic disorder that has been observed worldwide in fast-growing broilers. Pulmonary arterial remodeling is a key step in the development of AS. The precise relationship between mRNA and SNP of the pulmonary artery in regulating AS progression remains unclear. In this study, we obtained pulmonary artery tissues from broilers with AS to perform pathologic section and pathologic anatomic observation. SNP, InDel, and mRNA data analysis were carried out using GATK and ANNOVAR software to study the SNP loci of 985 previously reported genes (437 upregulated and 458 downregulated). The pathology results showed that there was a lot of yellow fluid in the abdominal cavity and pericardium, that the ascites cardiac index and hematocrit changed significantly, and that the pulmonary artery had remodeled and become thicker in the disease group. Myocardial sections showed vacuolar degeneration of myocytes and rupture of muscle fibers. In addition, ALDH7A1, IRG1, GGT5, IGSF1, DHX58, USP36, TREML2, SPAG1, CD34, and PLEKHA7 were found to be closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. Taken together, our present study further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression.
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http://dx.doi.org/10.1016/j.psj.2020.11.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936122PMC
March 2021

Activation of AMP-activated protein kinase signaling pathway ameliorates steatosis in laying hen hepatocytes.

Poult Sci 2021 Mar 4;100(3):100805. Epub 2020 Nov 4.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

The fatty liver hemorrhage syndrome in laying hens is a disease of lipid metabolism disorders. Importantly, energy sensor AMP-activated protein kinase (AMPK) plays an essential role in homeostasis regulation of liver lipid. The current research aims to investigate the relationship between AMPK signaling pathway and lipid metabolism in laying hen hepatocytes and explore the underlying mechanisms. The steatotic hepatocytes model of laying hen was established and treated with AMPK agonist AICAR and inhibitor compound C. The results showed that the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly declined while high-density lipoprotein cholesterol level increased in the AICAR-treated steatosis group compared with the steatosis group. Furthermore, the mRNA levels of liver kinase B1 and AMP-activated protein kinase α1 declined significantly in the steatosis group compared with those in the normal group. However, AMPK activation significantly upregulated the mRNA levels of peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase-1 while downregulated the mRNA levels of acetyl CoA carboxylase, fatty acid synthase, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, Sn-glycerol-3-phosphate acyltransferase, and hepatocyte nuclear factor 4α. These results suggest that activated AMPK signaling pathway increases fatty acid oxidation and reduces lipid synthesis in laying hen hepatocytes, thereby ameliorating liver steatosis.
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http://dx.doi.org/10.1016/j.psj.2020.10.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936166PMC
March 2021

Inhibition of ROS/NLRP3/Caspase-1 mediated pyroptosis attenuates cadmium-induced apoptosis in duck renal tubular epithelial cells.

Environ Pollut 2020 Oct 23;273:115919. Epub 2020 Oct 23.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China. Electronic address:

Cadmium (Cd) is an occupational and environmental pollutant, which mainly causes nephrotoxicity by damaging renal proximal tubular cells. To evaluate the effects of Cd on pyroptosis and the relationship between pyroptosis and apoptosis in duck renal tubular epithelial cells, the cells were cultured with 3CdSO·8HO (0, 2.5, 5.0, or 10.0 μM Cd), N-acetyl-L-cysteine (NAC) (100.0 μM), Z-YVAD-FMK (10.0 μM) or the combination of Cd and NAC or Z-YVAD-FMK for 12 h, and then cytotoxicity was assessed. The results evidenced that Cd significantly increased the releases of interleukin-18 (IL-18) and interleukin-1β (IL-1β), lactate dehydrogenase (LDH) and nitric oxide (NO), relative conductivity and cellular reactive oxygen species (ROS) level. Simultaneously, Cd also markedly upregulated NLRP3, Caspase-1, ASC, NEK7, IL-1β and IL-18 mRNA levels and NLRP3, Caspase-1 p20, GSDMD and ASC protein levels. Additionally, NAC notably improved the changes of above indicators induced by Cd. Combined treatment with Cd and Z-YVAD-FMK remarkably elevated Bcl-2 mRNA and protein levels, inhibited p53, Bax, Bak-1, Cyt C, Caspase-9 and Caspase-3 mRNA levels and p53, Bax, Bak-1, Caspase-9/cleaved Caspase-9 and Caspase-3/cleaved Caspase-3 protein levels, increased mitochondrial membrane potential (MMP), decreased apoptosis ratio and cell damage compared to treatment with Cd alone. Taken together, Cd exposure induces duck renal tubular epithelial cell pyroptosis through ROS/NLRP3/Caspase-1 signaling pathway, and inhibiting Caspase-1 dependent pyroptosis attenuates Cd-induced apoptosis.
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http://dx.doi.org/10.1016/j.envpol.2020.115919DOI Listing
October 2020

Cadmium and molybdenum co-induce pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells.

Environ Pollut 2021 Mar 30;272:116403. Epub 2020 Dec 30.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China. Electronic address:

Cadmium (Cd) and excess molybdenum (Mo) are harmful to animals, but the combined nephrotoxic mechanism of Cd and Mo in duck remains poorly elucidated. To assess joint effects of Cd and Mo on pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells, cells were cultured with 3CdSO·8HO (4.0 μM), (NH)MoO·4HO (500.0 μM), MCC950 (10.0 μM), BHA (100.0 μM) and combination of Cd and Mo or Cd, Mo and MCC950 or Cd, Mo and BHA for 12 h, and the joint cytotoxicity was explored. The results manifested that toxicity of non-equitoxic binary mixtures of Mo and Cd exhibited synergic interaction. Mo or/and Cd elevated ROS level, PTEN mRNA and protein levels, and decreased PI3K, AKT and p-AKT expression levels. Simultaneously, Mo or/and Cd upregulated ASC, NLRP3, NEK7, Caspase-1, GSDMA, GSDME, IL-18 and IL-1β mRNA levels and Caspase-1 p20, NLRP3, ASC, GSDMD protein levels, increased the percentage of pyroptotic cells, LDH, NO, IL-18 and IL-1β releases as well as relative conductivity. Moreover, NLRP3 inhibitor MCC950 and ROS scavenger BHA could ameliorate the above changed factors induced by Mo and Cd co-exposure. Collectively, our results reveal that combination of Mo and Cd synergistically cause oxidative stress and trigger pyroptosis via ROS/PTEN/PI3K/AKT axis in duck tubular epithelial cells.
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http://dx.doi.org/10.1016/j.envpol.2020.116403DOI Listing
March 2021

Cloning and prokaryotic expression of the chicken liver kinase B1 (LKB1) and its localization in liver, heart and hypothalamus.

Int J Biol Macromol 2021 Feb 29;169:513-520. Epub 2020 Dec 29.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Liver kinase B1 (LKB1) is a member of the serine/threonine kinase family, which plays an indispensable role in the organism of animals. In the current study, the chicken LKB1 protein gene was amplified by PCR based on the primers and cDNA templates. Then, the cloning vector was constructed and the target gene was cloned. After that, the target gene was inserted into the expression vector to construct the recombinant plasmid. The recombinant plasmid was transformed into BL21 (DE3) host cells and the LKB1 recombinant proteins were successfully expressed by using Isopropyl-β-D-thiogalactopyranoside (IPTG). Finally, purified LKB1 proteins were used as antigen and the rabbit-derived antiserums were collected. The antiserum titer determined by ELISA was not less than 1:128000. The results of Western blot suggested that the polyclonal antibody is highly specific to chicken LKB1 protein. Immunofluorescence indicated that the LKB1 protein is mainly expressed in the cytoplasm of liver, heart and hypothalamus cells of chicken. Our study showed that the LKB1 polyclonal antibodies produced by this method are effective and can be used to further study the role of LKB1 in the pathogenesis of chicken disease.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.195DOI Listing
February 2021

Inhibition of autophagy aggravates molybdenum-induced mitochondrial dysfunction by aggravating oxidative stress in duck renal tubular epithelial cells.

Ecotoxicol Environ Saf 2021 Feb 18;209:111771. Epub 2020 Dec 18.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China. Electronic address:

Excessive molybdenum (Mo) has adverse effects on animals. To elucidate the effects of autophagy on Mo-induced nephrotoxicity, the duck renal tubular epithelial cells were cultured in medium in absence and presence of (NH)MoO.4HO (0, 480, 720, 960 μM Mo), 3-Methyladenine (3-MA) (2.5 μM), and the combination of Mo and 3-MA for 12 h. After 12 h exposure, the MDC staining, morphologic observation, LC3 puncta, cell viability, autophagy-related genes mRNA and proteins levels, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, antioxidant indices, mitochondrial membrane potential (MMP), mitochondrial mass, mitochondrial respiratory control ratio (RCR) and oxidative phosphorylation rate (OPR) were determined. The results showed that excessive Mo exposure significantly elevated the number of autophagosome and LC3 puncta, upregulated Beclin-1, Atg5, LC3A and LC3B mRNA levels, and LC3II/LC3I and Beclin-1 protein levels, decreased mTOR, p62 and Dynein mRNA levels and p62 protein level. Besides, co-treatment with Mo and 3-MA dramatically increased LDH release, ROS level, hydrogen peroxide (HO) and malondialdehyde (MDA) contents as well as cell dam age, reduced cell viability, the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), MMP, mitochondrial mass, mitochondrial RCR and OPR compared to treatment with Mo alone. Taken together, these results suggest that excessive Mo exposure can induce autophagy in duck renal tubular epithelial cells, inhibition of autophagy aggravates Mo-induced mitochondrial dysfunction by regulating oxidative stress.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111771DOI Listing
February 2021

Activation of the ROS/HO-1/NQO1 signaling pathway contributes to the copper-induced oxidative stress and autophagy in duck renal tubular epithelial cells.

Sci Total Environ 2021 Feb 26;757:143753. Epub 2020 Nov 26.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China. Electronic address:

The aim of this study was to investigate the crosstalk between oxidative stress and autophagy through the ROS/HO-1/NQO1 pathway caused by copper (Cu). Duck renal tubular epithelial cells were treated in Cu sulfate (CuSO) (0, 100 and 200 μM) for 12 h, and in the combination of CuSO (200 μM) and reactive oxygen species (ROS) scavenger (butyl hydroxyanisole, BHA, 100 μM), or HO-1 inhibitor (zinc protoporphyrin, ZnPP, 10 μM) for 12 h. Results revealed that Cu could significantly elevate the levels of intracellular ROS, superoxide dismutase, hydrogen peroxide, malondialdehyde, glutathione, simultaneously reduce catalase and glutathione peroxidase levels, and upregulate HO-1, SOD-1, CAT, NQO1, GCLM mRNA levels and HO-1, SOD-1 protein levels. Additionally, Cu could observably increase the number of autophagosomes, acidic vesicle organelles (AVOs) and LC3 puncta; upregulate mRNA levels of mTOR, Beclin-1, ATG7, ATG5, ATG3, LC3II and protein levels of Beclin-1, LC3II/LC3I, downregulate LC3I mRNA level. Both treatments with BHA and ZnPP could significantly alleviate the changes of antioxidant indexes levels and ROS accumulation, reduce the increase of the number of autophagosomes, AVOs and LC3 puncta, and mitigate the above changed oxidative stress and autophagy related mRNA and protein levels induced by Cu. In summary, our findings indicated that excessive Cu could induce oxidative stress and autophagy by activating the ROS/HO-1/NQO1 pathway, and inhibition of HO-1 might attenuate Cu-induced oxidative stress and autophagy in duck renal tubular epithelial cells.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143753DOI Listing
February 2021

Endoplasmic reticulum stress aggravates copper-induced apoptosis via the PERK/ATF4/CHOP signaling pathway in duck renal tubular epithelial cells.

Environ Pollut 2021 Mar 2;272:115981. Epub 2020 Nov 2.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China. Electronic address:

Copper (Cu) is a vital micronutrient required for numerous fundamental biological processes, but excessive Cu poses potential detrimental effects on public and ecosystem health. However, the molecular details linking endoplasmic reticulum (ER) stress and apoptosis in duck renal tubular epithelial cells have not been fully elucidated. In this study, duck renal tubular epithelial cells exposed to Cu sulfate (CuSO) (0, 100 and 200 μM) and a PERK inhibitor (GSK2606414, GSK, 1 μM) for 12 h were used to investigate the crosstalk between ER stress and apoptosis under Cu exposure. Cell and ER morphological and functional characteristics, intracellular calcium (Ca) levels, apoptotic rates, ER stress and apoptosis-related mRNA and protein levels were examined. The results showed that excessive Cu could cause ER expansion and swelling, increase the expression levels of ER stress-associated genes (PERK, eIF2α, ATF4 and CHOP) and proteins (p-PERK and CHOP), induce intracellular Ca overload, upregulate the expression levels of apoptosis-associated genes (Bax, Bak1, Caspase9 and Caspase3) and the cleaved-Caspase3 protein, downregulate Bcl-xl and Bcl2 mRNA levels and trigger apoptosis. PERK inhibitor treatment could ameliorate the above changed factors caused by Cu. In conclusion, these findings indicate that excessive Cu could trigger ER stress via activation of the PERK/ATF4/CHOP signaling pathway and that ER stress might aggravate Cu-induced apoptosis in duck renal tubular epithelial cells.
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http://dx.doi.org/10.1016/j.envpol.2020.115981DOI Listing
March 2021

Cadmium and molybdenum co-exposure triggers autophagy via CYP450s/ROS pathway in duck renal tubular epithelial cells.

Sci Total Environ 2021 Mar 11;759:143570. Epub 2020 Nov 11.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, PR China. Electronic address:

Cadmium (Cd) and excessive molybdenum (Mo) are detrimental to animals, but the combined nephrotoxic impacts of Cd and Mo on duck are still unclear. To evaluate the combined impacts of Cd and Mo on autophagy via Cytochrome P450s (CYP450s)/reactive oxygen species (ROS) pathway, duck renal tubular epithelial cells were treated with 3CdSO·8HO (4.0 μM Cd), (NH)MoO·4HO (500.0 μM Mo), butylated hydroxy anisole (BHA) (100.0 μM) and combination of Cd and Mo or Cd, Mo and BHA for 12 h, and combined cytotoxicity was investigated. The results indicated that Mo or/and Cd induced CYP1A1, CYP1B1, CYP2C9, CYP3A8 and CYP4B1 mRNA levels, decreased superoxide dismutase (SOD), catalase (CAT) activities and glutathione peroxidase (GSH-Px) content, and increased malondialdehyde (MDA) and hydrogen peroxide (HO) contents. Besides, Mo or/and Cd elevated the number of autophagosome and microtubule-associated protein light chain 3 (LC3) puncta, upregulated mRNA levels of Beclin-1, LC3A, LC3B, Atg5 and adenosine 5'-monophosphate (AMP)-activated protein kinase α1 (AMPKα-1), inhibited Dynein, p62 and mammalian target of rapamycin (mTOR) mRNA levels, increased Beclin-1 and LC3II/LC3I protein levels. Moreover, the changes of these factors in Mo and Cd co-treated groups were more apparent. Additionally, BHA could efficiently alleviate the changes of above these indicators co-induced by Mo and Cd. Overall, these results manifest Cd and Mo co-exposure may synergistically trigger autophagy via CYP450s/ROS pathway in duck renal tubular epithelial cells.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143570DOI Listing
March 2021

Inhibition of ROS/NLRP3/Caspase-1 mediated pyroptosis alleviates excess molybdenum-induced apoptosis in duck renal tubular epithelial cells.

Ecotoxicol Environ Saf 2021 Jan 3;208:111528. Epub 2020 Nov 3.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address:

Objective: Excess molybdenum (Mo) is harmful to the body, and the kidney is the vital target organ for Mo exposure. This study focused on the impacts of excess Mo on pyroptosis and the relationship between pyroptosis and apoptosis in kidney.

Methods: The duck renal tubular epithelial cells were treated with (NH)MoO·4HO (0, 480, 720 and 960 μM Mo), N-acetyl-L-cysteine (NAC) (100 μM), Z-YVAD-fluoromethylketone (YVAD) (10 μM) and the combination of Mo and NAC or YVAD for 12 h. The LDH release and IL-1β, IL-18 contents of cell supernatant were detected by LDH and ELISA kits. The MMP and ROS level were measured using MMP and ROS kits by flow cytometry. The apoptotic rate of cell was detected by AO/EB counterstaining. Pyroptosis and apoptosis-related factors mRNA and protein levels were assayed by real-time qPCR and western blot, respectively.

Results: Excessive Mo markedly increased LDH, IL-18, IL-1β releases and induced overproduction of ROS, pyroptosis-related factors mRNA and protein levels. NAC and YVAD dramatically decreased pyroptosis induced by Mo. Simultaneously, YVAD significantly changed apoptosis-related factors mRNA and protein levels, and reduced cell apoptotic rate.

Conclusion: Excessive Mo exposure can induce pyroptosis by the ROS/NLRP3/Caspase-1 pathway in duck renal tubular epithelial cells, and restraining pyroptosis of Caspase-1 dependence might weaken excess Mo-induced apoptosis. The study provides theoretical basis for excess Mo exposure nephrotoxic researches on waterfowl and the interplay between pyroptosis and apoptosis highlights a new sight into the mechanism of Mo-induced nephrotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111528DOI Listing
January 2021

Smoking and Provision of Smoking Cessation Interventions among Inpatients with Acute Coronary Syndrome in China: Findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project.

Glob Heart 2020 10 23;15(1):72. Epub 2020 Oct 23.

Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, CN.

Highlights: Over half of male acute coronary syndrome patients were smokers in China.Smoking was associated with higher risk of critical cardiac symptoms at admission.Only 35.3% of smoking patients received smoking cessation interventions in China.

Background: Smoking cessation is recognized as an effective and cost-effective strategy for improving the prognosis of patients with coronary heart disease. Despite this, few studies have evaluated the smoking prevalence and provision of smoking cessation interventions among patients with acute coronary syndrome (ACS) in China.

Objectives: To evaluate the smoking prevalence, clinical conditions and in-hospital outcomes associated with smoking, and the provision of smoking cessation interventions among ACS patients in China.

Methods: This registry study was conducted using data from the Improving Care for Cardiovascular Disease in China project, a collaborative nationwide registry of the American Heart Association and the Chinese Society of Cardiology. Our study sample comprised 92,509 ACS inpatients admitted between November 2014 and December 2018. A web-based data collection platform was used to report required data.

Results: Smoking prevalence among male and female ACS patients was 52.4% and 8.0%, respectively. Patients younger than 45 years had the highest smoking rate (men: 68.0%; women: 14.9%). Compared with non-smokers, smokers had an earlier onset age of ACS and a greater proportion of severe clinical manifestations at admission, including ST-elevation myocardial infarction (67.8% versus 54.8%; p < 0.001) and substantially elevated myocardial injury markers (86.1% versus 83.0%; p < 0.001). After multivariable adjustment, smoking was associated with higher risk of critical cardiac symptoms at admission (OR = 1.14, 95% CI: 1.08-1.20; p < 0.001) and had no direct association with in-hospital outcomes (OR = 0.93, 95% CI: 0.84-1.02; p = 0.107) of ACS patients. Of 37,336 smokers with ACS, only 35.3% received smoking cessation interventions before discharge. There was wide variation in provision of smoking cessation interventions across hospitals (0%-100%).

Conclusions: Smoking is highly prevalent among ACS patients in China. However, smoking cessation interventions are not widely adopted in clinical practice in China as part of formal treatment strategies for ACS patients, indicating an important target for quality improvement.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.
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http://dx.doi.org/10.5334/gh.784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583717PMC
October 2020

Development of Megaselia spiracularis (Diptera: Phoridae) at different constant temperatures.

J Therm Biol 2020 Oct 18;93:102722. Epub 2020 Sep 18.

Department of Forensic Medicine, Soochow University, Ganjiang East Road, Suzhou, PR China. Electronic address:

Megaselia spiracularis Schmitz, 1938 (Diptera: Phoridae) is a pest that often appears in human living areas where it can spread pathogens. Besides, the species is of forensic value. Currently, studies focusing on the development of this species are limited. Understanding the developmental patterns of M. spiracularis, therefore, is important for controlling populations of this pest and for estimating the minimum postmortem interval (PMI). Here, we studied the development of M. spiracularis exposed to seven constant temperatures ranging from 16 to 34 °C. The developmental durations, accumulated degree hours and larval body length changes were measured. Three kinds of development models that can be used to estimate the PMI were established, including isomorphen diagram, isomegalen diagram and thermal summation model. The duration of M. spiracularis development at 16, 19, 22, 25, 28, 31 and 34 °C from egg to adult stage were 1131.1 ± 34.5, 807.3 ± 9.3, 529.6 ± 1.8, 367.0 ± 8.8, 302.4 ± 7.0, 250.0 ± 2.1 and 232.6 ± 1.9 h, respectively. The developmental threshold temperature and the thermal summation constant were estimated as 12.0 ± 0.5 °C and 4989.7 ± 308.9° hours, respectively. A general model represented by a logistic equation describing how larval body length will change with the time after hatching was fit to data. The present study provides basic developmental data of M. spiracularis, which can be used for achieving better control of this noxious insect as well as for estimation of its PMI at different temperatures.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102722DOI Listing
October 2020

Development of Hydrotaea spinigera (Diptera: Muscidae) at Constant Temperatures and Its Significance for Estimating Postmortem Interval.

J Med Entomol 2021 01;58(1):56-63

Department of Forensic Medicine, Soochow University, Suzhou, China.

Hydrotaea spinigera Stein is a necrophagous species, widely distributed in Oriental and Australasian regions. Considering that the postfeeding larvae or puparia of this species can still be found in abundance at the advanced decomposition stage or even the skeleton stage of remains, it can serve as a good supplementary indicator for estimating the minimum postmortem interval (PMImin). This could also extend the range of PMImin when the primary colonizers are no longer associated with the corpse or have emerged as adults. This study investigated the development duration, accumulated degree hours, and larval body length changes of H. spinigera at seven constant temperatures ranging from 16 to 34°C, and established three development models for estimating PMImin, including isomorphen diagram, isomegalen diagram, and thermal summation model. At 16, 19, 22, 25, 28, 31, and 34°C, the development durations of H. spinigera from egg to adult stage were 1,412.6 ± 62.9, 867.4 ± 14.9, 657.1 ± 22.9, 532.3 ± 10.1, 418.8 ± 21.3, 379.8 ± 16.6, and 340.0 ± 20.3 h, respectively. The lower developmental threshold L0 was estimated as 10.50 ± 0.20°C, and the thermal summation constant K was 7,648.83 ± 146.74 degree hours. Using regression analysis, equations were obtained modeling the change of larval body length with time after hatching at different temperatures. This study provided basic data based on the growth and development of H. spinigera for the estimation of PMImin in forensic science.
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http://dx.doi.org/10.1093/jme/tjaa162DOI Listing
January 2021

Inhibition of autophagy enhances cadmium-induced apoptosis in duck renal tubular epithelial cells.

Ecotoxicol Environ Saf 2020 Dec 21;205:111188. Epub 2020 Aug 21.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China. Electronic address:

Increasing evidence indicates autophagy and apoptosis are involved in the toxicity mechanism of heavy metals. Our previous studies showed that cadmium (Cd) could induce autophagy and apoptosis in duck kidneys in vivo, nevertheless, the interaction between them has yet to be elucidated. Herein, the cells were either treated with 3CdSO·8HO (0, 1.25, 2.5, 5.0 μM Cd) or/and 3-methyladenine (3-MA) (2.5 μM) for 12 h and the indictors related autophagy and apoptosis were detected to assess the correlation between autophagy and apoptosis induced by Cd in duck renal tubular epithelial cells. The results demonstrated that Cd exposure notably elevated intracellular and extracellular Cd contents, the number of autophagosomes and LC3 puncta, up-regulated LC3A, LC3B, Beclin-1, Atg5 mRNA levels, and Beclin-1 and LC3II/LC3I protein levels, down-regulated mTOR, p62 and Dynein mRNA levels and p62 protein level. Additionally, autophagy inhibitor 3-MA decreased Beclin-1, LC3II/LC3I protein levels and increased p62 protein level. Moreover, co-treatment with Cd and 3-MA could notably elevate Caspase-3, Cyt C, Bax, and Bak-1 mRNA levels, Caspase-3 and cleaved Caspase-3 protein levels, and cell apoptotic rate as well as cell damage, decreased mitochondrial membrane potential (MMP), Bcl-2 mRNA level and the ratio of Bcl-2 to Bax compared to treatment with Cd alone. Overall, these results indicate Cd exposure can induce autophagy in duck renal tubular epithelial cells, and inhibition of autophagy might aggravate Cd-induced apoptosis through mitochondria-mediated pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111188DOI Listing
December 2020

Exposed to Mercury-Induced Oxidative Stress, Changes of Intestinal Microflora, and Association between them in Mice.

Biol Trace Elem Res 2021 May 30;199(5):1900-1907. Epub 2020 Jul 30.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China.

Twelve Kunming mice were randomly divided into two groups (n = 6), and administered with distilled water containing 0 mg/L and 160 mg/L HgCl respectively, with an experimental period of 3 days. Our results showed that mercury exposure significantly reduced weight gain in mice (P < 0.01). Through pathological observation of cecum tissues, significant pathological changes were observed in cecum tissues of mice exposed to mercury. Furthermore, mercury exposure not only significantly increased malondialdehyde (MDA) content in mice (P < 0.01) but also significantly decreased superoxide dismutase (SOD) activity (P < 0.01) and glutathione peroxidase (GSH) level in mice (P < 0.01). Furthermore, high-throughput sequencing analysis showed that at the genus level some microbial populations including Clostridiales, Lactobacillus, Treponema, Oscillospira, and Desulfovibrio were significantly increased whereas some microbial populations including S24-7, Acinetobacter, and Staphylococcus were significantly decreased. Moreover, correlation analysis indicated that microorganisms were not correlated with biomarkers of oxidative stress. In summary, mercury exposure reduced the growth performance of mice, resulting in gut microbiota alterations, and led to oxidative stress by increasing the concentration of malondialdehyde (MDA) and decreasing the concentration of superoxide dismutase (SOD) and glutathione peroxidase (GSH).
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http://dx.doi.org/10.1007/s12011-020-02300-xDOI Listing
May 2021

Secretion of human soluble programmed cell death protein 1 by chimeric antigen receptor-modified T cells enhances anti-tumor efficacy.

Cytotherapy 2020 12 17;22(12):734-743. Epub 2020 Jul 17.

Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China; Department of Hematopoietic Stem Cell Transplantation, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Hematopoietic Stem Cell Transplantation, the Cell and Gene Therapy Center, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Beijing Key Laboratory of Stem Cell Therapy and Transformation Research, Beijing, China. Electronic address:

Background Aims: Chimeric antigen receptor (CAR) T cells have achieved favorable responses in patients with hematologic malignancies, but the outcome has been far from satisfactory in the treatment of tumors with high expression of immunosuppressive molecules. To overcome this limitation, we modified CAR T cells to secrete types of human soluble programmed cell death protein 1 (PD-1) called sPD-1 CAR T cells.

Methods: To compare the effector function between second (conventional second-generation CAR targeting CD19) and sPD-1 CAR T cells, we measured cytotoxicity, cytokine secretion and activation markers incubated with or without tumor cells expressing CD19 and/or programmed cell death ligand 1 (PD-L1). Furthermore, the anti-tumor efficacy of second and sPD-1 CAR T cells was determined using an NSG mouse model bearing NALM-6-PD-L1. Finally, the underlying mechanism was investigated by metabolic parameters and RNA sequencing analysis of different CAR T cells.

Results: Compared with second CAR T cells, sPD-1 CAR T cells enhanced killing efficiency toward CD19PD-L1 tumor cells in vitro. Furthermore, sPD-1 CAR T cells reduced the tumor burden and prolonged overall survival of the NSG (NOD-SCID-IL2rg) mice bearing NALM-6-PD-L1. To explore the effect of soluble PD-1 on CAR T cells, we found that sPD-1 CAR T cells exhibited higher levels of activation and ameliorative profiles of differentiation, exhaustion, glycolysis and apoptosis.

Conclusions: With constitutive soluble PD-1 secretion, sPD-1 CAR T cells have tended to eradicate tumors with a high expression of PD-L1 more effectively than second CAR T cells. This may be due to soluble PD-1 enhancing apoptosis resistance, aerobic metabolism and a more "stem" differentiation of CAR T cells. Overall, our study presents a feasible strategy to increase the efficacy of CAR T cells.
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http://dx.doi.org/10.1016/j.jcyt.2020.05.007DOI Listing
December 2020

Development of Necrobia rufipes (De Geer, 1775) (Coleoptera: Cleridae) under constant temperatures and its implication in forensic entomology.

Forensic Sci Int 2020 Jun 1;311:110275. Epub 2020 Apr 1.

Department of Forensic Medicine, Soochow University, Ganjiang East Road, Suzhou, China. Electronic address:

After the death of humans or animals, the odors released at different stages of decay attract various insects, and other arthropods, to the corpses. Therefore, the development of insects, and other arthropods present on corpses, can be assessed to estimate the minimum postmortem interval since death. In general, necrophagous blow flies are the insects that first colonize corpses. With progressing decay, other necrophagous and predatory insects arrive at the corpses, which will develop on or around these either by feeding directly on the corpses or by prey on other immature insects. Beetles (Coleoptera) mainly arrive at the corpses during the later stages of decay, and play important roles in cases with longer postmortem intervals. Necrobia rufipes (De Geer, 1755) (Coleoptera: Cleridae) is an important stored-product species with world-wide distribution. Moreover, it is also a forensically important insect species. At temperatures of 22, 25, 28, 31, 34, and 36°C (±0.5°C), the developmental periods from egg to adult were 113.20±2.96, 66.16±3.22, 50.61±1.95, 38.26±2.48, 37.97±2.40, and 31.20±2.11 days, respectively. In vivo measurements obtained the morphological indexes of larvae. The growth curve and the equation of the relationship between development time, body lengths, and mesonotum widths were simulated. The isomorphen diagram model, the isomegalen diagram model, and the thermal summation model were established. In addition, the widths of head capsules and pronota of larvae at different instars were determined by cluster analysis. Classifiers were created and validated by linear discriminant analysis.
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http://dx.doi.org/10.1016/j.forsciint.2020.110275DOI Listing
June 2020

Temperature-dependent development of Omosita colon at constant temperature and its implication for PMI estimation.

J Forensic Leg Med 2020 May 28;72:101946. Epub 2020 Mar 28.

Department of Forensic Medicine, Soochow University, Ganjiang East Road, Suzhou, China. Electronic address:

Omosita colon (Linnaeus, 1758) (Coleoptera: Nitidulidae) is a species widely distributed in the Holarctic that usually appears during more advanced stages of decay. It is one of the species found on highly decomposed remains. Although O. colon may be a promising indicator of post-mortem interval (PMI) in cases with longer PMI, there is currently no existing research on its growth and development. Therefore, we studied the development of O. colon at seven constant temperatures between 16 and 34 °C and found that O. colon can complete its entire life cycle between 16 and 31 °C, but failed to complete development at 34 °C. At 16, 19, 22, 25, 28, and 31 °C, the developmental duration of O. colon from egg to adult is 95.3 ± 11.4, 62.4 ± 8.5, 45.9 ± 2.8, 34.9 ± 3.4, 30.0 ± 2.6, and 25.2 ± 2.6 d, respectively. Based on the results of development time and accumulated degree days, an isomorphen diagram was plotted and a thermal summation model was established. The mean (±SE) developmental threshold temperature D and the thermal summation constant K calculated using the thermal summation model were 10.65 ± 0.16 °C and 514.1 ± 8.7° days, respectively. The results of this study provide fundamental developmental data for the use of O. colon in minimum post-mortem interval (PMI) estimations.
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http://dx.doi.org/10.1016/j.jflm.2020.101946DOI Listing
May 2020

Development of Lucilia sericata (Diptera: Calliphoridae) Under Constant Temperatures and its Significance for the Estimation of Time of Death.

J Med Entomol 2020 09;57(5):1373-1381

Department of Forensic Medicine, Soochow University, Suzhou, China.

Forensic entomologists usually estimate the minimum postmortem interval (PMImin) using the time required for the oldest immature insects found on the corpse to grow to its development stage and age at the time of discovery. The sheep blow fly Lucilia sericata (Meigen, 1826) is a carrion fly found nearly worldwide, and important in forensics. We studied the development time of L. sericata from egg to adult at constant temperatures of 16, 19, 22, 25, 28, 31, and 34°C, and found that the times required are 913.2 ± 19.4, 588.8 ± 35.8, 459.8 ± 15.2, 373.2 ± 15.3, 308.0 ± 9.7, 272.5 ± 9.2, and 267.5 ± 10.5 h, respectively. We established three development models to infer the age of the immature insect: isomegalen diagram, isomorphen diagram, and thermal summation model. In addition, a regression analysis was performed on the relationship between body length and total development time from hatching to dispersing. The thermal summation constant during the development of L. sericata is 6023.2 degree hours and development threshold temperature is 9.19°C. The results of this experiment provide a basis for the use of L. sericata in the estimation of PMImin.
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http://dx.doi.org/10.1093/jme/tjaa046DOI Listing
September 2020

Subchronic oral mercury caused intestinal injury and changed gut microbiota in mice.

Sci Total Environ 2020 Jun 29;721:137639. Epub 2020 Feb 29.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Mercury is a key global pollutant, yet the mechanism by which mercury-exposure causes intestinal injury is not clear, we aimed to investigate the mechanism of intestinal injury and gut microbiota changes caused by mercury-exposure. Twelve Kunming mice were divided into two groups (n = 6), and the two groups were treated with 0 mg/L and 80 mg/L HgCl in drinking water for 90 days respectively. Our results showed that mercury-exposure prominently effected body weight gain and glucose levels. The mercury-exposed mice showed intestinal injury, which was diagnosed by Histopathological Examination and Transmission Electron Microscopy. Meanwhile, RT-PCR indicated that mercury-exposure significantly increased the expression of pro-apoptotic genes including Bax, JNK, ASK1, caspase3 and TNF-α, and significantly decreased the expression of the anti-apoptotic gene Bcl-2. Furthermore, high-throughput sequencing analysis showed that at the genus level some microbial populations including Coprococcus, Oscillospira and Helicobacter were significantly increased whereas some microbial populations including Lgnatzschineria, Salinicoccus and Bacillus were significantly decreased. Moreover, PICRUSt analysis revealed potential metabolic changes. Correlation analysis indicated that microorganisms were significantly correlated with apoptotic gene expression. In summary, our results indicated that mercury-exposure affected the growth and development of mice, induced intestinal microbiota dysbiosis and metabolic disorder, and aggravated apoptosis in mice.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137639DOI Listing
June 2020

Investigation of the effects of dichlorvos poisoning on AMPK signaling pathway in chicken brain tissues.

Environ Pollut 2020 Jun 12;261:114109. Epub 2020 Feb 12.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Dichlorvos is a common crop insecticide widely used by people which causes extensive and serious environmental pollution. However, it has been shown that organophosphorus poisoning causes energy metabolism and neural disorders. The overall purpose of this study was to investigate the damage to brain tissue and the changes in AMPK signaling pathway-related gene expression after dichlorvos poisoning in chickens. White-feathered broiler chickens, as the research subjects of this experiment, were divided into three groups: control group, low-dose group (77.5% dichlorvos at 1.13 mg/kg dose) and high-dose group (77.5% dichlorvos at 10.2 mg/kg dose). Clinical symptoms were observed after modeling, and an integrative analysis was conducted using HE staining microscopy, immune-histochemical microscopy, electron microscopy and PCR arrays. The results showed that the high-dose group had more obvious dyspnea, salivation, convulsion and other neurological phenomena. Pathological sections showed that nuclear disintegration of neurons was most obvious in the low-dose group, and apoptosis of brain cells was most obvious in the high-dose group, and the mitochondrial structure was destroyed in the two poisoned group, i.e. low-dose group and high-dose group. PCR arrays showed that AMPK signaling pathway was inhibited and the expressions of genes involved in energy metabolism (ACACA and PRKAA1) were significantly changed. Furthermore, genes associated with protein synthesis (EIF4EBP1) were significantly upregulated. FASN and HMGCR expressions were significantly increased. There were significant changes in the expressions of cell cycle-related genes (STK11, TP53 and FOXO3). Organophosphate poisoning can cause a lot of nuclear disintegration of brain neurons, increases cell apoptosis, disrupts the energy metabolism of mitochondrial structure, and inhibits the AMPK signaling pathway. These results provide a certain idea and basis for studying the mechanism of AMPK signaling after organophosphorus poisoning and provide a research basis for the prevention and treatment of organophosphorus poisoning.
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http://dx.doi.org/10.1016/j.envpol.2020.114109DOI Listing
June 2020

16S rRNA gene sequencing reveals an altered composition of the gut microbiota in chickens infected with a nephropathogenic infectious bronchitis virus.

Sci Rep 2020 02 26;10(1):3556. Epub 2020 Feb 26.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China.

Infectious bronchitis virus (IBV), a member of the Coronaviridae family, causes serious losses to the poultry industry. Intestinal microbiota play an important role in chicken health and contribute to the defence against colonization by invading pathogens. The aim of this study was to investigate the link between the intestinal microbiome and nephropathogenic IBV (NIBV) infection. Initially, chickens were randomly distributed into 2 groups: the normal group (INC) and the infected group (IIBV). The ilea were collected for morphological assessment, and the ileal contents were collected for 16S rRNA gene sequencing analysis. The results of the IIBV group analyses showed a significant decrease in the ratio of villus height to crypt depth (P < 0.05), while the goblet cells increased compared to those in the INC group. Furthermore, the microbial diversity in the ilea decreased and overrepresentation of Enterobacteriaceae and underrepresentation of Chloroplast and Clostridia was found in the NIBV-infected chickens. In conclusion, these results showed that the significant separation of the two groups and the characterization of the gut microbiome profiles of the chickens with NIBV infection may provide valuable information and promising biomarkers for the diagnosis of this disease.
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http://dx.doi.org/10.1038/s41598-020-60564-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044311PMC
February 2020

The protective effects of resveratrol on antioxidant function and the mRNA expression of inflammatory cytokines in the ovaries of hens with fatty liver hemorrhagic syndrome.

Poult Sci 2020 Feb 20;99(2):1019-1027. Epub 2019 Dec 20.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, P. R. China. Electronic address:

To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of resveratrol (RSV) against FLHS in laying hens, 144 healthy 90-day-old laying hens were randomly divided into 4 groups including control (Con) group, high-energy low-protein (HELP) group, RSV group, and HELP + RSV group, each of which contained 36 hens with 3 replicates. Birds in the 4 groups were fed a basal diet, HELP diet, basal diet supplemented with 400 mg/kg RSV, and HELP diet supplemented with 400 mg/kg RSV. The histopathology of the ovary lesions on day 120, egg production, antioxidative function, and mRNA expression levels of inflammatory cytokines on days 40, 80, and 120 were determined. The lipid accumulation and hemorrhaging were more severe in the HELP group than those in the HELP + RSV group. The laying rate was markedly decreased in the HELP group compared with that in the Con and HELP + RSV groups. Furthermore, the malondialdehyde concentration was significantly increased (P < 0.05), while the levels of superoxide dismutase (SOD), catalase, and glutathione were significantly decreased (P < 0.05) in the HELP group compared with those in the Con and HELP + RSV groups. The mRNA levels of antioxidant genes (Nrf2, SOD-1, and HO-1) were markedly increased (P < 0.05) in the HELP + RSV group compared with those in the HELP group. In addition, the mRNA levels of inflammation-related genes (nuclear factor kappa B, tumor necrosis factor-α, IL-1β, and IL-6) were significantly increased (P < 0.05) in the HELP group compared with those in the Con and HELP + RSV groups. Collectively, these results indicate that oxidative stress and inflammation are involved in the occurrence and development of FLHS in the ovaries of laying hens, but RSV effectively attenuates oxidative stress and inflammation in hens with FLHS. Hence, RSV can be used as an effective feed additive to protect against FLHS.
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http://dx.doi.org/10.1016/j.psj.2019.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587695PMC
February 2020

Molybdenum Induces Mitochondrial Oxidative Damage in Kidney of Goats.

Biol Trace Elem Res 2020 Sep 7;197(1):167-174. Epub 2019 Dec 7.

College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, P. R. China.

The purpose of this study was to evaluate the effects of excessive molybdenum (Mo) on renal function and oxidative stress in goats. Twenty-seven healthy goats were randomly allotted in three groups and were fed deionized water to which sodium molybdate [(NH)MoO·4HO] was added at different doses of 0, 15, and 45 mg Mo/(kg·BW) for 50 days, respectively. The results indicated that white blood cell (WBC) counts were significantly increased (P < 0.05), while red blood cell (RBC) counts, hemoglobin (HGB), and mean corpuscular hemoglobin concentration (MCH) were tended to decrease with the increasing of the experimental period in high-Mo group compared with the control group. Besides, blood urea nitrogen (BUN) and creatinine (CREA) contents in serum were increased (P < 0.05) in both groups supplemented with molybdenum. Meanwhile, contents of copper (Cu) from the both experimental groups were significantly decreased (P < 0.05), while contents of zinc (Zn) and iron (Fe) were increased (P < 0.05) in serum. The contents of Cu were significantly increased (P < 0.05), while the contents of zinc (Zn) and iron (Fe) did not obviously change (P > 0.05) in the kidney. In addition, the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased (P < 0.05) in the mitochondria, whereas malondialdehyde (MDA) and nitric oxide synthase (NOS) expression significantly increased (P < 0.05). Collectively, these results indicated that excess Mo exposure could induce secondary Cu deficiency and oxidative stress in the kidney, which finally undermine the renal function of goats.
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http://dx.doi.org/10.1007/s12011-019-01991-1DOI Listing
September 2020

Abnormal expression of liver autophagy and apoptosis-related mRNA in fatty liver haemorrhagic syndrome and improvement function of resveratrol in laying hens.

Avian Pathol 2020 Apr 7;49(2):171-178. Epub 2020 Jan 7.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, People's Republic of China.

Fatty liver haemorrhagic syndrome (FLHS) is characterized by hepatic rupture and haemorrhage leading to sudden death in laying hens. Resveratrol (Res) is a natural polyphenol with antioxidant and anti-inflammatory effects that can ameliorate chronic liver disease. The aim of this study was to investigate the improved effect of Res on the altered expression of autophagy and apoptosis-related genes in laying hens with FLHS. A total of 144 healthy 150-day-old laying hens were randomly divided into four groups: control group (standard diet), HELP group (high-energy-low-protein (HELP) diet), HELP + Res group (HELP diet with 400 mg/kg Res) and Res group (standard diet with 400 mg/kg Res). Histopathological lesions of the liver and the mRNA levels of Beclin-1, Atg5, Atg7, p62, Bcl-2, Bax and Caspase-3 on days 40, 80, and 120 were measured. The results showed that lipid accumulation and hepatocyte damage in the HELP group were more serious than those in the HELP + Res group. The mRNA levels of Beclin-1, Atg5, Atg7, and Bcl-2 in the HELP and HELP + Res groups were strikingly declined (< 0.01) compared to the control group, and their mRNA levels were markedly higher in HELP group than those in the HELP + Res group (< 0.05). Additionally, the mRNA levels of p62, Bax and Caspase-3 were significantly increased in the HELP and HELP + Res groups (< 0.01 or < 0.05), but their mRNA levels in the HELP group were higher than those in the HELP + Res group (< 0.05). Collectively, FLHS could induce severe lipid accumulation, abnormal mRNA levels of liver autophagy and apoptosis-related genes. Res as a dietary supplement could attenuate these abnormal changes.
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http://dx.doi.org/10.1080/03079457.2019.1698712DOI Listing
April 2020