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1.
J Cardiovasc Pharmacol ; 83(2): 193-204, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38030139

ABSTRACT

ABSTRACT: Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice. On day 14 after surgery, echocardiography showed that left ventricle mass (LV mass), interventricular septum, left ventricle posterior wall diastole, and left ventricular posterior wall systole were significantly increased, and ejection fraction was decreased compared with control mice. Masson and Wheat Germ Agglutinin staining indicated enhanced myocardial fibrosis and cell morphology compared with control mice. Importantly, these effects were inhibited by DAPA treatment in ISO-induced mice. In H9c2 cells and neonatal rat cardiomyocytes, we found that mitochondrial fragmentation and mitochondrial oxidative stress were significantly augmented in the ISO-induced group. However, DAPA rescued the cardiac hypertrophy in ISO-induced H9c2 cells and neonatal rat cardiomyocytes. Mechanistically, we found that DAPA restored the PIM1 activity in ISO-induced H9c2 cells and subsequent increase in dynamin-associated protein 1 (Drp1) phosphorylation at S616 and decrease in Drp1 phosphorylation at S637 in ISO-induced cells. We found that DAPA mitigated ISO-induced cardiac hypertrophy by suppressing Drp1-mediated mitochondrial fission in a PIM1-dependent fashion.


Subject(s)
Benzhydryl Compounds , Cardiomegaly , Glucosides , Mitochondrial Dynamics , Rats , Mice , Male , Animals , Isoproterenol/pharmacology , Mice, Inbred C57BL , Cardiomegaly/metabolism , Myocytes, Cardiac
3.
Natl Sci Rev ; 10(3): nwac272, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36875785

ABSTRACT

Simultaneously achieving high electrochemical activity and high loading for solid-state batteries has been hindered by slow ion transport within solid electrodes, in particular with an increase in electrode thickness. Ion transport governed by 'point-to-point' diffusion inside a solid-state electrode is challenging, but still remains elusive. Herein, synchronized electrochemical analysis using X-ray tomography and ptychography reveals new insights into the nature of slow ion transport in solid-state electrodes. Thickness-dependent delithiation kinetics are spatially probed to identify that low-delithiation kinetics originate from the high tortuous and slow longitudinal transport pathways. By fabricating a tortuosity-gradient electrode to create an effective ion-percolation network, the tortuosity-gradient electrode architecture promotes fast charge transport, migrates the heterogeneous solid-state reaction, enhances electrochemical activity and extends cycle life in thick solid-state electrodes. These findings establish effective transport pathways as key design principles for realizing the promise of solid-state high-loading cathodes.

4.
J Cardiovasc Pharmacol ; 79(6): 925-934, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35234738

ABSTRACT

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.


Subject(s)
Hydrogen Sulfide , Mitochondrial Dynamics , Cells, Cultured , Fibroblasts/metabolism , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology
5.
Fish Shellfish Immunol ; 55: 516-22, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27343373

ABSTRACT

To reduce the economic losses caused by diseases in aquaculture industry, more efficient and economic prophylactic measures should be urgently investigated. In this research, the effects of a novel functionalized single-walled carbon nanotubes (SWCNTs) applied as a delivery vehicle for DNA vaccine administration in juvenile grass carp against Aeromonas hydrophila were studied. Our results showed that SWCNTs loaded with DNA vaccine induced a better protection to juvenile grass carp against A. hydrophila. Moreover, SWCNTs conjugated with DNA vaccine provided significantly protective immunity compared with free DNA vaccine. Thereby, SWCNTs may be considered as a potential efficient DNA vaccine carrier to enhance the immunological activity.


Subject(s)
Aeromonas hydrophila/immunology , Bacterial Vaccines/immunology , Carps , Fish Diseases/immunology , Gram-Negative Bacterial Infections/veterinary , Nanotubes, Carbon , Animals , Fish Diseases/microbiology , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/microbiology , Immunity, Innate , Random Allocation , Vaccines, DNA/immunology
6.
Org Biomol Chem ; 13(29): 7993-8000, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26111901

ABSTRACT

A chiral phosphoric acid-catalyzed asymmetric reaction of 2-indolylmethanols with 3-alkylindoles has been established, which constructed a biologically important 2,2'-bisindolylmethane scaffold in high yields and good enantioselectivities (up to 98% yield, 94:6 er). This protocol not only provides an efficient method for constructing a 2,2'-bisindolylmethane framework in an enantioselective form, but also promotes the development of 2-indolylmethanol-involved catalytic asymmetric transformations.


Subject(s)
Indoles/chemistry , Methane/chemistry , Methanol/chemistry , Catalysis , Crystallography, X-Ray , Solvents/chemistry , Stereoisomerism
7.
Fish Shellfish Immunol ; 45(1): 175-83, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25862971

ABSTRACT

Intestinal microbiota has become an integral component of the fish, and plays a key role in host metabolism, immunity and health maintenance. However, information on the immune responses after vaccine administration in relation to the intestinal microbiota is absent in fish. The present study focused on the effect of a new recombinant Aeromonas hydrophila vaccine (Aera) by using a novel functionalized, single-walled carbon nanotubes (SWCNTs) as a delivery vehicle on the intestinal microbiota of grass carp (Ctenopharyngodon idella) through the bath immunization, and further explored the immunological responses in intestine, kidney and spleen. By performing deep sequencing, a total of 81,979 valid reads and 609 OTUs obtained from 4 intestine samples were analyzed. We detected 141 genuses, most of which belonged to Firmicutes, Fusobacteria and Proteobacteria. Of note, the quantity of Aeromonas in library Aera (after 6 h Aera vaccine pretreatment, fish were transferred to tanks without SWCNTs-Aera for 28 d) and Aera-GD (6 h Aera vaccine pretreated prior to the group injected by A. hydrophila) was declined 6.5% and 14.6% compared with the control, respectively. Moreover, the expression of seven immune-related genes (IFN-I, TNF-α, CRP, IL-8, IgM, MHC I and CD8α) in the intestine, kidney and spleen of Aera treated fish was significantly enhanced, which indicated that a better tissue immune response in grass carp was induced by the SWCNTs-Aera vaccine. Therefore, a new recombinant SWCNT-Aera vaccine may represent potentially efficient and immunological role in grass carp intestine to resist A. hydrophila infection.


Subject(s)
Aeromonas hydrophila/immunology , Bacterial Vaccines/immunology , Carps , Fish Diseases/prevention & control , Gastrointestinal Microbiome , Gram-Negative Bacterial Infections/veterinary , Immunity, Innate , Animals , DNA, Bacterial/genetics , DNA, Bacterial/metabolism , Fish Diseases/microbiology , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/prevention & control , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Vaccines, Synthetic/immunology
8.
Ecotoxicol Environ Saf ; 116: 68-75, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25768424

ABSTRACT

Due to the high chemical and photochemical stability, an organophosphorus pesticide triazophos might enter aquatic ecosystems and impose negative effect on aquatic organisms. In order to investigate short-term toxicity of triazophos on goldfish (Carassius auratus), antioxidant response in brain, spleen, kidney and liver was tested in this study. As a confirmation, the impact of triazophos on acetyl cholinesterase (AChE) activity was found a reduction in all studied tissues, especially in brain. In addition, 0.1 and 0.5 mg L(-1) triazophos induced MDA level increased, while glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) activities decreased. Of note, more prominent oxidative stress was provoked in kidney and liver, but weaker in brain and spleen. These results revealed that triazophos could cause a generalized oxidative stress and tissue specific antioxidant response in goldfish. Furthermore, neuroendocrine-growth-related gene expression (growth hormone (GH), luteinizing hormone (LH) and peptide YY) in brain was also changed by exposed to triazophos during 4 and 7d exposure periods. Linked with the above results, the present study pointed out that triazophos might induce a neurotoxic effect and oxidative damage in goldfish, and the goldfish brain should be a critical target for triazophos-induced damage.


Subject(s)
Antioxidants/metabolism , Organothiophosphates/toxicity , Pesticides/toxicity , Triazoles/toxicity , Water Pollutants, Chemical/toxicity , Animals , Brain/drug effects , Brain/enzymology , Catalase/metabolism , Gene Expression/drug effects , Glutathione/metabolism , Goldfish/genetics , Goldfish/metabolism , L-Lactate Dehydrogenase/metabolism , Organ Specificity , Oxidative Stress , Superoxide Dismutase/metabolism
9.
J Org Chem ; 80(3): 1841-8, 2015 Feb 06.
Article in English | MEDLINE | ID: mdl-25561356

ABSTRACT

A catalyst-controlled chemoselective formal 1,2-addition of 3-indolylmethanols with cyclic enaminones has been established in the presence of TfOH as a strong acid, which afforded C2-functionalized indole derivatives in generally good yields (up to 89% yield). This reaction not only confronted the great challenge in 1,2-addition of 3-indolylmethanols but also provided a good strategy for C2-functionalization of indole derivatives. The investigation on the reaction mechanism revealed that this formal 1,2-addition included a tandem sequence of 1,4-addition/[1,3]-C migration/isomerization, in which the [1,3]-C migration of the 1,4-addition product was a key step and the acidity of the catalyst played a decisive role in the observed chemoselectivity.


Subject(s)
Indoles/chemistry , Catalysis , Cyclization , Molecular Structure
10.
Fish Shellfish Immunol ; 42(1): 213-20, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25462556

ABSTRACT

To reduce the economic losses caused by diseases in aquaculture industry, more efficient and economic prophylactic measures should be urgently investigated. In this research, the effects of a novel functionalized single-walled carbon nanotubes (SWCNTs) applied as a delivery vehicle for recombinant Aeromonas hydrophila vaccine administration via bath or injection in juvenile grass carp were studied. The results showed that SWCNT as a vector for the recombinant protein aerA, augmented the production of specific antibodies, apparently stimulated the induction of immune-related genes, and induced higher level of survival rate compared with free aerA subunit vaccine. Furthermore, we compared the routes of bath and intramuscular injection immunization by SWCNTs-aerA vaccine, and found that similar antibody levels induced by SWCNTs-aerA were observed in both immunization routes. Meanwhile, a similar relative percentage survival (approximately 80%) was found in both a 40 mg/L bath immunization group, and a 20 µg injection group. The results indicate that functionalized SWCNTs could be a promising delivery vehicle to potentiate the immune response of recombinant vaccines, and might be used to vaccinate juvenile fish by bath administration method.


Subject(s)
Aeromonas hydrophila/immunology , Bacterial Vaccines/pharmacology , Carps , Fish Diseases/microbiology , Fish Diseases/prevention & control , Gram-Negative Bacterial Infections/veterinary , Nanotubes, Carbon , Analysis of Variance , Animals , Antibodies, Bacterial/immunology , Bacterial Vaccines/administration & dosage , DNA Primers/genetics , Drug Delivery Systems/methods , Drug Delivery Systems/veterinary , Enzyme-Linked Immunosorbent Assay , Gram-Negative Bacterial Infections/prevention & control , Real-Time Polymerase Chain Reaction , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/pharmacology
11.
Fish Shellfish Immunol ; 42(2): 325-34, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25463298

ABSTRACT

The uses of single walled carbon nanotubes (SWCNTs) as carriers for DNA delivery have received considerable attention in cell studies. DNA vaccination of fish has been shown to elicit durable transgene expression, but no reports exist on intramuscular administration of SWCNTs-DNA vaccine electrostatic complexes which prepared through non-covalent conjugation. In this study, we injected grass carp intramuscularly with a plasmid vector containing a major capsid protein gene (vp7) of grass carp reovirus as a) naked pcDNA-vp7, b) SWCNTs-pcDNA-vp7, c) empty plasmid vector, or phosphate buffered saline. After intramuscular administration, the ability of the different immune treatments to induce transgene expression was analyzed. The results indicated that higher levels of transcription and expression of the vp7 gene could be detected in muscle tissues of grass carp 28 days intramuscular injection in SWCNTs-pcDNA-vp7 treatment groups compare with naked pcDNA-vp7 treatment groups. Moreover, the serum respiratory burst activity, complement activity, lysozyme activity, superoxide dismutase activity, immune-related genes, antibody levels and relative percentage survival were significantly enhanced in fish immunized with SWCNTs-pcDNA-vp7 vaccine. The data in this study suggested that SWCNTs were promising carriers for plasmid DNA vaccine and might be used to vaccinate fish by intramuscular approach.


Subject(s)
Capsid Proteins/immunology , Carps , Fish Diseases/immunology , Nanotubes, Carbon/analysis , Reoviridae Infections/veterinary , Reoviridae/immunology , Viral Vaccines/immunology , Animals , Capsid Proteins/genetics , Immunity, Innate , Immunization/veterinary , Reoviridae/genetics , Reoviridae Infections/immunology , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Viral Vaccines/genetics
12.
Chem Commun (Camb) ; 50(100): 15901-4, 2014 Dec 28.
Article in English | MEDLINE | ID: mdl-25380514

ABSTRACT

An organocatalytic asymmetric formal [3+2] cycloaddition of isatin-derived 3-indolylmethanol with 3-methyl-2-vinylindole has been established, leading to highly stereoselective construction of a spiro[cyclopenta[b]indole-1,3'-oxindole] scaffold with the concomitant creation of three contiguous stereogenic centers (72-99% yield, all >95 : 5 dr, 90-98% ee), one of which is an all-carbon quaternary stereogenic center.


Subject(s)
Indoles/chemistry , Spiro Compounds/chemistry , Catalysis , Cycloaddition Reaction , Indoles/chemical synthesis , Stereoisomerism
13.
Fish Shellfish Immunol ; 41(2): 279-93, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25240976

ABSTRACT

Grass carp reovirus (GCRV), the most pathogenic aquareovirus, can cause fatal hemorrhagic disease in fingerling and yearling grass carp. Vaccination by injection is by far the most effective method of combating disease. However it is labor intensive, costly and not feasible to vaccinate large numbers of the fish. Thus, an efficient and economic strategy for the prevention of GCRV infection becomes urgent. Here, functionalized single-walled carbon nanotubes (SWCNTs) as carrier were used to manufacture SWCNTs-VP7 subunit vaccine with chemical modification. Different developmental stages of grass carps were immunized by VP7/SWCNTs-VP7 subunit vaccine against GCRV by intramuscular injection and bath immunization. The results indicate that better immune responses of grass carp immunized with the SWCNTs-VP7 subunit vaccine were induced in comparison with VP7 subunit vaccine alone. Immunization doses/concentrations are significantly reduced (about 5-8 times) to prevent GCRV infection in different developmental stages of grass carp with injection or bath treatment when SWCNTs carrier was used. A good immune protective effect (relative percentage survival greater than 95%) is observed in smaller size fish (0.2 g) with SWCNTs-VP7 bath immunization. In addition, serum respiratory burst activity, complement activity, lysozyme activity, superoxide dismutase activity, alkaline phosphatase activity, immune-related genes and antibody levels were significantly enhanced in fish immunized with vaccine. This study suggested that functionalized SWCNTs was the promising carrier for recombinant subunit vaccine and might be used to vaccinate fish by bath approach.


Subject(s)
Carps , Drug Delivery Systems/methods , Fish Diseases/prevention & control , Fish Diseases/virology , Nanotubes, Carbon , Reoviridae Infections/veterinary , Reoviridae/immunology , Viral Vaccines/therapeutic use , Alkaline Phosphatase/blood , Animals , Antibodies, Viral/blood , Aquaculture/methods , China , Cloning, Molecular , Complement System Proteins/immunology , DNA Primers/genetics , Immunization/methods , Muramidase/metabolism , Real-Time Polymerase Chain Reaction , Reoviridae Infections/prevention & control , Respiratory Burst/immunology , Reverse Transcriptase Polymerase Chain Reaction , Superoxide Dismutase/blood
14.
Environ Sci Pollut Res Int ; 21(23): 13625-35, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25028328

ABSTRACT

Using rare minnow (Gobiocypris rarus) at early-life stages as experimental models, the developmental toxicity of five widely used triazole fungicides (myclobutanil, fluconazole, flusilazole, triflumizole, and epoxiconazole) were investigated following exposure to 1-15 mg/L for 72 h. Meanwhile, morphological parameters (body length, body weight, and heart rate), enzyme activities (superoxide dismutase (SOD), glutathione S-transferase (GST), adenosine triphosphatase (ATPase), and acetyl cholinesterase (AChE)), and mRNA levels (hsp70, mstn, mt, apaf1, vezf1, and cyp1a) were also recorded following exposure to 0.2, 1.0, and 5.0 mg/L for 72 h. Results indicated that increased malformation and mortality, decreased body length, body weight, and heart rate provide a concentration-dependent pattern; values of 72 h LC50 (median lethal concentration) and EC50 (median effective concentration) ranged from 3 to 12 mg/L. Most importantly, the results of the present study suggest that even at the lowest concentration, 0.2 mg/L, five triazole fungicides also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that those five triazole fungicides are highly toxic to the early development of G. rarus embryos. The information presented in this study will be helpful in better understanding the toxicity induced by triazole fungicides in fish embryos.


Subject(s)
Embryo, Nonmammalian/drug effects , Fungicides, Industrial/toxicity , Water Pollutants, Chemical/toxicity , Acetylcholinesterase/genetics , Acetylcholinesterase/metabolism , Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Animals , Cyprinidae/embryology , Embryo, Nonmammalian/embryology , Epoxy Compounds/toxicity , Fish Proteins/genetics , Fish Proteins/metabolism , Fluconazole/toxicity , Gene Expression/drug effects , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Imidazoles/toxicity , Nitriles/toxicity , Silanes/toxicity , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Triazoles/toxicity
15.
Chemosphere ; 108: 46-54, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24875911

ABSTRACT

Triazophos (TAP) has been widely used in agriculture for controlling insect pests and is a known organophosphorus pesticide. Due to TAP characteristics, such as high chemical and photochemical stability, its potential toxicity to aquatic organisms has gained great interest. To explore the potential developmental toxicity of TAP, Gobiocypris rarus embryos and larvae were exposed to various concentrations of TAP (0.1-15 mg L(-1)) until 72 h. Results showed that values of 72 h LC50 and EC50 were 7.44 and 5.60 mg L(-1) for embryos, 2.52 and 1.37 mg L(-1) for larvae. Increased malformation, decreased heart rate and body length provide a gradual concentration-dependent pattern. Enzyme activities and mRNA levels were significantly changed even at low concentration (0.05 mg L(-1) for embryos and 0.01 mg L(-(1) for larvae). Overall, the present study points out that TAP is likely a risk to the early development of G. rarus. The information presented in this study will be helpful in better understanding the toxicity induced by TAP in fish embryos and larvae.


Subject(s)
Cyprinidae/growth & development , Embryo, Nonmammalian/drug effects , Organothiophosphates/toxicity , Pesticides/toxicity , Teratogens/toxicity , Triazoles/toxicity , Water Pollutants, Chemical/toxicity , Animals , Cyprinidae/abnormalities , Cyprinidae/embryology , Cyprinidae/genetics , Embryo, Nonmammalian/abnormalities , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , Gene Expression Regulation, Developmental/drug effects , Larva/drug effects , Larva/genetics , Larva/growth & development
16.
Environ Toxicol Pharmacol ; 37(3): 1040-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24762415

ABSTRACT

This study investigated the effects of trifloxystrobin that one strobilurin used widely in the world as an effective fungicidal agent to control Asian soybean rust on aquatic unicellular algae Chlorella vulgaris. We determined the potential toxic effect of trifloxystrobin on C. vulgaris, and found median inhibition concentration (IC(50)) value 255.58 (95% confidence interval, 207.81-330.29)µgL(-1). In addition, the algal cells were obviously depressed or shrunk at different concentrations by electron microscopy. In the study, a real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL, and one energy gene, ATPs. The results showed that trifloxystrobin reduced the transcript abundances of the three genes and enhanced expression of ATPs after 48 and 96 h. The lowest abundances of psaB, psbC and rbcL transcripts in response to trifloxystrobin exposure were 58%, 79% and 60% of those of the control, respectively. For the potential toxic influences, trifloxystrobin could decrease the soluble protein and total antioxidant contents (T-AOC), and increase superoxide dismutase (SOD) and peroxidase (POD) activity with a gradual concentration-response relationship. Overall, the present study demonstrated that trifloxystrobin could affect the activities of antioxidant enzymes, disrupts photosynthesis in C. vulgaris, and damage cellular structure.


Subject(s)
Acetates/toxicity , Anti-Infective Agents/toxicity , Chlorella vulgaris/drug effects , Imines/toxicity , Chlorella vulgaris/physiology , Chlorella vulgaris/ultrastructure , Chloroplast Proton-Translocating ATPases/genetics , Gene Expression Regulation, Plant/drug effects , Methacrylates/toxicity , Microscopy, Electron, Scanning , Oxidative Stress , Peroxidases/metabolism , Photosystem I Protein Complex/genetics , Photosystem II Protein Complex/genetics , Plant Proteins/genetics , RNA, Messenger/metabolism , Ribulose-Bisphosphate Carboxylase/genetics , Strobilurins , Superoxide Dismutase/metabolism
17.
Ecotoxicol Environ Saf ; 98: 297-302, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24210350

ABSTRACT

The strobilurins are used widely in the world as effective fungicidal agents to control Asian soybean rust. In this study, the early life stage of grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China, was chosen to measure the acute toxicity of three common strobilurin-derived fungicides (trifloxystrobin (TFS), azoxystrobin (AZ) and kresoxim-methyl (KM)). As endpoints, normal developmental parameters (lethal concentration (LC50) and average heart rate), expression of relative genes, and three antioxidant enzyme activities in the developing juveniles were recorded during a 48 h exposure. The results revealed that values of LC50 were TFS 0.051 (0.046-0.058) mg L⁻¹, AZ 0.549 (0.419-0.771) mg L⁻¹ and KM 0.338 (0.284-0.407) mg L⁻¹ for juveniles. For the potential toxicity mechanisms, these three fungicides increased catalase (CAT) and peroxidase (POD) activity and decreased superoxide dismutase (SOD) activity, significantly inhibited expressions of three growth-related genes (IGF-1, IGF-2 and GHR) and two energy-related-genes (CCK and PYY), and caused pronounced up-regulation a stress-gene (HSP70). The present study demonstrated potential toxic effects of TFS, AZ and KM on the early development of C. idella. Overall, three strobilurins (TFS, AZ and KM) might cause serious damages to the aquatic species; therefore, their pollution supervision in water ecological environment should be strengthened.


Subject(s)
Acetates/toxicity , Carps/metabolism , Fungicides, Industrial/toxicity , Imines/toxicity , Methacrylates/toxicity , Phenylacetates/toxicity , Pyrimidines/toxicity , RNA, Messenger/metabolism , Animals , Catalase/genetics , Catalase/metabolism , China , Gene Expression , HSP72 Heat-Shock Proteins/genetics , HSP72 Heat-Shock Proteins/metabolism , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Peroxidase/genetics , Peroxidase/metabolism , Receptors, Somatotropin/genetics , Receptors, Somatotropin/metabolism , Strobilurins , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
18.
Zhonghua Yi Xue Za Zhi ; 92(24): 1702-5, 2012 Jun 26.
Article in Chinese | MEDLINE | ID: mdl-22944163

ABSTRACT

OBJECTIVE: To explore the effects of lipopolysaccharide (LPS)-induced myeloid-derived suppressor cells (MDSCs) on the proliferation of spleen T lymphocytes. METHODS: BALB/c mice were randomly divided into two groups: LPS group and normal control group. They were injected intraperitoneally with LPS and normal saline solution respectively. MDSCs were separated with CD11b immunomagnetic beads from the spleen extract of mice. The morphological characteristics of MDCSs were observed by Wright-Giemsa staining and the characteristic molecules on cell surface identified by flow cytometry. And the effects of MDSCs on the in vitro proliferation of T cells were determined by methyl-thiazolyl-tetrazolium bromide (MTT). RESULTS: The proportion of MDSCs in the spleen of the LPS group was much more than that of the normal control group (27.4% ± 6.6% vs 5.1% ± 3.8%; t = 5.06, P = 0.007). CD11b(+)Gr-1(+)MDSCs could be separated by CD11b immunomagnetic beads from the spleen of mice injected with LPS at a high purity of 84.0% ± 4.2%. MTT method showed that the proliferation of T cells decreased significantly after a co-cultivation with CD11b(+)MDSCs versus the control group. And it was positively correlated with the number of MDSCs (F = 46.26, P = 0.000). CONCLUSIONS: A high purity of LPS-induced myeloid-derived suppressor cells may be separated with CD11b immunomagnetic beads. And it has dose-dependent inhibitory effects on the proliferation of the spleen T lymphocytes.


Subject(s)
Cell Proliferation/drug effects , Lipopolysaccharides/adverse effects , Myeloid Cells/drug effects , T-Lymphocytes, Regulatory/drug effects , Animals , Cells, Cultured , Coculture Techniques , Mice , Mice, Inbred BALB C , Myeloid Cells/cytology , Spleen/cytology , T-Lymphocytes, Regulatory/cytology
19.
Zhonghua Yi Xue Za Zhi ; 92(44): 3147-50, 2012 Nov 27.
Article in Chinese | MEDLINE | ID: mdl-23328430

ABSTRACT

OBJECTIVE: To explore the effect and mechanism of lipopolysaccharides (LPS)-induced CD11b⁺Gr-1⁺ myeloid-derived suppressor cells (MDSCs) on airway inflammation in asthmatic mice. METHODS: A total of 34 female BALB/c mice were selected. Among them, 4 mice received an intraperitoneal injection of LPS for inducing the accumulation of MDSCs. And the MDSCs were separated with CD11b immunomagnetic beads from spleen extract. Another 30 mice were randomly divided into normal control, asthmatic and cell treatment groups. The mice in the asthmatic and cell treatment groups were sensitized with ovalbumin by a combination of intraperitoneal injection and challenges to establish the murine asthmatic model. At Days 14 and 21 post-sensitization, the mice in cell treatment group received an intravenous injection of LPS-induced MDSCs. At 24 hours after the last allergen challenge, the number of inflammatory cells were counted and morphological identification of leucocytes in bronchoalveolar lavage fluid (BALF) was performed to analyze the degree of airway inflammation in conjunctions with pathological sections. The BALF and serum levels of interleukin-13 were measured by enzyme-linked immunosorbent assay (ELISA). The number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in peripheral blood was measured by flow cytometry. RESULTS: The total number of cells, the percentage of neutrophils and eosinophils of BALF in the cell treatment group [(17.0 ± 8.3)×104/ml, 11.1% ± 2.0%, 9.8% ± 2.9%] were significantly lower than those in the asthmatic group [(36.0 ± 15.9)×104/ml, 20.8% ± 4.0%, 14.1% ± 4.2%] (P = 0.000, 0.000, 0.011). Compared to the asthmatic group, the BALF and serum levels of IL-13 were significantly lower [(34.7 ± 7.1) vs (105.0 ± 9.0) ng/L, (34.0 ± 4.7) vs (48.1 ± 6.1) ng/L] (both P = 0.000) and the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells increased in peripheral blood (8.0% ± 1.3% vs 5.1% ± 2.1%, P = 0.002) and airway inflammation was significantly relieved in the cell treatment group. CONCLUSION: LPS-induced MDSCs may improve airway inflammation through up-regulating Tregs in peripheral blood and suppressing Th2 effector function in asthmatic mice.


Subject(s)
Asthma/pathology , Inflammation , Lipopolysaccharides/pharmacology , Myeloid Cells/cytology , Animals , Asthma/drug therapy , Bronchoalveolar Lavage Fluid , Female , Interleukin-13/analysis , Interleukin-13/blood , Lung/pathology , Mice , Mice, Inbred BALB C , Myeloid Cells/drug effects , T-Lymphocytes, Regulatory
20.
Zhonghua Yi Xue Za Zhi ; 91(26): 1861-5, 2011 Jul 12.
Article in Chinese | MEDLINE | ID: mdl-22093792

ABSTRACT

OBJECTIVE: To explore whether or not CD8(+)CD28(-)T cell play a pathogenic role in asthma and detect the effects of dexamethasone (DXM). METHODS: A total of 30 mice were randomly divided into 3 groups: asthmatic group, DXM group and control group (n = 10 each). The asthmatic and DXM groups were sensitized twice and inhaled ovalbumin. The DXM Group received an intraperitoneal injection of DXM 1mg/kg before inhaling ovalbumin. After successful modeling, 3 mice were selected randomly from each group to measure the airway responsiveness. Also a bronchoalveolar lavage cytological study was performed and lung tissue sections were prepared for histopathologic examination to evaluate the airway inflammation. The content of IgE in bronchoalveolar lavage fluid (BALF) was detected with a murine IgE ELISA kit. And the fractions of CD8(+)CD28(-)T cell of peripheral blood and BALF were tested by flow cytometry to analyze the correlation between IgE, eosinophils (EOS) of BALF and CD8(+)CD28(-)T cell of blood. RESULTS: The airway hyperresponsiveness in asthmatic and DXM groups were significantly higher than that in the control group. The number of total cells and EOS of BALF in the asthmatic group [(5.56 ± 4.06) × 10(2)/L; (3.29 ± 2.23) × 10(2)/L] were significantly higher than that in control group [(0.91 ± 0.65) × 10(2)/L, P = 0.003; (0.43 ± 0.37) × 10(2)/L, P = 0.001] and DXM group [(2.59 ± 1.69) × 10(2)/L, P = 0.044; (1.11 ± 0.73) × 10(2)/L, P = 0.008]; while the DXM group was insignificantly higher than the control group (P = 0.234, P = 0.363). There were significant differences in the contents of IgE of BALF for the asthmatic, DXM and control groups [(23.85 ± 5.97) g/L, (13.15 ± 2.22) g/L, (6.54 ± 1.03) g/L, F = 38.558, P = 0.000]. The percentages of CD8(+)CD28(-)T cell in peripheral blood in asthmatic and DXM groups [(18.68 ± 4.12)% and (13.43 ± 2.91)%] were significantly higher than those in control mice [(8.43 ± 4.60)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of BALF in asthmatic group and DXM group [(1.25 ± 0.40)% and (0.66 ± 0.49)%] were also significantly higher than those in control mice [(0.21 ± 0.19)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of blood and BALF in the DXM mice were significantly lower than those in asthmatic group. The correlations between IgE (r = 0.864, P = 0.012), EOS (r = 0.804, P = 0.029) and CD8(+)CD28(-)T cell were significant. CONCLUSION: The fraction of CD8(+)CD28(-)T cell is closely correlated with the inflammation of asthmatic airway. The airway hyperresponsiveness and inflammation in asthmatic mice may be relieved by DXM through its effect of inhibiting the expression of CD8(+)CD28(-) T cell.


Subject(s)
Asthma/pathology , Bronchial Hyperreactivity/pathology , Dexamethasone/pharmacology , T-Lymphocytes, Regulatory , Animals , Asthma/metabolism , Bronchial Hyperreactivity/metabolism , Female , Lymphocyte Count , Mice , Mice, Inbred BALB C
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