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1.
Cell ; 187(3): 764-781.e14, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306985

RESUMO

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.


Assuntos
Metabolômica , Gravidez , Animais , Feminino , Humanos , Gravidez/metabolismo , Corticosterona/metabolismo , Metaboloma/fisiologia , Placenta/metabolismo , Pré-Eclâmpsia , Primatas/metabolismo
2.
Anal Chem ; 96(2): 787-793, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38170819

RESUMO

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.


Assuntos
Neoplasias , Selênio , Humanos , Espectrometria de Massas em Tandem/métodos , Aldeídos
3.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1641-1660, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621949

RESUMO

This study explored the existence forms(original constituents and metabolites) of Tiantian Capsules, Aloe, and Tiantian Capsules without Aloe in rats for the first time, aiming to clarify the contribution of Aloe to the existence form of Tiantian Capsules. Rats were administrated with corresponding drugs by gavage once a day for seven consecutive days. All urine and feces samples were collected during the seven days of administration, and blood samples were collected 0.5, 1, and 1.5 h after the last administration. UHPLC-Q-TOF-MS was employed to detect and identify the original constituents and metabolites in the samples. A total of 34, 28, and 2 original constituents and 64, 94, and 0 metabolites were identified in the samples of rats administrated with Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe, respectively. The main metabolic reactions were methylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. This study clarified for the first time the existence forms and partial metabolic pathways of Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe in rats, laying a foundation for revealing their effective forms. The findings are of great significance to the research on the functioning mechanism and quality control of Aloe and Tiantian Capsules.


Assuntos
Aloe , Medicamentos de Ervas Chinesas , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Administração Oral , Fezes , Cápsulas
4.
J Fish Dis ; 46(9): 967-976, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37329523

RESUMO

Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 µM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 µM for 50% maximal effect (EC50 ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-ß and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius.


Assuntos
Anti-Helmínticos , Doenças dos Peixes , Parasitos , Trematódeos , Animais , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/parasitologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Citocinas , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico
5.
Anal Chem ; 93(3): 1749-1756, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33351590

RESUMO

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.


Assuntos
Acetilcisteína/análise , Cisteína/análise , Dipeptídeos/análise , Corantes Fluorescentes/química , Glutationa/análise , Papel , Selênio/química , Técnicas Biossensoriais , Cisteína/análogos & derivados , Humanos , Espectrometria de Massas
6.
Fish Shellfish Immunol ; 102: 389-399, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380168

RESUMO

Infectious hematopoietic necrosis (IHN) caused by the viral pathogen infectious hematopoietic necrosis virus (IHNV) is a highly contagious disease of salmonid species, resulting in significant economic impact. The previous study showed a hydroxycoumarin derivative 7-[6-(2-methylimidazole) hexyloxy] coumarin (D5) significantly inhibited spring viraemia of carp virus (SVCV) infection, suggesting that D5 may be useful as a potential anti-IHNV agent. In this study, D5 at the concentration of up to 10 mg/L significantly inhibited IHNV replication in epithelioma papulosum cyprini (EPC) cells with a maximum inhibitory rate of >90%, maintained mitochondrial membrane potential (ΔΨm) levels, and decreased IHNV-induced apoptosis in virus-infected cells. As the consequence of protection on mitochondria, D5 enhanced antioxidant enzyme activities and decreased reactive oxygen species (ROS) to maintain the antioxidant-oxidant balance of IHNV-infected EPC cells. For in vivo study, D5 via intraperitoneal injection exhibited an anti-IHNV effect in the virus-infected fish by substantially enhancing the survival rate. Meanwhile, up-regulation of six interferon (IFN) related gene expressions demonstrated that D5 may activate IFN-related expressions for inhibiting IHNV replication during the early stage of viral infection, which is beneficial for the continuous antiviral action on controlling low viral loads in rainbow trout juvenile. Thus, D5 effective regulated IHNV-induced undesirable conditions to be an excellent potential therapeutic agent against IHNV infection.


Assuntos
Antivirais/farmacologia , Cumarínicos/farmacologia , Cyprinidae , Doenças dos Peixes/prevenção & controle , Vírus da Necrose Hematopoética Infecciosa/efeitos dos fármacos , Oncorhynchus mykiss , Infecções por Rhabdoviridae/veterinária , Animais , Linhagem Celular , Infecções por Rhabdoviridae/prevenção & controle
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(12): 1320-1325, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33328004

RESUMO

A boy, aged 2 years and 4 months, had a sudden onset of blepharoptosis of the right eyelid, accompanied by the mouth deviated to the right side, drinking cough, nystagmus, and developmental regression. Cranial MRI showed softening lesions formed after infarction of the right dorsolateral medulla oblongata, while head CT angiography showed no imaging of the proximal part of the V4 segment of the right vertebral artery. The child was diagnosed with dorsolateral medulla oblongata syndrome and was treated with gamma globulin to regulate immune function, with mannitol to reduce neuronal edema, with low-molecular-weight heparin sodium to improve local hypercoagulation of occluded blood vessels, with hyperbaric oxygen to improve local ischemia and hypoxia and promote the recovery of brain function, and with neuromuscular electrical stimulation to promote the recovery of neuromuscular function. Before discharge, only mild right ataxia and Horner syndrome remained. This article reports the first case of infantile dorsolateral medulla oblongata syndrome and provides experience for the diagnosis and treatment of the disease.


Assuntos
Blefaroptose/etiologia , Disartria/etiologia , Síndrome Medular Lateral/diagnóstico , Bulbo/diagnóstico por imagem , Pré-Escolar , Humanos , Síndrome Medular Lateral/complicações , Imageamento por Ressonância Magnética , Masculino
8.
J Sex Med ; 15(1): 29-42, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29289372

RESUMO

BACKGROUND: Although it is widely acknowledged that genetic and environmental factors are involved in the development of male homosexuality, the causes are not fully understood. AIM: To explore the association and interaction of childhood abuse experiences and genetic variants of the catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) genes with the development of male homosexuality. METHODS: A case-control study of 537 exclusively homosexual men and 583 exclusively heterosexual men was conducted, with data collected from March 2013 to August 2015. Data were analyzed using χ2 tests and logistic regression models. OUTCOMES: Sociodemographic characteristics, childhood abuse experiences, and polymorphisms of COMT at rs4680, rs4818, and rs6267 and MTHFR at rs1801133. RESULTS: More frequent occurrence of physical (adjusted odds ratio [aOR] = 1.78), emotional (aOR = 2.07), and sexual (aOR = 2.53) abuse during childhood was significantly associated with the development of male homosexuality. The polymorphisms of MTHFR at rs1801133 and COMT at rs4818 also were significantly associated with the development of male homosexuality in the homozygote comparisons (T/T vs C/C at rs1801133, aOR = 1.68; G/G vs C/C at rs4818, aOR = 1.75). In addition, significant interaction effects between childhood abuse experiences and the COMT and MTHFR genetic variants on the development of male homosexuality were found. CLINICAL TRANSLATION: This is the first time that an association of childhood abuse, COMT and MTHFR genetic variants, and their interactions with development of male homosexuality was exhaustively explored, which could help provide new insight into the etiology of male homosexuality. STRENGTHS AND LIMITATIONS: Because homosexual men are a relatively obscure population, it was impossible to select the study participants by random sampling, which could lead to selection bias. In addition, because this was a case-control study, recall bias was inevitable, and we could not verify causality. CONCLUSIONS: Childhood abuse and the COMT and MTHFR genetic variants could be positively associated with the development of homosexuality. However, it remains unknown how these factors jointly play a role in the development of homosexuality, and more studies in different ethnic populations and with a larger sample and a prospective design are required to confirm our findings. Qin J-B, Zhao G-L, Wang F, et al. Childhood Abuse Experiences and the COMT and MTHFR Genetic Variants Associated With Male Sexual Orientation in the Han Chinese Populations: A Case-Control Study. J Sex Med 2018;15:29-42.


Assuntos
Catecol O-Metiltransferase/genética , Maus-Tratos Infantis/estatística & dados numéricos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Comportamento Sexual , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Adulto Jovem
9.
Inorg Chem ; 57(7): 3596-3601, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29206034

RESUMO

Functional molecular capsules have attracted a lot of attention in recent years because of their potential applications as chemosensors, catalysis, drug carriers, and so on. We report here the coordination-directed self-assembly of a fluorescent-lantern-type molecular capsule from four tetraphenylethylene-based ditopic ligands and two square-planar palladium(II) ions. The capsule has been thoroughly characterized by UV-vis, 1D/2D NMR, electrospray ionization time-of-flight mass spectrometry, and single-crystal X-ray diffraction studies. The aggregation-induced emission performance of the capsule has been studied by tuning the ratio of mixed solvents. Moreover, with an open cavity, the fluorescence of the capsule also displays anion sensitivity, with the best turn-on responsiveness observed for HCO3-, demonstrating for the first time an encapsulation-induced emission property.

10.
Molecules ; 23(2)2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29425118

RESUMO

Materials with aggregation-induced emission (AIE) properties have received increased attention recently due to their potential applications in light-emitting devices, chemo/biosensors and biomedical diagnostics. In general, AIE requires the forced aggregation of the AIEgens induced by the poor solvent or close arrangement of AIEgens covalently attached to polymer chains. Here, we report two coordination-enhanced fluorescent supramolecular complexes featuring hierarchically restricted intramolecular motions via the self-assembly of tetraphenylethylene (TPE)-based tetra-dentate (La) and bidentate (Lb) ligands and the cis-Pd(en)(NO3)2 (en = ethylenediamine) unit. While the free ligands are non-emissive in dilute solution and show typical AIE properties in both mixed solvent system and the solid state, the self-assembled complexes maintain their fluorescent nature in the solution state. In particular, the Pd4(La)2 complex shows remarkable 6-fold fluorescent enhancement over La in dilute solution. We anticipate that these kinds of coordination-enhanced emissive supramolecules will find applications in biomedical sensing or labeling.


Assuntos
Complexos de Coordenação/química , Corantes Fluorescentes/química , Paládio/química , Estilbenos/química , Dimerização , Isomerismo , Ligantes , Estrutura Molecular , Espectrometria de Fluorescência/métodos
11.
J Clean Prod ; 177: 464-473, 2018 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-29479147

RESUMO

Based on long-term monitoring conducted in Chang-ning county, a pilot site of the 'Grain for Green Program' (GFGP), an integrated emergy and economic method was applied to evaluate the dynamic ecological-economic performance of 3 kinds of bamboo systems planted on sloping farmland. The results confirmed the positive effects of all 3 kinds of bamboo systems on water conservation and soil erosion control. The benefits gained progressively increased during the first 8 years after conversion, going from 4639 to 16127 EMyuan/ha/yr on average. All three bamboo plantations were much more sustainable than common agricultural crops planted on sloping land (CP) on both the short and long-term scales with their Emergy Sustainability Index (ESI) and Emergy Index for Sustainable Development (EISD), respectively, being 14.07-325.71 and 80.35-265.80 times that of CP. However, all 3 bamboo plantations had a Net Economic Benefit (NEB) less than that of CP during the first 8 years after conversion. Even with the government-mandated ecological compensation applied, the annual NEBECs of the Bambusa rigida (BR) and Phyllostachys pubescense (PP) plantations were, respectively, 3922.03 and 7422.77 yuan/ha/yr lower than the NEB of CP. Emergy-based evaluation of ecosystem services provides an objective reference for applying ecological compensation in strategy-making, but it cannot wholly solve the economic viability problem faced by all bamboo plantations. Inter-planting annual herbs or edible fungus, such as Dictyophora echinovolvata, within bamboo forests, especially in young bamboo plantations, might be a direction for optimizing bamboo cultivation that would improve its economic viability.

12.
Bioorg Med Chem Lett ; 27(15): 3310-3316, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28651981

RESUMO

To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC50=2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs.


Assuntos
Anti-Helmínticos/química , Anti-Helmínticos/farmacologia , Doenças dos Peixes/tratamento farmacológico , Furanos/química , Furanos/farmacologia , Carpa Dourada/parasitologia , Helmintíase Animal/tratamento farmacológico , Lignanas/química , Lignanas/farmacologia , Platelmintos/efeitos dos fármacos , Animais , Anti-Helmínticos/síntese química , Furanos/síntese química , Lignanas/síntese química , Drogas Veterinárias/síntese química , Drogas Veterinárias/química , Drogas Veterinárias/farmacologia
14.
Bioorg Med Chem Lett ; 26(20): 5039-5043, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27617878

RESUMO

With an intention to find more potent anti-parasite agents, four bromoalkane substituted coumarin derivatives (1-4) and twenty coumarin-imidazole hybrid derivatives were synthesized and screened for their anthelmintic activity and the acute toxicity. Anti-parasites results confirmed that most coumarin derivatives retained their anthelmintic activity against Dactylogyrus intermedius at the dose range from 1 to 10mg/L. Among the candidates, compound 23 showed the best anthelmintic activity than other compounds against D. intermedius infestation with EC50 value of 0.85mg/L. The structure-activity relationship analysis confirmed that the anthelmintic activities of derivatives were determined by the length of 'linker' (R1substitute position) and the substitute group in R2 position. The active data confirmed that six carbon atoms length of 'linker' and benzimidazole substitute group can increased the anthelmintic activity of compound, significantly. On the basis of these results, compound 23 can be used as a potential lead compound for the development of commercial drug against D. intermedius.


Assuntos
Anti-Helmínticos/síntese química , Anti-Helmínticos/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Animais , Anti-Helmínticos/química , Cumarínicos/química , Carpa Dourada , Imidazóis/química , Relação Estrutura-Atividade
15.
Fish Shellfish Immunol ; 55: 516-22, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27343373

RESUMO

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.


Assuntos
Aeromonas hydrophila/imunologia , Vacinas Bacterianas/imunologia , Carpas , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Nanotubos de Carbono , Animais , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Imunidade Inata , Distribuição Aleatória , Vacinas de DNA/imunologia
16.
J Am Chem Soc ; 137(26): 8550-5, 2015 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-26065490

RESUMO

Coordination-directed self-assembly has become a well-established technique for the construction of functional supramolecular structures. In contrast to the most often exploited transition metals, trivalent lanthanides Ln(III) have been less utilized in the design of polynuclear self-assembled structures despite the wealth of stimulating applications of these elements. In particular, stereochemical control in the assembly of lanthanide chiral cage compounds is not easy to achieve in view of the usually large lability of the Ln(III) ions. We report here the first examples of stereoselective self-assembly of chiral luminescent europium coordination tetrahedral cages and their intriguing self-sorting behavior. Two pairs of R and S ligands are designed on the basis of the pyridine-2,6-dicarboxamide coordination unit, bis(tridentate) L1 and tris(tridentate) L2. Corresponding chiral Eu4(L1)6 and Eu4(L2)4 topological tetrahedral cages are independently assembled via edge- and face-capping design strategies, respectively. The chirality of the ligand is transferred during the self-assembly process to give either Δ or Λ metal stereochemistry. The self-assembled cages are characterized by NMR, high-resolution ESI-TOF-MS, and in one case by X-ray crystallography. Strict control of stereoselectivity is confirmed by CD spectroscopy and NMR enantiomeric differentiation experiments. Narcissistic self-sorting is observed in the self-assembly process when two differently shaped ligands L1 and L2 are mixed. More impressively, distinct self-sorting behavior between Eu4(L1)6 and Eu4(L2)4 coordination cages is observed for the first time when racemic mixtures of ligands are used. We envisage that chiral luminescent lanthanide tetrahedral cages could be used in chiroptical probes\sensors and enantioselective catalysis.

17.
Fish Shellfish Immunol ; 42(2): 325-34, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25463298

RESUMO

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.


Assuntos
Proteínas do Capsídeo/imunologia , Carpas , Doenças dos Peixes/imunologia , Nanotubos de Carbono/análise , Infecções por Reoviridae/veterinária , Reoviridae/imunologia , Vacinas Virais/imunologia , Animais , Proteínas do Capsídeo/genética , Imunidade Inata , Imunização/veterinária , Reoviridae/genética , Infecções por Reoviridae/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas Virais/genética
18.
Fish Shellfish Immunol ; 47(2): 732-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26497092

RESUMO

To reduce the lethal hemorrhagic disease caused by grass carp reovirus (GCRV) and improve the production of grass carp, efficient and economic prophylactic measure against GCRV is the most pressing desired for the grass carp farming industry. In this work, a novel SWCNTs-pEGFP-vp5 DNA vaccine linked vp5 recombinant in the form of plasmid pEGFP-vp5 and ammonium-functionalized SWCNTs by a chemical modification method was prepared to enhance the efficacy of a vp5 DNA vaccine against GCRV in juvenile grass carp. After intramuscular injection (1, 2.5 and 5 µg) and bath administration (1, 10, and 20 mg/L), the ability of the different immune treatments to induce transgene expression was analyzed. The results showed that higher levels of transcription and expression of vp5 gene could be detected in muscle tissues of grass carp in SWCNTs-pEGFP-vp5 treatment groups compare with naked pEGFP-vp5 treatment groups. Moreover, antibody levels, immune-related genes, and relative percentage survival were significantly enhanced in fish immunized with SWCNTs-pEGFP-vp5 vaccine. In addition, we found that a good immune protective effect was observed in bath immunization group; which at a concentration of 20 mg/L could reach the similar relative percentage survival (approximately 100%) in injection group at a dose of 5 µg. All these results indicated that ammonium-functionalized SWCNTs could provide extensive application prospect to aquatic vaccine and might be used to vaccinate fish by intramuscular injection or bath administration method.


Assuntos
Carpas , Doenças dos Peixes/imunologia , Nanotubos de Carbono , Infecções por Reoviridae/veterinária , Reoviridae/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Doenças dos Peixes/virologia , Imunização , Infecções por Reoviridae/imunologia , Infecções por Reoviridae/virologia
19.
Fish Shellfish Immunol ; 42(1): 213-20, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25462556

RESUMO

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.


Assuntos
Aeromonas hydrophila/imunologia , Vacinas Bacterianas/farmacologia , Carpas , Doenças dos Peixes/microbiologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Nanotubos de Carbono , Análise de Variância , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/administração & dosagem , Primers do DNA/genética , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/veterinária , Ensaio de Imunoadsorção Enzimática , Infecções por Bactérias Gram-Negativas/prevenção & controle , Reação em Cadeia da Polimerase em Tempo Real , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/farmacologia
20.
Fish Shellfish Immunol ; 45(1): 175-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25862971

RESUMO

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.


Assuntos
Aeromonas hydrophila/imunologia , Vacinas Bacterianas/imunologia , Carpas , Doenças dos Peixes/prevenção & controle , Microbioma Gastrointestinal , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata , Animais , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Vacinas Sintéticas/imunologia
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