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1.
Front Plant Sci ; 15: 1386109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708391

RESUMO

Compared to conventional irrigation and fertilization, the Water-fertilizer coupling can significantly enhance the efficiency of water and fertilizer utilization, thereby promoting crop growth and increasing yield. Targeting the challenges of poor crop growth, low yield, and inefficient water and fertilizer utilization in the arid region of northwest China under conventional irrigation and fertilization practices. Therefore, a two-year on-farm experiment in 2022 and 2023 was conducted to study the effects of water-fertilizer coupling regulation on pumpkin growth, yield, water consumption (ET), and water and fertilizer use efficiency. Simultaneously the comprehensive evaluation of multiple objectives was carried out using principal component analysis (PCA) methods, so as to propose an suitable water-fertilizer coupling regulation scheme for the region. The experiment was set up as a two-factor trial using water-fertilizer integration technology under three irrigation volume (W1 = 37.5 mm, W2 = 45.5 mm, W3 = 52.5mm) and three organic fertilizer application amounts (F1 = 3900-300 kg ha-1, F2 = 4800-450 kg·ha-1, F3 = 5700-600 kg·ha-1), with the traditional irrigation and fertilization scheme from local farmers as control treatments (CK). The results indicated that irrigation volume and organic fertilizer application significantly affected pumpkin growth, yield, and water and fertilizer use efficiency (P<0.05). Pumpkin yield increased with increasing irrigation volume. Increasing organic fertilizer levels within a certain range benefited pumpkin plant growth, dry matter accumulation, and yield, however, excessive application beyond a certain level had inhibited effects on those. The increased fertilizer application under the same irrigation volume enhanced the efficiency of water and fertilizer utilization. However excessive irrigation only resulted in inefficient water consumption, reducing the water and fertilizer use efficiency. The Comprehensive evaluation by PCA revealed that the F2W3 treatment outperformed all the others, effectively addressing the triple objectives of increasing production, improving efficiency, and promoting green production. Therefore, F2W3 (Irrigation volume: 52.5 mm; Fertilizer application amounts: 4800-450 kg/ha-1) as a water and fertilizer management scheme for efficient pumpkin production in the arid region of northwest China.

2.
Chin J Nat Med ; 22(4): 365-374, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38658099

RESUMO

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C (PKC). The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20, C3/C4, and C9 of phorbol. Concurrently, the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand complex. The influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further exploration. This research entailed the hydrolysis of phorbol, producing seco-cyclic phorbol derivatives. The anti-HIV-1 efficacy of these derivatives was assessed, and the affinity constant (Kd) for PKC-δ protein of selected seco-cyclic phorbol derivatives was determined through isothermal titration calorimetry. The findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding affinity. Remarkably, compound S11, with an EC50 of 0.27 µmol·L-1 and a CC50 of 153.92 µmol·L-1, demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription (ssDNA and 2LTR), likely acting at the viral entry stage, yet showed no affinity for the PKC-δ protein. These results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.


Assuntos
Fármacos Anti-HIV , HIV-1 , HIV-1/efeitos dos fármacos , Humanos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Ésteres de Forbol/farmacologia , Ésteres de Forbol/química , Estrutura Molecular , Proteína Quinase C/metabolismo , Proteína Quinase C/química , Relação Estrutura-Atividade
3.
J Hazard Mater ; 470: 134151, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38554517

RESUMO

Ground-level ozone ranks sixth among common air pollutants. It worsens lung diseases like asthma, emphysema, and chronic bronchitis. Despite recent attention from researchers, the link between exhaled breath and ozone-induced injury remains poorly understood. This study aimed to identify novel exhaled biomarkers in ozone-exposed mice using ultra-sensitive photoinduced associative ionization time-of-flight mass spectrometry and machine learning. Distinct ion peaks for acetonitrile (m/z 42, 60, and 78), butyronitrile (m/z 70, 88, and 106), and hydrogen sulfide (m/z 35) were detected. Integration of tissue characteristics, oxidative stress-related mRNA expression, and exhaled breath condensate free-radical analysis enabled a comprehensive exploration of the relationship between ozone-induced biological responses and potential biomarkers. Under similar exposure levels, C57BL/6 mice exhibited pulmonary injury characterized by significant inflammation, oxidative stress, and cardiac damage. Notably, C57BL/6 mice showed free radical signals, indicating a distinct susceptibility profile. Immunodeficient non-obese diabetic Prkdc-/-/Il2rg-/- (NPI) mice exhibited minimal biological responses to pulmonary injury, with little impact on the heart. These findings suggest a divergence in ozone-induced damage pathways in the two mouse types, leading to alterations in exhaled biomarkers. Integrating biomarker discovery with comprehensive biopathological analysis forms a robust foundation for targeted interventions to manage health risks posed by ozone exposure.


Assuntos
Biomarcadores , Testes Respiratórios , Aprendizado de Máquina , Camundongos Endogâmicos C57BL , Ozônio , Animais , Ozônio/toxicidade , Biomarcadores/metabolismo , Biomarcadores/análise , Masculino , Estresse Oxidativo/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Camundongos , Espectrometria de Massas , Expiração , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo
4.
Chin J Nat Med ; 22(2): 146-160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38342567

RESUMO

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L-1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.


Assuntos
Fármacos Anti-HIV , Forbóis , Simulação de Acoplamento Molecular , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Forbóis/química , Forbóis/farmacologia , Ésteres de Forbol/farmacologia , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , Relação Estrutura-Atividade
5.
J Agric Food Chem ; 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37022303

RESUMO

Natural food preservatives are being sought extensively as a safe alternative to chemical food preservatives. This study aimed to identify potential natural preservatives from herbs using single-photon ionization time-of-flight mass spectrometry (SPI-TOF-MS). Five Artemisia species and four other herbs were analyzed, and the random forest (RF) algorithm was used to simulate olfaction and distinguish the Artemisia species by identifying the characteristic peaks of volatile terpenoids (VTPs). Results showed that the terpenoid synthase (TPS) gene family was expanded in Artemisia species, potentially contributing to the increased production of VTPs, which have potential as natural preservatives and specifically identify these species. The limits of detections (LODs) for principle VTPs in Artemisia species were as low as 22-39 parts-per-trillion-by-volume (pptv) using SPI-TOF-MS. This study highlights the potential for headspace mass spectrometry to be used in the development of natural preservatives and the identification of plant species.

6.
Chemosphere ; 307(Pt 3): 136059, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35977569

RESUMO

The rapid reproduction of foodborne bacteria in food packaging threatens the health of consumers, the massive use and waste of packaging also causes serious environmental pollution. In this study, novel biodegradable antibacterial membranes based on silver-modified carboxymethyl chitosan (Ag-CMCS) were prepared. Polylactic acid (PLA) and polybutylene adipate-co-terephthalate (PBAT) were used as the base membrane materials. Characterization of the prepared membranes was performed by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), atomic force microscope (AFM), X-ray photoelectron spectroscopy (XPS), water contact angle, and so on. Especially, the silver on the surface of Ag-CMCS was proved to be metallic silver. For the first cycle of zone of inhibition test, the diameter of inhibition zone could reach up to 17 mm while the mass of silver released was negligible. The prepared antibacterial membranes could kill almost 100% of bacteria under certain conditions and inhibition zone still existed after more than 7 cycles of tests, indicating the prepared antibacterial membranes were effective. This study could provide new ideas for preparing efficient and environment-friendly antibacterial food packaging membranes.


Assuntos
Quitosana , Nanopartículas Metálicas , Adipatos , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Quitosana/farmacologia , Nanopartículas Metálicas/química , Poliésteres , Polímeros/farmacologia , Prata/química , Prata/farmacologia , Água
7.
Chemosphere ; 295: 133963, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35167836

RESUMO

Although ion exchange resins (IERs) have been extensively adopted in water treatment, there are no reports on the application thereof for synthesizing antibacterial materials against pathogenic bacteria. The present study is the first in which the ion exchange characteristic of IERs was utilized to introduce silver ions that possess efficient antibacterial properties. The resulting antibacterial materials were incorporated into polylactic acid (PLA) and/or polybutylene adipate terephthalate (PBAT) to prepare antibacterial membranes. XPS spectra revealed the occurrence of in-situ reduction of silver ions to metallic silver, which was preferable since the stability of silver in the materials was improved. EDS mapping analysis indicated that the distribution of silver was consistent with the distribution of sulfur in the membranes, verifying the ion exchange methodology proposed in the present study. To investigate the antibacterial performance of the prepared membranes, zone of inhibition tests and bacteria-killing tests were performed. The results revealed that neither bare polymeric membranes of PLA and PBAT nor IER-incorporated polymeric membranes exhibited noticeable antibacterial activities. In comparison, the antibacterial membranes demonstrated effective and sustainable antibacterial activities against pathogenic bacteria Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The prepared antibacterial membranes exhibited potential in food-related applications such as food packaging to delay food spoilage due to microbial growth.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Escherichia coli , Resinas de Troca Iônica , Staphylococcus aureus
8.
Mol Pharm ; 19(2): 661-673, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35040326

RESUMO

Intracellular delivery of protein therapeutics remains a significant challenge limiting the majority of clinically available protein drugs to extracellular targets. Strategies to deliver proteins to subcellular compartments have traditionally relied on cell-penetrating peptides, which can drive enhanced internalization but exhibit unreliable activity and are rarely able to target specific cells, leading to off-target effects. Moreover, few design rules exist regarding the relative efficacy of various endosomal escape strategies in proteins. Accordingly, we developed a simple fusion modification approach to incorporate endosomolytic peptides onto epidermal growth factor receptor (EGFR)-targeted protein conjugates and performed a systematic comparison of the endosomal escape efficacy, mechanism of action, and capacity to maintain EGFR-targeting specificity of conjugates modified with four different endosomolytic sequences of varying modes of action (Aurein 1.2, GALA, HA2, and L17E). Use of the recently developed Gal8-YFP assay indicated that the fusion of each endosomolytic peptide led to enhanced endosomal disruption. Additionally, the incorporation of each endosomolytic peptide increased the half-life of the internalized protein and lowered lysosomal colocalization, further supporting the membrane-disruptive capacity. Despite this, only EGFR-targeted conjugates modified with Aurein 1.2 or GALA maintained EGFR specificity. These results thus demonstrated that the choice of endosomal escape moiety can substantially affect targeting capability, cytotoxicity, and bioactivity and provided important new insights into endosomolytic peptide selection for the design of targeted protein delivery systems.


Assuntos
Neoplasias da Mama , Peptídeos Penetradores de Células , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Peptídeos Penetradores de Células/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Endossomos/metabolismo , Receptores ErbB/metabolismo , Feminino , Humanos
9.
Chemosphere ; 291(Pt 3): 133106, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34848235

RESUMO

In order to reduce foodborne diseases caused by bacterial infections, antibacterial membranes have received increasing research interests in recent years. In this study, highly effective antibacterial membranes were prepared using biodegradable polymers, including polylactic acid (PLA), polybutylene adipate terephthalate (PBAT), and carboxymethyl cellulose (CMC). The cation exchange property of CMC was utilized to introduce silver to prepare antibacterial materials. The presence of silver in the membranes was confirmed by EDS mapping, and the reduction of silver ions to metallic silver was confirmed by the Ag3d XPS spectrum which displayed peaks at 374.46 eV and 368.45 eV, revealing that the oxidation state of silver changed to zero. Two common pathogenic bacteria, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were used to investigate the antibacterial performance of the prepared membranes. Zone of inhibition and bacteria-killing tests revealed that the antibacterial membranes were efficient in inhibiting the growth of bacteria (diameters of inhibition zone ranged from 16 mm to 19 mm for fresh membranes) and capable of killing 100% of bacteria under suitable conditions. Furthermore, after 6 cycles of continuous zone of inhibition tests, the membranes still showed noticeable antibacterial activities, which disclosed the sustainable antibacterial properties of the membranes.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus , Antibacterianos/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana , Polímeros
10.
Bioorg Med Chem Lett ; 50: 128319, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34403728

RESUMO

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , HIV-1/fisiologia , Ésteres de Forbol/química , Ésteres de Forbol/farmacologia , Replicação Viral/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
11.
Environ Sci Pollut Res Int ; 28(39): 54511-54530, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34431060

RESUMO

Environment protection and food safety are two critical issues in the world. In this review, a novel approach which integrates statistical study and subjective discussion was adopted to review recent advances on environment and food safety. Firstly, a scientometric-based statistical study was conducted based on 4904 publications collected from the Web of Science Core Collection database. It was found that the research on environment and food safety was growing steadily from 2001 to 2020. Interestingly, the statistical analysis of most-cited papers, titles, abstracts, keywords, and research areas revealed that the research on environment and food safety was diverse and multidisciplinary. In addition to the scientometric study, strategies to protect environment and ensure food safety were critically discussed, followed by a discussion on the emerging research topics, including emerging contaminates (e.g., microplastics), rapid detection of contaminants (e.g., biosensors), and environment friendly food packaging materials (e.g., biodegradable polymers). Finally, current challenges and future research directions were proposed.


Assuntos
Poluição Ambiental , Inocuidade dos Alimentos , Plásticos , Monitoramento Ambiental
12.
Front Immunol ; 10: 2995, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31969884

RESUMO

To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.


Assuntos
Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Peptídeos/química , Peptídeos/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Sequência de Aminoácidos , Animais , Ligação de Hidrogênio , Modelos Moleculares , Síndrome Respiratória e Reprodutiva Suína/virologia , Conformação Proteica , Dobramento de Proteína , Multimerização Proteica , Análise Espectral , Relação Estrutura-Atividade , Suínos
13.
J Sci Food Agric ; 98(12): 4420-4426, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29460280

RESUMO

BACKGROUND: Sauropus spatulifolius Beille (named 'Long-Li-Ye' in China) is used to make 'herbal tea' to prevent pneumonia. This study aimed to evaluate the antioxidant activities in vitro and the protective effects of Long-Li-Ye on acute lung injury (ALI) induced by lipopolysaccharide (LPS). RESULTS: The supernatant after ethanol addition to Long-Li-Ye water extract (LLYCSL) and the resin eluting fraction of LLYCSL (LLY40) showed strong antioxidant activities in vitro. LLYCSL and LLY40 could attenuate ALI via decreasing myeloperoxidase activity, increasing superoxide dismutase activity and decreasing the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6. In addition, LLY40 could increase catalase activity, increase the levels of IL-10, IL-4 and IL-13 and decrease the TNF-α/IL-10 ratio. CONCLUSION: Long-Li-Ye could be used as a natural antioxidant for food production and functional food or dietary supplementation for people with ALI. © 2018 Society of Chemical Industry.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Magnoliopsida/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , China , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Peroxidase/genética , Peroxidase/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
J Virol ; 85(22): 11709-24, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21900158

RESUMO

The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1 0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide-SLA-1 0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1 0401 is that Arg(156) has a "one-ballot veto" function in peptide binding, due to its flexible side chain. S-OIV(NW9) and Ebola(AY9) bind SLA-1 0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are "featured" peptides presented by this SLA. Further analyses showed that SLA-1 0401 and human leukocyte antigen (HLA) class I HLA-A 0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1 0401 was proposed, and thermostabilities of key peptide-SLA-1 0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.


Assuntos
Apresentação de Antígeno , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe I/química , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Animais , Dicroísmo Circular , Cristalografia por Raios X , Ebolavirus/imunologia , Epitopos de Linfócito T/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Dobramento de Proteína , Estabilidade Proteica , Homologia de Sequência , Suínos
15.
Artigo em Inglês | MEDLINE | ID: mdl-21543863

RESUMO

In order to illustrate the structure of the swine MHC class I (SLA-I) molecule and to evaluate the cytotoxic T lymphocyte (CTL) response against porcine reproductive and respiratory syndrome virus (PRRSV), the ternary complex of the SLA-I molecule termed SLA-1*1502 with ß(2)-microglobulin and the CTL epitope TMPPGFELY (PRRSV-NSP9(TY9)) derived from PRRSV nonstructural protein 9 (residues 198-206) was assembled and crystallized. The crystal diffracted X-rays to 2.2 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 66.1, b = 74.1, c = 98.6 Å; it contained one molecule in the asymmetric unit. The Matthews coefficient and the solvent content were calculated to be 2.74 Å(3) Da(-1) and 55.17%, respectively. The results will be helpful in obtaining insight into the structural basis of the presentation of viral epitopes by SLA-I.


Assuntos
Antígenos de Histocompatibilidade Classe I/química , Suínos/imunologia , Sequência de Aminoácidos , Animais , Cristalização , Cristalografia por Raios X , Antígenos de Histocompatibilidade Classe I/imunologia , Complexo Principal de Histocompatibilidade , Dados de Sequência Molecular , Alinhamento de Sequência
16.
J Virol ; 85(12): 6038-48, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21450819

RESUMO

The presentation of viral peptide epitopes to host cytotoxic T lymphocytes (CTLs) is crucial for adaptive cellular immunity to clear the virus infection, especially for some chronic viral infections. Indeed, hosts have developed effective strategies to achieve this goal. The ideal scenario would be that the peptide epitopes stimulate a broad spectrum of CTL responses with diversified T-cell receptor (TCR) usage (the TCR repertoire). It is believed that a diversified TCR repertoire requires a "featured" peptide to be presented by the host major histocompatibility complex (MHC). A featured peptide can be processed and presented in a number of ways. Here, using the X-ray diffraction method, the crystal structures of an antigenic peptide derived from rinderpest virus presented by bovine MHC class I N*01801 (BoLA-A11) have been solved, and two distinct conformations of the presented peptide are clearly displayed. A detailed analysis of the structure and comparative sequences revealed that the polymorphic amino acid isoleucine 73 (Ile73) is extremely flexible, allowing the MHC groove to adopt different conformations to accommodate the rinderpest virus peptide. This makes the peptide more featured by exposing different amino acids for T-cell recognition. The crystal structures also demonstrated that the N*01801 molecule has an unusually large A pocket, resulting in the special conformation of the P1 residue at the N terminus of the peptide. We propose that this strategy of host peptide presentation might be beneficial for creating a diversified TCR repertoire, which is important for a more-effective CTL response.


Assuntos
Epitopos de Linfócito T/química , Antígenos de Histocompatibilidade Classe I/imunologia , Fragmentos de Peptídeos/química , Conformação Proteica , Vírus da Peste Bovina/imunologia , Sequência de Aminoácidos , Animais , Bovinos , Cristalografia por Raios X , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Relação Estrutura-Atividade , Linfócitos T Citotóxicos/imunologia
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