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1.
Eur J Med Chem ; 275: 116575, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38865744

RESUMO

Hepatitis B virus (HBV) infection, as a serious global public health issue, is closely related to the immune dysfunction. Herein, thirty-seven 1-(indolin-1-yl)-2-(thiazol-4-yl)ethan-1-one derivatives were prepared as potential immunomodulatory anti-HBV agents. Anti-HBV activity evaluation confirmed compound 11a could significantly suppress the HBV DNA replication in both wild and resistant HBV stains, with IC50 values of 0.13 µM and 0.36 µM, respectively. Preliminary action mechanism studies showed that 11a had an inhibitory effect on cellular HBsAg secretion and could effectively activate TLR7, thereby inducing the secretion of TLR7-regulated cytokines IL-12, TNF-α and IFN-α in human PBMC cells. SPR analysis confirmed that 11a could bind to TLR7 protein with an affinity of 7.06 µM. MD simulation predicted that 11a could form tight interactions with residues in the binding pocket of TLR7. Physicochemical parameters perdition and pharmacokinetic analysis indicated that 11a displayed relatively favorable drug-like properties. Considering all the results, compound 11a might be a promising lead for developing novel immunomodulatory anti-HBV agents.


Assuntos
Antivirais , Vírus da Hepatite B , Receptor 7 Toll-Like , Humanos , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Vírus da Hepatite B/efeitos dos fármacos , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/agonistas , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Replicação Viral/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Animais , Células Hep G2
2.
Br J Haematol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671576

RESUMO

The management and comprehension of relapsed or refractory multiple myeloma (RRMM) continues to pose a significant challenge. By integrating single-cell RNA sequencing (scRNA-seq) data of 15 patients with plasma cell disorders (PCDs) and proteomic data obtained from mass spectrometry-based analysis of CD138+ plasma cells (PCs) from 144 PCDs patients, we identified a state of malignant PCs characterized by high stemness score and increased proliferation originating from RRMM. This state has been designated as proliferating stem-like plasma cells (PSPCs). NUCKS1 was identified as the gene marker representing the stemness of PSPCs. Comparison of differentially expressed genes among various PC states revealed a significant elevation in LGALS1 expression in PSPCs. Survival analysis on the MMRF CoMMpass dataset and GSE24080 dataset established LGALS1 as a gene associated with unfavourable prognostic implications for multiple myeloma. Ultimately, we discovered three specific ligand-receptor pairs within the midkine (MDK) signalling pathway network that play distinct roles in facilitating efficient cellular communication between PSPCs and the surrounding microenvironment cells. These insights have the potential to contribute to the understanding of molecular mechanism and the development of therapeutic strategies involving the application of stem-like cells in RRMM treatment.

3.
Front Pharmacol ; 14: 1146960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701028

RESUMO

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes's impairment of spatial learning memory. Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35 mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines. Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aß accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3ß signaling pathway was restored by tirzepatide. Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.

4.
J Pathol Clin Res ; 9(6): 488-497, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37661840

RESUMO

Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)-lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters. We identified 146 patients (68 male, 42.9 ± 14.1 years old) with silent PIT1-lineage PitNETs. Morphology clustering suggested that tumors with large nuclei and apparent eccentricity were associated with a higher proportion of aggressiveness and a higher hazard of recurrence [hazard ratio (HR): 2.64, (95% CI, 1.06-6.55), p = 0.037]. Immunohistochemical clustering suggested that tumors with thyroid stimulating hormone (TSH) staining or all negative PIT1-lineage hormones were associated with a higher proportion of aggressiveness and a higher risk of recurrence [HR: 12.4, (95% CI, 1.60-93.5), p = 0.015]. We obtained three-tier risk profiles by combining morphological and immunohistochemical clustering. Patients with the high-risk profile presented the highest recurrence rate compared with those in the medium-risk and low-risk profiles [HR: 3.54, (95% CI, 1.40-8.93), p = 0.002]. In conclusion, digital image analysis based on cell morphology and immunohistochemical staining allows objective stratification of patients with silent PIT1-lineage tumors. Typical morphological characteristics of high-risk tumors are large tumor nuclei and high eccentricity, and typical immunostaining characteristics are TSH staining or negative staining for all PIT1-lineage hormones.

5.
J Hematol Oncol ; 15(1): 168, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434634

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. METHODS: We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression. RESULTS: A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway. CONCLUSIONS: This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Proteogenômica , Humanos , Proteômica , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Carcinogênese/genética , Transformação Celular Neoplásica , Microambiente Tumoral , Proteínas de Membrana , Proteínas ADAM , Ribonucleoproteínas , Neoplasias Pancreáticas
6.
Int J Biol Macromol ; 215: 465-476, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35714867

RESUMO

Cold plasma is a low-cost, simple and green method for starch modification. In the present study, the impact of corn starch modification by cold plasma (CP, 1, 3 and 9 min), sodium trimetaphosphate/sodium tripolyphosphate (CL, 1 %, 5 % and 10 %) and their combination were investigated. CP-pretreatment had enhancement of phosphorus content and substitution degree. Neither CP nor CL destroyed the starch granules morphology. Instead, CP induced more short-chain to better rearrange the starch during the crosslinking process, which improved the efficiency of the crosslinker in the subsequent crosslinking process. Therefore, compared with CL or CP, the thermal transition temperatures increased after CP pretreatment, while the amylose content, relative crystallinity, swelling power, and △H decreased. Meanwhile, CP-pretreatment changed the internal structure of the CL-starch so that it showed the lowest enzymatic digestibility. CP pretreatment provides a promising way to improve cross-linked starch's structure, properties, and efficiency.


Assuntos
Gases em Plasma , Amido , Amilose/química , Fenômenos Químicos , Gases em Plasma/química , Amido/química , Zea mays/química
7.
Sheng Wu Gong Cheng Xue Bao ; 38(1): 160-173, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35142127

RESUMO

The conserved hemagglutinin (HA) stem region of avian influenza virus (AIV) is an important target for designing broad-spectrum vaccines, therapeutic antibodies and diagnostic reagents. Previously, we obtained a monoclonal antibody (mAb) (5D3-1B5) which was reactive with the HA stem epitope (aa 428-452) of H7N9 subtype AIV. To systematically characterize the mAb, we determined the antibody titers, including the HA-binding IgG, hemagglutination-inhibition (HI) and virus neutralizing (VN) titers. In addition, the antigenic epitope recognized by the antibody as well as the sequence and structure of the antibody variable region (VR) were also determined. Moreover, we evaluated the cross-reactivity of the antibody with influenza virus strains of different subtypes. The results showed that the 5D3-1B5 antibody had undetectable HI and VN activities against H7N9 virus, whereas it exhibited strong reactivity with the HA protein. Using the peptide-based enzyme-linked immunosorbent assay and biopanning with a phage-displayed random peptide library, a motif with the core sequence (431W-433Y-437L) in the C-helix domain in the HA stem was identified as the epitope recognized by 5D3-1B5. Moreover, the mAb failed to react with the mutant H7N9 virus which contains mutations in the epitope. The VR of the antibody was sequenced and the complementarity determining regions in the VR of the light and heavy chains were determined. Structural modeling and molecular docking analysis of the VR verified specific binding between the antibody and the C-helix domain of the HA stem. Notably, 5D3-1B5 showed a broad cross-reactivity with influenza virus strains of different subtypes belonging to groups 1 and 2. In conclusion, 5D3-1B5 antibody is a promising candidate in terms of the development of broad-spectrum virus diagnostic reagents and therapeutic antibodies. Our findings also provided new information for understanding the epitope characteristics of the HA protein of H7N9 subtype AIV.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Animais , Anticorpos Monoclonais , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hemaglutininas , Simulação de Acoplamento Molecular
8.
Protein Expr Purif ; 192: 106046, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35007721

RESUMO

Production of broadly-reactive antibodies is critical for universal immunodiagnosis of rapidly-evolving influenza viruses. Most monoclonal antibodies (mAbs) are generated in mice using the hybridoma technology which involves labor- and time-consuming screening and low yield issues. In this study, a recombinant antibody based on a broadly-reactive mAb against the hemagglutinin (HA) stalk of H7N9 avian influenza virus was expressed in CHO cells and its biological characteristics, cross-reactivity and epitope recognition were identified. The variable genes of the parental antibody were amplified and cloned into the antibody-expressing plasmids containing the constant genes of murine IgG1. The recombinant antibody was expressed in high yield and purity in CHO cells and showed similar features to the parental antibody, including negative hemagglutination inhibition activity against H7N9 virus and high binding activity with the H7N9 HA protein. Notably, the recombinant antibody exhibited a broad reactivity with different influenza subtypes belonging to group 1 and group 2, which was associated with its recognition of a highly-conserved epitope in the stalk, as observed for the parental antibody. Our results suggest that cell-based antibody expression system can be utilized as an important alternative to the hybridoma technology for antibody production for influenza virus diagnostics.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Orthomyxoviridae/efeitos dos fármacos , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/genética , Anticorpos Antivirais/isolamento & purificação , Células CHO , Cricetinae , Cricetulus , Reações Cruzadas , Expressão Gênica , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/virologia , Camundongos , Orthomyxoviridae/classificação , Orthomyxoviridae/imunologia
9.
Sci Adv ; 7(43): eabh1022, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678055

RESUMO

To directly and quantitatively identify the transcriptional protein complexes assembled on accessible chromatin, we develop an assay for transposase-accessible chromatin using mass spectrum (ATAC-MS) based on direct transposition of biotinylated adaptors into open chromatin. Coupling with activated gene sequence information by ATAC-seq, ATAC-MS can profile the accessible chromatin-protein machinery. ATAC-MS, combined with fractionation strategies (fATAC-MS), can provide a high-resolution chromatin-transcriptional machinery atlas. ATAC-MS with a novel Tn5-dCas9 fusion protein [dCas9-targeted ATAC-MS (ctATAC-MS)] further facilitates systematic pinpointing of the transcriptional machinery at specific open chromatin regions. We used ATAC-MS and ATAC-seq to investigate transcriptional regulation during C2C12 cell differentiation and demonstrated the role of RFX1 in regulating the proliferation and differentiation of C2C12 cells. Our strategy provides a universal toolbox including ATAC-MS, fATAC-MS, and ctATAC-MS, which enables us to portray the transcriptional regulation machinery atlas in genome scale and investigate the protein-DNA complex at a specific genomic locus.

10.
Int J Biol Macromol ; 191: 821-831, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34597694

RESUMO

Plasma is a simple, effective and promising food processing technology with great potential for starch modification. Mung bean starch was subjected to ultrasound (300 W, 10, 30 and 50 min), plasma (40 V, 1, 3 and 9 min) and the synergistic treatment, as well as investigating its effects on the morphology, chain length distribution, molecular weight, crystalline structure and physicochemical properties of starch. Ultrasound and plasma treatment did not change the granule shape, but caused some corrosions on the surface, and dual treatment increased the damage degree of starch granules surface. All treatments decreased the molecular weight (Mw), amylopectin long chains and crystallinity but increased the gelatinization temperatures and enthalpy. Different from ultrasound irradiation, single plasma treatment significantly reduced the swelling power and pasting viscosities. Furthermore, dual treatment increased the thermal stability of starch paste, owing to the reinforcement effect between ultrasound and plasma. Thus, dual modification displayed an excellent ability to modify starch with specific characteristics and expand the potential application of mung bean starch in the food industry.


Assuntos
Amido/análogos & derivados , Gases em Plasma/química , Sonicação/métodos , Vigna/química , Viscosidade
11.
Virus Res ; 298: 198409, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33819520

RESUMO

H7N9 avian influenza vaccines induce high levels of non-neutralizing (nonNeu) antibodies against the haemagglutinin (HA). However, the antigenic epitopes underlying this particular antibody response are still undefined. In this study, a panel of 13 monoclonal antibodies (mAbs) against the HA protein of H7N9 virus was generated and 12 of them had no hemagglutination inhibition and virus neutralizing activities. One linear epitope in the stalk (373-TAA-375) recognized by three mAbs and one conformational epitope in the head (220Q-225S-227G) targeted by one mAb were identified using peptide-based enzyme-linked immunosorbent assay (ELISA) and biopanning of phage display random peptide library. In addition, competition ELISA revealed that the mAb targeting the head epitope strongly inhibited HA-binding of chicken nonNeu anti-H7N9 sera, whereas lower inhibition was observed for chicken neutralizing antisera, indicating the immunodominance of this epitope in the elicitation of nonNeu antibodies. Moreover, the stalk epitope is conserved among the H1-H17 subtypes and the mAb recognizing this epitope exhibited cross-reactivity with different subtypes. In conclusion, two novel nonNeu epitopes in H7N9 HA were identified, and an epitope in the head was identified as an immunodominant epitope underlying the induction of nonNeu H7N9 antibodies. Our results add new knowledge to the molecular basis for antibody immunity against H7N9 vaccines and provide useful implications for vaccine design and modification.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Hemaglutininas , Influenza Aviária/prevenção & controle
12.
Avian Dis ; 64(4): 445-450, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347548

RESUMO

Many H5 and H7 subtype avian influenza vaccines are poorly immunogenic in terms of inducing hemagglutination-inhibition (HI) antibody titers. Residue 227 (H3 numbering) in the receptor binding site in the hemagglutinin (HA) is critical for the detectability of HI antibodies induced by H5 influenza vaccines. However, whether the effect of residue 227 on immunogenicity can be generalized in different subtypes is unclear. In this study, the impact of HA residue 227 on immunogenicity of H5N1, H5N6, and H7N9 avian influenza vaccines was evaluated in chickens. Polymorphism analysis revealed that S227 is overwhelmingly dominant in HA of the H5N1 and H7N9 subtypes, whereas this amino acid is present in a small proportion of H5N6 viruses. The H5N1, H5N6, and H7N9 vaccines harboring S227 in HA induced relatively low HI titers at week 2 postimmunization (pi), and antibody titers increased at week 3 pi. S227N substitution in these vaccines consistently enhanced HI titers significantly. Another H5N6 vaccine harboring Q227 in HA elicited a robust HI antibody response, and Q227S substitution led to a significant drop of HI titers. Cross-HI testing against the wild-type and mutant viruses revealed that the amino acid at position 227 was associated with the detectability of HI titers induced by H5 and H7 avian influenza vaccines. The results indicate an important role of residue 227 in HA in immunogenicity of H5 and H7 subtype avian influenza vaccines in chickens. Our findings also provided useful information for vaccine seed virus selection and genetic engineering for immunogenicity enhancement of avian influenza vaccines.


Assuntos
Galinhas , Hemaglutininas/imunologia , Imunogenicidade da Vacina , Virus da Influenza A Subtipo H5N1/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Animais , Testes de Inibição da Hemaglutinação/veterinária , Hemaglutininas/administração & dosagem , Vacinas contra Influenza/imunologia
13.
Front Genet ; 11: 1004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193587

RESUMO

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at ERG was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N = 451), not only validating the novel ERG locus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms at ARID5B, IKZF1, CEBPE, PIP4K2A were only significantly associated with ALL susceptibility in childhood patients with no BCR-ABL fusion, while GATA3 signal exhibited its significance in adults no matter carrying BCR-ABL fusion or not. Moreover, the novel ERG SNP can be validated in pediatric patients without both BCR-ABL and ETV6-RUNX1 fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact of ERG SNP in Chinese patients.

14.
Int J Biol Macromol ; 165(Pt B): 2060-2070, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33096180

RESUMO

Naked barley grains were germinated at 25 °C for 12, 24, and 36 h, followed by hot air and infrared drying. Changes in structural, physicochemical, and functional properties of naked barley flour and starch after germination and drying were evaluated. Germinated and dried flour showed loose structure in starch granules surface. Germination and drying enhanced bulk density and water solubility of flour, while oil absorption capacity decreased. Treated barley starch showed greater water holding capacity, viscosity, and gelatinization temperature than those of native ones, and the maximum increase in water holding capacity of germinated barley was 20.25% of the native ones. Moreover, molecular weight, amylopectin long chains, and crystallinity of treated starch decreased, and the maximum decrease in the crystallinity of germinated barley was 78.36% of the native ones. Generally, germination for 24 and 36 h by infrared drying induced significant changes of flour and starch compared with hot air drying ones. Therefore, the combination of germination and infrared drying can be suggested as a promising method for modifying the properties of naked barley flour and starch to promote their application in the food industry.


Assuntos
Dessecação , Farinha/análise , Germinação , Hordeum/fisiologia , Raios Infravermelhos , Amido/química , Ar , Amilopectina/química , Varredura Diferencial de Calorimetria , Hordeum/ultraestrutura , Temperatura Alta , Peso Molecular , Óleos/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/ultraestrutura , Água , Difração de Raios X
15.
Transbound Emerg Dis ; 67(6): 3041-3048, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32602258

RESUMO

Pre-existing immunity against the conserved haemagglutinin (HA) stalk underlies the elicitation of cross-group antibody induced by natural H7N9 virus infection and immunization in humans. However, whether broadly reactive antibodies can be induced by H7N9 infection and immunization in the absence of pre-existing stalk-specific immunity is unclear. In this study, antibody response induced by H7N9 virus infection and immunization with inactivated and viral-vectored H7N9 vaccines in naïve chickens was analysed. The results showed that H7N9 infection and immunization with inactivated vaccine resulted in potent induction of haemagglutination-inhibition (HI), virus neutralization (VN) and HA-binding antibodies, whereas Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and VN titres but high levels of HA-binding antibody. In addition, H7N9 infection and immunization induced stalk-specific antibodies in naïve chickens and these antibodies recognized different epitopes in the stalk. Virus infection and immunization with inactivated vaccine elicited antibodies cross-reactive with both group 1 and group 2 HAs, while antibodies induced by NDV-H7N9 vaccination showed a narrower cross-reactivity within group 2. Moreover, only homologous neutralizing activity of the sera against H7N9 virus was observed, and cross-binding antibodies did not show heterosubtypic neutralizing activity. Our results indicated that cross-group binding but non-neutralizing antibodies primarily targeting the stalk can be induced by natural H7N9 infection and immunization with inactivated vaccine in naïve chickens. This suggests that at least in a naïve chicken model, pre-existing stalk-specific immunity is not required for induction of broadly reactive antibodies. Additionally, H7N9-based immunogens may be explored as vaccine candidates or as a prime component to induce broadly protective influenza immunity.


Assuntos
Anticorpos Antivirais/imunologia , Galinhas , Imunização/veterinária , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Animais , Formação de Anticorpos , Reações Cruzadas , Influenza Aviária/imunologia , Doenças das Aves Domésticas/imunologia , Vacinas de Produtos Inativados/administração & dosagem
16.
Front Vet Sci ; 6: 482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31998763

RESUMO

Hemagglutination inhibition (HI) and virus neutralization antibody (nAb) do not always correlate with the protection of H7 avian influenza vaccines in mammals and humans. The contribution of different classes of antibodies induced by H7N9 vaccines to protection is poorly characterized in chickens. In this study, antibody responses induced by both inactivated and viral-vectored H7N9 vaccines in chickens were dissected. Chickens immunized with inactivated H7N9 vaccine showed 50% seroconversion rate and low HI and nAb titers at week 3 post immunization. However, inactivated H7N9 vaccine elicited 100% seroconversion rate in terms of high levels of HA-binding IgG antibody determined by ELISA. Despite inducing low levels of nAb, inactivated H7N9 vaccine conferred full protection against H7N9 challenge in chickens and markedly inhibited virus shedding. Similarly, Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and nAb titers but high level of IgG antibody against H7N9 virus. In addition, NDV-H7N9 vaccine also provided complete protection against H7N9 challenge. Chicken antisera had a high IgG/VN ratio, indicating that a larger proportion of serum antibodies were non-neutralizing antibody (non-nAb). More importantly, passive transfer challenge experiment showed that non-neutralizing antisera provided partial protection (37.5%) of chickens against H7N9 challenge, without significant difference from that provided by neutralizing antisera. In conclusion, our results suggest that antibodies measured by the traditional HI and virus neutralization assays do not correlate with the protection of inactivated and viral-vectored H7N9 vaccines in chickens, and HA-binding non-nAb also contributes to the protection against H7N9 infection. Total binding antibody can be used as a key correlate to the protection of H7N9 vaccine.

18.
J Alzheimers Dis ; 52(3): 899-911, 2016 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-27060945

RESUMO

Epidemiological data imply links between the increasing incidences of Alzheimer's disease (AD) and type 2 diabetes mellitus. In this study, an AD rat model was established by combining treatments with intracerebroventricular streptozotocin (icv-STZ) and subcutaneous D-galactose, and the effects of curcumin on depressing AD-like symptoms were investigated. In the AD model group, rats were treated with icv-STZ in each hippocampus with 3.0 mg/kg of bodyweight once and then were subcutaneously injected with D-galactose daily (125 mg/kg of bodyweight) for 7 weeks. In the curcumin-protective group, after icv-STZ treatment, rats were treated with D-galactose (the same as in the AD model group) and intraperitoneally injected with curcumin daily (10 mg/kg of bodyweight) for 7 weeks. Vehicle-treated rats were treated as control. Compared with the vehicle control, the amount of protein carbonylation and glutathione in liver, as well as malondialdehyde in serum, were upregulated but glutathione peroxidase activity in blood was downregulated in the AD model group. The shuttle index and locomotor activity of rats in the AD model group were decreased compared with the vehicle control group. Furthermore, AD model rats showed neuronal damage and neuron loss with formation of amyloid-like substances and neurofibrillary tangles, and the levels of both ß-cleavage of AßPP and phosphorylation of tau (Ser396) were significantly increased compared with the vehicle control group. Notably, compared with the AD model group, oxidative stress was decreased and the abilities of active avoidance and locomotor activity were improved, as well as attenuated neurodegeneration, in the curcumin-protective group. These results imply the applications of this animal model for AD research and of curcumin in the treatment of AD.


Assuntos
Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Curcumina/uso terapêutico , Galactose/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Estreptozocina/toxicidade , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Modelos Animais de Doenças , Galactose/administração & dosagem , Glutationa/metabolismo , Hipocampo/metabolismo , Injeções Intraventriculares/métodos , Injeções Subcutâneas/métodos , Masculino , Malondialdeído/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Presenilina-1/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estreptozocina/administração & dosagem , Proteínas tau/metabolismo
19.
Wei Sheng Wu Xue Bao ; 51(10): 1318-25, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22233052

RESUMO

OBJECTIVE: To exploit resources of purple sulfur bacteria in China and further investigate its response mechanism to ecological environment of mangrove. METHODS: Repeated agar shake dilution method, microscope techniques, UV-Vis absorption spectra, thin layer chromatography, HPLC and MS were used. RESULTS: We isolated a purple sulfur bacterium, designated as strain YL28, from a intertidal sediment sample collected from inshore mangrove near Luoyang Bridge of Quanzhou city, Fujian Province of China. Cells were ovoid to rod shaped, 0.5 microm - 1 microm x 2 microm - 3 microm. Color of cell suspensions was reddish-brown. It possessed vesicular intracytoplasmic membrane structures, contained rhodopin and phytylated bacteriochlorophyll a as well as the other two novel bacteriochlorophyll a intermediates. The optimum growth was at 2% - 3.5% NaCl, pH 5.7 - 6.7 and 20 degrees C - 35 degrees C. Photoautotrophically growth anaerobically in the light with sulphide, sulphur, thiosulfate, sulfite as electron donor. Globules of S(0) distributed inside the cells. Photoheterotrophic growth with various organic substrates, especially citrate, glucose, sucrose, fructose and propanol in the presence of sulfide. Nitrogen sources: ammonium salts, N2, urea, glutamate, nitrate and nitrite. Vitamins were not required. Qualitative assessment of IC50 values of chloromycetin, cefazolin, benzene, hydroxy biphenyl, enrofloxacin, acetamiprid, mercuric chloride and cadmium chloride were 70, 100, 20, 20, 3, 170, 5 mg/L and 25 mg/L, respectively. CONCLUSION: Based on phenotype characteristics and 16S rRNA gene sequence similarity of 99% to M. gracile, strain YL28 was identified as novel isolate of M. gracile despite its different physiological characteristics with respect to the species of M. gracile. The organism is possessed of slightly acid tolerance, higher amount of carotenoid of rhodopin and tolerance towards certain antibiotics, pesticide as well as heavy metals.


Assuntos
Carotenoides/biossíntese , Chromatiaceae/isolamento & purificação , Chromatiaceae/metabolismo , Água do Mar/microbiologia , Bacterioclorofila A/metabolismo , Chromatiaceae/classificação , Chromatiaceae/genética , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética
20.
Wei Sheng Wu Xue Bao ; 49(9): 1146-51, 2009 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-20030050

RESUMO

Anoxygenic phototrophic bacteria have evolved highly efficient systems-membrane-located pigment-protein complexes which can convert sunlight into chemical energy that they can use and also benefit other organisms. More and more attentions have been paid to pigment-protein complexes of anoxygenic phototrophic bacteria in recent years. We summarized the current opinions in the pigment-protein complexes from anoxygenic phototrophic bacteria, including their chemical compositions, crystal structures and functions, homology of protein sequence. In particular, we depicted the novel light-harvesting complexes namely LH3 and LH4. The problems and prospects about the pigment-protein complexes have also been addressed in this review.


Assuntos
Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Oxigênio/metabolismo , Fotossíntese , Pigmentos Biológicos/metabolismo , Anaerobiose , Bactérias/química , Bactérias/efeitos da radiação , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Pigmentos Biológicos/química
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