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1.
Cancer Sci ; 114(2): 533-545, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36380570

RESUMO

Tuftelin (TUFT1) is highly expressed in various tumor types and promotes tumor growth and metastasis by activating AKT and other core signaling pathways. However, the effects of post-translational modifications of TUFT1 on its oncogenic function remain unexplored. In this study, we found that TUFT1 was SUMOylated at K79. SUMOylation deficiency significantly impaired the ability of TUFT1 to promote the proliferation, migration, and invasion of gastric cancer (GC) cells by blocking AKT/mTOR signaling pathway activation. SUMOylation of TUFT1 is mediated by the E3 SUMO ligase tripartite motif-containing protein 27 (TRIM27), and these two proteins regulate the malignant behavior of GC cells and AKT activation in the same pathway. TUFT1 binds to TRIM27 through its N-terminus, and decreased binding affinity of TUFT1 to TRIM27 significantly impairs its oncogenic effect. In addition, data collected from GC clinical samples indicated that the combined detection of TUFT1 and TRIM27 expression reflected tumor malignancy and patient survival with higher precision. In addition, we proved that SUMOylated TUFT1 is not only an upstream signal for AKT activation but also directly activates mTOR by forming a complex with Rab GTPase activating protein 1, which further inhibits Rab GTPases and promotes the perinuclear accumulation of mTORC1. Altogether, these data indicate that SUMOylated TUFT1 is the active form that affects GC progression through the AKT/mTOR signaling pathway and might be a promising therapeutic target or biomarker for GC progression.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sumoilação , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Movimento Celular
2.
Anal Chem ; 94(28): 10091-10100, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35737958

RESUMO

Radioactive U(VI) in nuclear wastewater is a global environmental pollutant that poses a great threat to human health. Therefore, it is of great significance to develop a U(VI) sensor with desirable sensitivity and selectivity. Inspired by electron-donating group modification for enhancement of binding affinity toward U(VI), we report an amine group functionalization of UiO-66-NH2, using a low-cost, environmentally friendly, and low-temperature NH3 plasma technique as a fluorescence switching nanoprobe for highly sensitive and selective detection of U(VI). The resulting amine-functionalized UiO-66-NH2 (LTP@UiO-66-NH2) shows dramatically enhanced fluorescence emission and selective sensitivity for U(VI) on the basis of the quenching effect. The quenching efficiency increases from 58 to 80% with the same U(VI) concentration (17.63 µM) after NH3 plasma functionalization. As a result, the LTP@UiO-66-NH2 has the best Ksv (1.81 × 105 M-1, 298 K) and among the lowest LODs (0.08 µM, 19.04 ppb) compared with those reported in the literature. Intraday and interday precision and application in real environment experiments indicate stable and accurate U(VI) detection performance. Fluorescence lifetime and temperature-dependent detection experiments reveal that the quenching mechanism belongs to the static quenching interaction. The highly selective fluorescence detection is attributed to the selective binding of U(VI) by the rich functionalized amine groups of LTP@UiO-66-NH2. This work provides an efficient fluorescence probe for highly sensitive U(VI) detection in water, and a new strategy of tailored plasma functionalization for developing a practical MOF sensor platform for enhanced fluorescence emission, sensitivity, and selectivity for detecting trace amounts of radioactive species in the environment.


Assuntos
Compostos Organometálicos , Ácidos Ftálicos , Aminas , Humanos , Estruturas Metalorgânicas , Água
3.
Chemistry ; 24(32): 8205-8216, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29528515

RESUMO

A highly convergent and efficient strategy was developed for the chemical synthesis of complex oligosaccharides of Streptococcus pneumoniae type 3 capsular polysaccharides that contain multiple glucuronic acid units. Once the oligoglucosides were efficiently and stereoselectively assembled, the designated glucose units were regioselectively oxidized to glucuronic acid in one step at the final synthetic stage, which helped avoid difficult glycosylations that involved glucuronic acid. The target oligosaccharides had a free amino group at the reducing terminus and varied caps at the non-reducing terminus to enable further modification and structure-activity relationship studies. Immunological evaluations of the oligosaccharide-tetanus toxoid conjugates showed that they elicited robust T-cell-dependent immunoglobulin G antibody responses and that the sugar chain length had a major impact on their immunological properties. In particular, the penta- and hexasaccharides were identified as promising antigens for vaccine development.


Assuntos
Cápsulas Bacterianas/química , Imunoglobulina G/imunologia , Oligossacarídeos/síntese química , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/química , Toxoide Tetânico , Glicosilação , Oligossacarídeos/química , Polissacarídeos Bacterianos/química , Sorogrupo
4.
J Org Chem ; 82(23): 12085-12096, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29112822

RESUMO

A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. The same tetrasaccharide was also coupled with MPLA at the 1-O-position. Immunological activities of the two synthetic conjugates were evaluated in mice and compared. Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. Moreover, the 6'-N-conjugate afforded antibody titers much higher than those of the 1-O-conjugate. These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines.


Assuntos
Adjuvantes Imunológicos/síntese química , Antituberculosos/síntese química , Lipídeo A/análogos & derivados , Lipopolissacarídeos/química , Vacinas/química , Adjuvantes Imunológicos/química , Antituberculosos/química , Lipídeo A/química , Estrutura Molecular
5.
J Org Chem ; 80(20): 10060-75, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26375482

RESUMO

Lipoarabinomannan (LAM) is one of the major constituents of the Mycobacterium tuberculosis cell wall and an attractive molecular scaffold for antituberculosis drug and vaccine development. In this paper, a convergent strategy was developed for the synthesis of LAM oligosaccharides with an α-1,2-linked dimannopyranose cap at the nonreducing end. The strategy was highlighted by efficient coupling of separately prepared nonreducing end and reducing end oligosaccharides. Glycosylations were mainly achieved with thioglycoside donors, which gave excellent yields and stereoselectivity even for reactions between complex oligosaccharides. The strategy was utilized to successfully synthesize tetra-, hepta-, and undecasaccharides of LAM from d-arabinose in 10, 15, and 14 longest linear steps and 7.84, 7.50, and 2.59% overall yields, respectively. The resultant oligosaccharides with a free amino group at their reducing end were effectively conjugated with carrier proteins, including bovine serum albumin and keyhole limpet hemocyanin (KLH), via a bifunctional linker. Preliminary immunological studies on the KLH conjugates revealed that they could elicit robust antibody responses in mice and that the antigen structure had some influence on their immunological property, thus verifying the potential of the oligosaccharides for vaccine development and other immunological studies.


Assuntos
Adjuvantes Imunológicos/síntese química , Antituberculosos/síntese química , Parede Celular/química , Lipopolissacarídeos/síntese química , Mycobacterium tuberculosis/química , Oligossacarídeos/síntese química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/metabolismo , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Parede Celular/imunologia , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Mycobacterium tuberculosis/imunologia , Oligossacarídeos/química , Oligossacarídeos/farmacologia
6.
RSC Adv ; 14(22): 15656-15663, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38746835

RESUMO

Carbon-based catalysts catalyze methane decomposition to produce hydrogen is a very attractive technical route. Carbon black in carbon-based catalysts has the advantages of high catalytic activity, good stability and better tolerance to toxic impurities such as sulphur in the feedstock, which has become a hot topic of research for many scientists. In this work, the effect of heat treatment on the structural and surface properties of carbon blacks and their catalytic performance in hydrogen production from methane decomposition was investigated. A commercial carbon blacks N110 was selected to heat treatment with nitrogen or carbon dioxide atmosphere at 850 °C, respectively. The Raman spectrums indicated that the graphitization degree of modified carbon under two atmospheres were promoted with the treatment time increasing. BET results revealed that the specific surface area of the carbon black treated under carbon dioxide increased, while the specific surface area was unchanged for that of the carbon black treated under nitrogen. The catalytic test of the two modified carbon blacks for methane decomposition exhibited the almost same activity, which meant that the graphitization degree of carbon black is the key factor for methane decomposition rather than the specific surface area. It was suggested that highly graphitized carbon black could be used as the potential catalysts for hydrogen production from methane decomposition.

7.
Front Genet ; 15: 1410145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957810

RESUMO

Background: Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS. Methods: RNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of SLC25A4 was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells. Results: In all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both SLC25A4 transcript and protein expression were significantly reduced in OS, and GSEA suggested that SLC25A4 was associated with cell cycle, apoptosis and inflammation. SLC25A4-overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis. Conclusion: SLC25A4 was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of SLC25A4 expression levels may be beneficial in OS treatment.

8.
J Inflamm Res ; 17: 5783-5800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224661

RESUMO

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.

9.
Materials (Basel) ; 16(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37374546

RESUMO

The lithium-sulfur (Li-S) battery is considered to be one of the attractive candidates for breaking the limit of specific energy of lithium-ion batteries and has the potential to conquer the related energy storage market due to its advantages of low-cost, high-energy density, high theoretical specific energy, and environmental friendliness issues. However, the substantial decrease in the performance of Li-S batteries at low temperatures has presented a major barrier to extensive application. To this end, we have introduced the underlying mechanism of Li-S batteries in detail, and further concentrated on the challenges and progress of Li-S batteries working at low temperatures in this review. Additionally, the strategies to improve the low-temperature performance of Li-S batteries have also been summarized from the four perspectives, such as electrolyte, cathode, anode, and diaphragm. This review will provide a critical insight into enhancing the feasibility of Li-S batteries in low-temperature environments and facilitating their commercialization.

10.
J Asthma Allergy ; 16: 397-410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37081905

RESUMO

Background: Children are the age group with the highest prevalence of allergy diseases. There is currently a lack of knowledge regarding monosensitization and polysensitization characteristics in children. In this study, we investigated the characteristics and differences between monosensitization and polysensitization in children in Weifang, eastern China. Objective: To demonstrate the basic features of monosensitization and polysensitization in children. To explore the inherent and clinical parameter differences between monosensitized and polysensitized children. Material and Methods: A total of 6030 individuals with a physician-determined need for allergy testing were tested for 15 common allergens, including 9 aeroallergens and 6 food allergens. A total of 938 allergen-positive children aged 1 month to 18 years were eventually included in this analysis. Complete blood count results from the same time as the allergen test were derived from the computerized medical records. Intrinsic features such as age, gender, sIgE, T-IgE, and clinical parameters such as eosinophil percentage, eosinophil count, basophil percentage, and basophil count were compared. Results: The results showed that dust mite-related allergens, mould-related allergens, and tree and grass pollen-related allergens were the most prevalent allergens among monosensitized children. Additionally, the results of the combined pattern of polysensitive childhood allergens indicate the most common two allergens that were present together included dust mites and mould-related allergens, dust mite and Artemisia pollens, and dust mite and Humulus scandens pollens. Polysensitization can result in higher sIgE, T-IgE and eosinophil levels. Conclusion: In conclusion, we provide a basic overview of allergens in monosensitized and polysensitized children. These findings provide new insight into the management of allergic diseases, particularly from the standpoint of polysensitization.

11.
RSC Adv ; 12(27): 17490-17497, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35765424

RESUMO

Spinel oxides (AB2O4) have been widely studied as catalysts for methane combustion. Increasing attention was focused on the catalysis properties of the [B2O3] octahedron; however, the role of the [AO] tetrahedron in the catalytic activity was seldom discussed. Herein, a series of (CuO) x -CuCo2O4 (x = 0, 0.1, 0.2) composite oxides were synthesized by a solvothermal method. The structure, morphology, and physicochemical properties of the as-synthesized samples were characterized by the XRD, SEM, BET, and XPS techniques. The results of the catalytic activity tests showed that the coexistence of CuO with CuCo2O4 can improve the catalytic activity. The XPS results demonstrated that there were remarkable Cu+ ions present in the composite oxides, which can cause increases in the number of oxygen vacancies on the surface of the catalysts. In addition, the redox of Cu+ and Cu2+ may improve the oxygen exchange capacity for methane oxidation.

12.
J Asthma Allergy ; 15: 1179-1194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059920

RESUMO

Background: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study. Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma. Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs. Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma. Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.

13.
Int J Biol Macromol ; 206: 661-669, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35248605

RESUMO

A series of poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) composites containing different types of multi-walled carbon nanotubes (CNTs) such as hydroxyl and carboxyl-functionalized CNTs were fabricated using the melt blending method. The multifunctional epoxy oligomer (ADR) was selected as a chain extender in order to enhance the compatibility between PBAT and PLA. It was revealed that the addition of ADR could induce CNTs-OH to locate at the PLA/PBAT interface. But the inhibition effect of CNTs-COOH on chain extension reaction in PLA/PBAT blend system led to a decrease in the interaction force between PLA and PBAT owing to the high efficiency of the reaction between CNTs-COOH and ADR. The ε' of PLA/PBAT/4CNTs-OH composite was greater than that of PLA/PBAT/4CNTs-COOH composite because of the strong interaction between fillers and polymer matrix in PLA/PBAT/4CNTs-OH composite. The PLA/PBAT/4CNTs-OH composite showed a high ε' (24.9) and a low tan δ (0.23), respectively. The adjacent CNTs-OH could act as assemble microcapacitors electrodes and the polymer acted as a dielectric to, which greatly increased the interfacial polarization. The PLA/PBAT/4CNTs-OH composite has excellent mechanical and dielectric properties.


Assuntos
Nanotubos de Carbono , Adipatos , Alcenos , Radical Hidroxila , Ácidos Ftálicos , Poliésteres , Polímeros
14.
Int J Biol Macromol ; 221: 573-584, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36087754

RESUMO

In order to synchronously improve mechanical and flame retardant properties of polylactide/poly(butylene adipate-co-terephthalate) (PLA/PBAT) composites, a series of multifunctional composites containing multi-walled carbon nanotubes (CNTs), ammonium polyphosphate (APP) and a commercial multifunctional epoxy oligomer (MEO) as chain extender were prepared via melt blending. The results show that the optimal flame retardant properties of PLA5-PBAT5/10A/6C composite containing 6 % CNTs and 10 wt% APP, presented the limited oxygen index reached 28.3 % and exhibited a decrease in peak heat release rate (pHRR) and total heat release (THR) to 368 kJ/m2 and 72 MJ/m2, respectively because of the co-continuous phase, CNTs network and condensed effect of APP. Meanwhile, the construction of co-continuous phases endows PLA5-PBAT5 with better mechanical compared to PLA8-PBAT2 composites. The elongation at break reaches (245.9 %) and notched impact strength (16.5 kJ/m2) of PLA5-PBAT5/10A/6C were higher than the PLA8-PBAT2/10A/6C by 16.0 and 283.7 %.


Assuntos
Compostos de Amônio , Retardadores de Chama , Nanotubos de Carbono , Polifosfatos , Poliésteres , Adipatos
15.
Vaccines (Basel) ; 9(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572233

RESUMO

Group A streptococcal C5a peptidase (ScpA) is a highly conserved surface virulence factor present on group A streptococcus (GAS) cell surfaces. It has attracted much more attention as a promising antigenic target for GAS vaccine development due to its high antigenicity to stimulate specific and immunoprotective antibodies. In this study, a series of segments of ScpA were rationally designed according to the functional domains described in its crystal structure, efficiently prepared and immunologically evaluated so as to assess their potential as antigens for the development of subunit vaccines. Immunological studies revealed that Fn, Fn2, and rsScpA193 proteins were promising antigen candidates worthy for further exploration. In addition, the potential of Fn and Fn2 as carrier proteins to formulate effective glycoconjugate vaccine was also investigated.

16.
J Colloid Interface Sci ; 580: 345-353, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32688125

RESUMO

In this study, ammonium thiocyanate functionalized graphene oxide (ATGO)-supported nanoscale zero-valent iron composite (ATGO-nZVI) employed to extract Cr(VI) from aqueous solution, was successfully synthesized by chemical oxidative polymerization and sodium borohydride reduction method. Characteristics of X-ray diffraction and high-resolution transmission electron microscopy confirmed the high disperse and activity of nZVI after supported by ATGO. Batch experiments showed that the removal efficiency of ATGO-nZVI was higher than that of bared nZVI and ATGO. Furthermore, the stability of ATGO-nZVI composite was higher than that of nZVI, which was proved by the Tafel polarization curves. Dynamic experiments suggested that the removal process was confirmed to be in agreement with not only the pseudo-second-order model for adsorption but also Langmuir-Hinshelwood first-order model for reduction process, which revealed that the removal of Cr(VI) by ATGO-nZVI composite was dominated by chemical surface-limiting step. Considering the experiments and characterization, the removal mechanism containing rapid adsorption of Cr(VI) onto the ATGO-nZVI surface and reduction by nZVI was clarified. The above results suggested that ATGO-nZVI would become a promising remediation material for Cr(VI) pollution cleanup.

17.
ACS Infect Dis ; 6(2): 281-290, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31872763

RESUMO

Group A streptococcus (GAS) is one of the common Gram-positive pathogenic bacteria accounting for a variety of infectious diseases. Currently, there is no commercial vaccine for GAS. To develop efficient GAS vaccines, synthetic tri-, hexa-, and nonasaccharides of a conserved group A carbohydrate (GAC) were conjugated with an inactive mutant of group A streptococcal C5a peptidase (ScpA), ScpA193, to create bivalent conjugate vaccines, which were compared with the corresponding CRM197 and TT conjugates. Systematic evaluations of these semisynthetic conjugates demonstrated that they could induce robust and comparable T-cell-dependent immune responses in mice. It was further disclosed that antibodies provoked by the ScpA193 conjugates, especially that of hexa- and nonasaccharides, could recognize and bind to GAS cells and mediate GAS opsonophagocytosis in vitro. In vivo evaluations of the hexa- and nonasaccharide-ScpA193 conjugates using a mouse model revealed that immunizing mice with especially the latter conjugate could effectively protect the animals from GAS challenges and GAS-induced pulmonary damage and significantly increase animal survival. Further in vitro studies suggested that the two ScpA193 conjugates could function through activating CD4+ T cells and promoting helper T cells (Th) to differentiate into antigen-specific Th1 and Th2 cells. In conclusion, the nonasaccharide-ScpA193 conjugate was identified as a particularly promising GAS vaccine candidate that is worthy of further investigation and development.


Assuntos
Adesinas Bacterianas/metabolismo , Endopeptidases/metabolismo , Oligossacarídeos/metabolismo , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/enzimologia , Adesinas Bacterianas/imunologia , Animais , Anticorpos Antibacterianos/sangue , Linfócitos T CD4-Positivos/imunologia , Endopeptidases/imunologia , Feminino , Glicoconjugados/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Oligossacarídeos/imunologia , Células Th1/imunologia , Células Th2/imunologia , Vacinas Conjugadas/imunologia
18.
ACS Infect Dis ; 6(8): 2181-2191, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32687317

RESUMO

Pneumolysin (Ply), pneumococcal surface protein A (PspA), and pneumococcal surface adhesin A (PsaA) are promising cell surface protein antigen targets for Streptococcus pneumoniae (Spn) vaccine development. Herein, we designed and recombined two fusion proteins, named YAPO and YAPL, which contained the main antigenic epitopes of Ply, PspA, and PsaA. In-depth immunological evaluations revealed that YAPO and YAPL had strong immunocompetence to be well-qualified potential carrier proteins. To verify this possibility, a serotype 3 Spn (ST3) CPS pentasaccharide was conjugated to each fusion protein to generate the resultant glycoconjugates. Immunological studies in mice revealed that, as compared with TT conjugate, YAPO and YAPL conjugates provoked robust T-cell dependent immune responses that could provide better recognition, in vitro efficient opsonophagocytosis, and in vivo effective protection against various serotypes of Spn. Collectively, YAPO and YAPL were identified as immunopotentiating carriers that could help convert immunologically inactive ST3 pentasaccharide into a T cell-dependent antigen and provide efficient and broad spectrum of immunoprotection coverage so as to formulate functional glycoconjugate vaccines against Spn infections.


Assuntos
Proteínas de Transporte , Infecções Pneumocócicas , Animais , Glicoconjugados , Camundongos , Camundongos Endogâmicos BALB C , Infecções Pneumocócicas/prevenção & controle , Proteínas Recombinantes de Fusão/genética
19.
ACS Infect Dis ; 5(8): 1423-1432, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31126171

RESUMO

Streptococcus pneumoniae serotype 3 (ST3) is one of the main pneumococcal strains that can cause severe invasive diseases, but its current vaccines are relatively inefficient. To develop more effective ST3 vaccines, tetanus toxoid (TT) conjugates of the synthetic penta-, hexa-, hepta-, and octasaccharide analogs of ST3 capsular polysaccharide (CPS) were systematically studied. These conjugates, especially those of penta- and hexasaccharides, were demonstrated to induce extremely robust T cell-dependent immune responses in mouse. Various studies also revealed that the induced antibodies could recognize ST3 CPS and mediate in vitro opsonophagocytic killing of ST3 cells. It was proved ultimately that immunization with the hexasaccharide-TT conjugate could completely protect mice from ST3-caused infection and lung damage and significantly elongate mouse survival. It was proposed that this conjugate functions through the help of CD4+ T cells and via promoting Th cell differentiation into carbohydrate antigen-specific Th2 cells to establish humoral immunity. In conclusion, ST3 CPS hexasaccharide-TT was identified as a particularly promising ST3 vaccine candidate worthy of further investigation and development.


Assuntos
Anticorpos Antibacterianos/sangue , Linfócitos T CD4-Positivos/imunologia , Glicoconjugados/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pneumoniae/imunologia , Animais , Feminino , Glicoconjugados/administração & dosagem , Glicoconjugados/química , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções Pneumocócicas/imunologia , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Sorogrupo , Vacinas Estreptocócicas/administração & dosagem , Vacinas Estreptocócicas/síntese química , Toxoide Tetânico/imunologia , Células Th1/imunologia
20.
J Colloid Interface Sci ; 552: 735-743, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176920

RESUMO

In this study, chitosan (CS) loading well-dispersed nanoscale zero-valent iron (NZVI/CS) was successfully prepared via the liquid-phase reduction method. Characterizations of the NZVI/CS with high-resolution transmission electron microscopy and X-ray diffraction suggested that the as-prepared NZVI/CS comprised numerous dispersed Fe0 nanoparticles. Synergistic adsorption and reduction occurred during the removal process based on X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Influence of pH, contract time and temperature on U(VI) removal were investigated. The high removal capacity and rapid removal kinetics were predominately ascribed to the existence of well-distributed NZVI, which could rapidly reduce U(VI) into U(IV). The removal process could be better depicted by the Langmuir isotherm model and the pseudo-second-order kinetic model. The thermodynamic parameters showed that the removal process was exothermic. These findings indicate that the synthesized NZVI/CS composites have potential application for the removal of U(VI) from the sewage water.

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