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1.
Biomaterials ; 278: 121164, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34601196

RESUMO

Bacterial infection treatment and subsequent tissue rebuilding are the main tasks of biomaterial research. To endow implants with antibacterial activity and biological functions, the material systems are usually very complicated and ineffective. Recently, the concept of photobiomodulation (PBM), or low-level laser therapy (LLLT), has attracted increasing attention in tissue repair applications but still has not obtained wide acceptance. Because of the same laser resource, PBM could simultaneously work with 660 nm laser triggered photodynamic therapy (PDT), which will significantly simplify the material system and achieve the multiple functions of antibacterial activity and biological modulation effects. Herein, we attempt to validate the effectiveness of PBM and combine PBM with a PDT-based material system. A catechol motif-modified methacrylated gelatin containing photosensitizer Chlorin e6-loaded mesoporous polydopamine nanoparticles was fabricated (GelMAc/MPDA@Ce6). This hydrogel could be tightly adhered to titanium surfaces to serve as surface coating materials or directly used as dressings. Because of the 660 nm laser-triggered ROS generation property of Ce6, GelMAc/MPDA@Ce6 exhibited a remarkable and rapid antibacterial activity when the laser power was 1 W cm-2. After bacterial elimination, when the power was adjusted to 100 mW cm-2, daily irradiation brought an excellent PBM effect: the fibroblast activation was realized to accelerate wound repair. According to our in vitro and in vivo results, the fabricated hydrogel coating possessed both antibacterial activity and fibroblast activation ability only by adjusting the power of laser irradiation, which will greatly strengthen the confidence of using PBM in broader fields and give a good example to combine PBM with traditional biomaterial design.

2.
Small ; : e2102907, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665526

RESUMO

Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting pro-inflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO2 nanotubes. Then synthesized CaO2 nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H2 O2 release from CaO2 NPs. The potential cytotoxicity of CaO2 NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions.

3.
Biotechnol J ; : e2100335, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599551

RESUMO

Foodborne pathogen contamination is a major safety issue for many foods and is causing concern worldwide. In this study, a detection system based on magnetic separation, multiplex PCR (MPCR) and capillary electrophoresis (CE) technologies was developed for the simultaneous detection of four foodborne pathogens. Magnetic separation technology is used to rapidly capture pathogenic bacteria in food samples, and then a combination of MPCR and CE can be used to greatly increase detection sensitivity. Our detection limit for bacterial DNA reached 10-5 ∼ 10-7  ng/µL and in our analysis of mocked food samples, our assay showed good sensitivity for bacterial detection ranging from 101 to 105 CFU/mL with excellent specificity. Compared to similar detection methodologies, our technique avoids the need for time-consuming enrichment cultures, is more sensitive and can be used to assay simultaneously four foodborne pathogens. This article is protected by copyright. All rights reserved.

4.
Appl Opt ; 60(26): 8088-8096, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613071

RESUMO

Electromagnetic (EM) metasurface mantles afford an alternative avenue, allowing for the possibility of rendering arbitrary-shape objects unobservable. But the available mechanisms either depend on the states of polarization or the azimuth of wave incidence, or cannot dynamically manipulate cloaking responses without altering the structures. Herein, a three-dimensional closed-ring-based metasurface carpet cloak involving Ge2Sb2Te5 that circumvents current drawbacks of metasurface structures is proposed. By judiciously designing meta-atoms on the external surface of a spherical object, the scattered wavefront, including the distributions of EM fields and polarizations, can be reconstructed, resembling what is deflected from a flat plane. Enabled by the perfectly symmetric distribution of meta-atoms, the carpet cloak is demonstrated to work well under arbitrary states of polarization and arbitrary azimuthal angles of incident light. Meanwhile, by converting Ge2Sb2Te5 from the amorphous to crystalline state, the designed scheme is empowered with the ability to switch "ON" and "OFF" of stealth states. Furthermore, the unique design achieves invisibility over ±20∘ angular span in the mid-infrared range from 8800 to 9450 nm. The validated recipe empowers robust steps forward to achieve full-polarization, full-azimuth operation, and switchable cloaking in the real-world, showing great potential applications in stealth, camouflage, and illusion fields.

5.
Oncogenesis ; 10(10): 66, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611125

RESUMO

Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including CD44 + / ALDH2 + /ALDH6A1 + breast cancer stem cells (BCSCs), which had a copy-number variants profile similar to that of normal breast tissue. Importantly, BCSCs existed only in primary tumors and evolved into metastatic clusters infiltrating into lymph nodes. Furthermore, transcriptome data suggested that NECTIN2-TIGIT-mediated interactions between metastatic breast cancer cells and tumor microenvironment (TME) cells, which promoted immune escape and lymph node metastasis. This study is the first to delineate the transcriptome profile of breast cancer lymph node metastasis using single-cell RNA sequencing. Our findings offer novel insights into the mechanisms underlying breast cancer metastasis and have implications in developing novel therapies to inhibit the initiation of breast cancer metastasis.

6.
Planta ; 254(5): 102, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34671899

RESUMO

MAIN CONCLUSION: Salt and alkali stress affected the photosynthetic characteristics of Chinese cabbages. A salt-tolerant cultivar maintained its tolerance by ensuring the high ability of photosynthesis. The synthesis of organic acids and carbohydrates in leaves played important roles in improving the photosynthetic capacity of alkali-tolerant plants. Soil salinization has become an increasingly serious ecological problem, which limits the quality and yield of crops. As an important economic vegetable in winter, however, little is known about the response of Chinese cabbage to salt, alkali and salt-alkali stress in photosynthetic characteristics and chloroplast ultrastructure. Thus, two Chinese cabbage cultivars, 'Qinghua' (salt-tolerant-alkali-sensitive) and 'Biyu' (salt-sensitive-alkali-tolerant) were investigated under stresses to clarify the similarities and differences between salt tolerance and alkali tolerance pathways in Chinese cabbage. We found that the root of Qinghua, the leaf ultrastructure and net photosynthetic rate (Pn), stomatal conductance (Gs), water use efficiency (WUE), maximum photochemical quantum yield of PSII (Fv/Fm) and nonphotochemical quenching (NPQ) were not affected by salt stress. However, Biyu was seriously affected under salt stress. Its growth indexes decreased by between 60 and 30% compared with the control and the photosynthetic indexes were also seriously affected under salt stress. This indicated that the salt-tolerant cultivar Qinghua improved the photosynthetic fluorescence ability to promote the synthesis of organic matter resulting in salt tolerance. In contrast, under alkali treatment, the root of Biyu was affected by alkali stress, but could still maintain good growth, and root and leaf structure were not seriously affected and could maintain the normal operations. Biyu improved its tolerance by improving the water use efficiency, regulating the synthesis of organic acids and carbohydrates, ensuring the synthesis of organic matter and ensured the normal growth of the plant.

7.
J Anim Ecol ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668568

RESUMO

Morphological trait-matching and species abundance are thought to be the main factors affecting the frequency and strength of mutualistic interactions. However, the relative importance of trait-matching and species abundance in shaping species interactions across environmental gradients remains poorly understood, especially for plant-insect mutualisms involving generalist species. Here, we characterised variation in species and trait composition and the relative importance of trait-matching and species abundance in shaping plant-Hymenoptera and plant-Diptera mutualisms in four meadows across an elevational gradient (2,725-3,910 m) in Yulong Snow Mountain, Southwest China. We also evaluated the effects of morphological traits of flower visitors and plant composition on their foraging specialisation (d' and normalised degree). There was a high degree of dissimilarity in the composition of Hymenoptera and Diptera visitors and their visited plants between communities. This variation was mainly driven by the spatial replacement of species. Both for plant-Hymenoptera and plant-Diptera networks, trait-matching between nectar tube depth and proboscis length was a stronger predictor of the interactions between temporally co-occurring plants and flower visitors than species abundance. Fourth-corner analyses revealed statistically significant trait-matching between nectar tube depth and proboscis length in plant-Hymenoptera networks at all sites, suggesting that Hymenoptera consistently foraged on plant species with nectar tube depths matching their proboscis lengths. By contrast, significant trait-matching in plant-Diptera networks was only observed at the two lower elevation sites. The species-level specialisation d' of flower visitors increased significantly as the proboscis length and the difference in nectar tube depth between the plant community and the plants visited by flower visitors increased. Our results highlight that the importance of trait-matching in shaping pairwise interactions and niche partitioning depends on the specific features (e.g. species composition and trait availability) of the plant-pollinator system. For specialised plant-Hymenoptera systems, trait-matching is an important determinant of species interactions, whereas for generalist plant-Diptera systems, trait-matching is relatively unimportant.

8.
Int Immunol ; 33(10): 529-540, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34491327

RESUMO

Coronavirus disease 2019 (COVID-19) has caused millions of deaths, and serious consequences to public health, economies and societies. Rapid responses in vaccine development have taken place since the isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the release of the viral genome sequence. By 21 May 2021, 101 vaccines were under clinical trials, and published data were available for 18 of them. Clinical study results from some vaccines indicated good immunogenicity and acceptable reactogenicity. Here, we focus on these 18 vaccines that had published clinical data to dissect the induced humoral and cellular immune responses as well as their safety profiles and protection efficacy.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Animais , Humanos , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia
9.
Chem Biol Interact ; 349: 109652, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520751

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for about 80-85% of total lung cancer cases. Identifying the molecular mechanisms of anti-tumor drugs is essential for improving therapeutic effects. Herein, we aim to investigate the role of thalidomide in the tumorigenicity of NSCLC. METHODS: The A549 xenograft nude mouse model was established to explore therapeutic effects of thalidomide. The expression of FGD5-AS1 was evaluated in carcinomatous and paracarcinomatous tissues from NSCLC patients as well as NSCLC cell lines. CCK-8 assay was performed to assess cell viability. The invasive capacity was examined using transwell assay. The tube formation assay was applied to determine cell angiogenesis. Flow cytometry was subjected to validate CD8+ T cell activity. The FGD5-AS1/miR-454-3p/ZEB1 regulatory network was analyzed using luciferase reporter, RIP and ChIP assays. RESULTS: Thalidomide reduced tumor growth and angiogenesis and increased CD8+ T cell ratio in a mouse model. Enhanced expression of FGD5-AS1 was positively correlated with the poor survival of NSCLC patients. Knockdown of FGD5-AS1 notably suppressed the proliferation, invasion and angiogenesis of cancer cells as well as the apoptosis of CD8+ T cells. Thalidomide targeted FGD5-AS1 to exert its anti-tumor activity in NSCLC. FGD5-AS1 acted as a sponge of miR-454-3p to upregulate ZEB1, thus increasing the expression of PD-L1 and VEGFA. Simultaneous overexpression of FGD5-AS1 and silencing of miR-454-3p reversed thalidomide-mediated anti-tumor effects in NSCLC. CONCLUSION: Thalidomide inhibits NSCLC angiogenesis and immune evasion via FGD5-AS1/miR-454-3p/ZEB1 axis-mediated regulation of VEGFA expression and PD-1/PD-L1 checkpoint.

10.
J Org Chem ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553932

RESUMO

N-Hydroxyphthalimide (NHPI)-mediated electrochemical denitrogenation of aroylhydrazides is developed for the first time. The in situ generated acyl radicals could be intramolecularly trapped to give fluorenones with high efficiencies. This electrochemical method features external oxidant- and transition metal-free conditions. In addition, the use of the catalytic amount of 2,4,6-collidine as the base makes this method more attractive for the syntheses of fluorenones.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34546628

RESUMO

The atomically precise control over the size, shape and structure of nanographenes (NGs) or the introduction of heteroatom dopants into their sp2 -carbon lattice confer them valuable electronic, optical and magnetic properties. Herein, we report on the design and synthesis of a hexabenzocoronene derivative embedded with graphitic nitrogen in its honeycomb lattice, achieved via on-surface assisted cyclodehydrogenation on the Au(111) surface. Combined scanning tunnelling microscopy/spectroscopy and non-contact atomic force microscopy investigations unveil the chemical and electronic structures of the obtained dicationic NG. Kelvin probe force microscopy measurements reveal a considerable variation of the local contact potential difference toward lower values with respect to the gold surface, indicative of its positive net charge. Altogether, we introduce the concept of cationic nitrogen doping of NGs on surfaces, opening new avenues for the design of novel carbon nanostructures.

12.
Biomed Res Int ; 2021: 5538643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557547

RESUMO

Background: Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. Methods: Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. Results: 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. Conclusion: The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

13.
Food Sci Biotechnol ; 30(8): 1129-1138, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34471566

RESUMO

This research aimed to detect Escherichia coli O157:H7 in milk based on immunomagnetic probe separation technology and quenching effect of gold nanoparticles to Rhodamine B. Streptavidin-modified magnetic beads (MBs) were combined with biotin-modified antibodies to capture E. coli O157:H7 specifically. Gold nanoparticle (AuNPs) was incubated with sulfhydryl-modified aptamers (SH-Aptamers) to obtain the Aptamers-AuNPs probe. After magnetic beads captured target bacteria and formed a sandwich structure with the gold nanoprobe, Rhodamine B was added into complex to obtain fluorescent signal changes. Our results demonstrated that the established method could detect E. coli O157:H7 in the range of 101-107 CFU/mL, and the limit of detection (LOD) was 0.35 CFU/mL in TBST buffer (pH = 7.4). In milk simulation samples, the LOD of this method was 1.03 CFU/mL. Our research provides a promising approach on the detection of E. coli O157:H7.

14.
Front Plant Sci ; 12: 710754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484271

RESUMO

Crop yield has been maintaining its attraction for researchers because of the demand of global population growth. Mutation of flowering activators, such as florigen, increases plant biomass at the expense of later flowering, which prevents crop maturity in the field. As a result, it is difficult to apply flowering activators in agriculture production. Here, we developed a strategy to utilize florigen to significantly improve soybean yield in the field. Through the screening of transgenic lines of RNAi-silenced florigen homologs in soybean (Glycine-max-Flowering Locus T Like, GmFTL), we identified a line, GmFTL-RNAi#1, with minor changes in both GmFTL expression and flowering time but with notable increase in soybean yield. As expected, GmFTL-RNAi#1 matured normally in the field and exhibited markedly high yield over multiple locations and years, indicating that it is possible to reach a trade-off between flowering time and high yield through the fine-tuning expression of flowering activators. Further studies uncovered an unknown mechanism by which GmFTL negatively regulates photosynthesis, a substantial source of crop yield, demonstrating a novel function of florigen. Thus, because of the highly conserved functions of florigen in plants and the classical RNAi approach, the findings provide a promising strategy to harness early flowering genes to improve crop yield.

15.
Small ; 17(40): e2102046, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34448349

RESUMO

Liver tumor is difficult to cure for its high degree of malignancy and rapid progression characteristics. Ferroptosis as a new model of inducing cell death is expected to break the treatment bottleneck of liver tumors. Here, a strategy to induce ferroptosis in HepG2 cells with acid-degradable tumor targeted nanosheets Cu-Hemin-PEG-Lactose acid (Cu-Hemin-PEG-LA) is proposed. After highly ingested by HepG2 cells, Cu-Hemin-PEG-LA nanosheets are degraded by weak acid and release Cu(II) and hemin, which consuming intracellular glutathione (GSH) content and increasing the expression of heme oxygenase 1 (HMOX1) protein, respectively. Furthermore, the expression of glutathione peroxidase 4 protein (GPX4) is down-regulated by consumption intracellular GSH content via converting GSH into glutathione oxidized (GSSG), which is named the classical mode. The intracellular Fe2+ content is overloaded by the significant up-regulation of HMOX1 expression, which is denoted as nonclassical mode. The synergistic effect of classical and nonclassical mode increased the intracellular lipid reactive oxide species, induced the occurrence of ferroptosis and up-regulated the expression of BH3 interacting domain death agonist (BID), apoptosis-inducing factor (AIF), and endonuclease G proteins (EndoG). The synergistic strategy demonstrate the excellent ferroptosis induction ability and antitumor efficacy in vivo, which provides great potential for the clinical transformation of ferroptosis.

16.
ACS Biomater Sci Eng ; 7(9): 4602-4613, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34365789

RESUMO

The mechanical properties of the natural extracellular matrix (ECM) change extensively, but these specific properties provide a relatively stable environment for resident cells. Although the effect of matrix stiffness on cell functions has been widely studied, the molecular mechanism was still not fully understood. Matrix stiffening is a common phenomenon in tissue damaging processes. To explore the effect of the increase in local matrix stiffness on cell behaviors, a three-dimensional (3D) cell culture system with a tunable modulus but constant other physical parameters was constructed by the alginate hydrogel with different molecular weights and cross-linking degrees. By using this culture system, the transcriptome response of mesenchymal stem cells (MSCs) to matrix stiffness was explored. Furthermore, a finite element model was developed to simulate the interaction between cells and the matrix. Results revealed that the increased matrix stiffness promoted the proliferation-related signaling of MSCs, and this process depended on the increased cortex tension caused by the activation of RAS and myosin II.


Assuntos
Células-Tronco Mesenquimais , Divisão Celular , Matriz Extracelular , Hidrogéis
17.
Angew Chem Int Ed Engl ; 60(39): 21575-21582, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34355481

RESUMO

The introduction of heteroatoms is one of the most important ways to modulate the intrinsic electronic structure of electrocatalysts to improve their catalytic activity. However, for transition metal chalcogenides with highly symmetric crystal structure (HS-TMC), the introduction of heteroatoms, especially those with large atomic radius, often induces large lattice distortion and vacancy defects, which may lead to structural phase transition of doped materials or structural phase reconstruction during the catalytic reaction. Such unpredictable situations will make it difficult to explore the connection between the intrinsic electronic structure of doped catalysts and catalytic activity. Herein, taking thermodynamically stable cubic CoSe2 phase as an example, we demonstrate that nitrogen incorporation can effectively regulate the intrinsic electronic structure of HS-TMC with structural phase stability and thus promote its electrocatalytic activity for the hydrogen evolution activity (HER). In contrast, the introduction of phosphorus can lead to structural phase transition from cubic CoSe2 to orthorhombic phase, and the structural phase of phosphorus-doped CoSe2 is unstable for HER.

18.
Nat Immunol ; 22(8): 958-968, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34267374

RESUMO

Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. Cross-reactive antibodies targeting the conserved fusion loop epitope (FLE) are known as the main sources of ADE. We design ZIKV immunogens engineered to change the FLE conformation but preserve neutralizing epitopes. Single vaccination conferred sterilizing immunity against ZIKV without ADE of DENV-serotype 1-4 infections and abrogated maternal-neonatal transmission in mice. Unlike the wild-type-based vaccine inducing predominately cross-reactive ADE-prone antibodies, B cell profiling revealed that the engineered vaccines switched immunodominance to dispersed patterns without DENV enhancement. The crystal structure of the engineered immunogen showed the dimeric conformation of the envelope protein with FLE disruption. We provide vaccine candidates that will prevent both ZIKV infection and infection-/vaccination-induced DENV ADE.


Assuntos
Anticorpos Facilitadores/imunologia , Antígenos Virais/imunologia , Reações Cruzadas/imunologia , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Zika virus/imunologia , Aedes , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Chlorocebus aethiops , Cricetinae , Vírus da Dengue/imunologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Vacinação , Células Vero , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle
19.
Emerg Microbes Infect ; 10(1): 1574-1588, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34289779

RESUMO

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.


Assuntos
Adenoviridae/genética , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , COVID-19 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/genética , Chlorocebus aethiops , Feminino , Vetores Genéticos/genética , Células HEK293 , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Pan troglodytes/virologia , Ligação Proteica , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Células Vero
20.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188590, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34271137

RESUMO

The formation of cyclinD-CDK4/6 complex plays vital roles in the cell cycle transition from G1 phase to S phase which is characterized by vigorous transcription and synthesis. Through cyclinD-CDK4/6-Rb axis, CDK4/6 inhibitors arrest the cell cycle in the G1 phase and block the proliferation of aggressive cells, exhibiting promising effects in containing the aggressiveness of breast cancers. To date, there are three CDK4/6 inhibitors approved by the U.S. Food and Drug Administration in treating advanced hormone receptor-positive breast cancer, including palbociclib, abemaciclib, and ribociclib. In fact, several preclinical experiments and clinical trials presented therapeutic effects of CDK4/6 inhibitor-based treatment in triple-negative breast cancer.

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