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1.
Biosens Bioelectron ; 171: 112676, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049564

RESUMO

Herein, a facile thermometer-like model of electrophoresis titration (ET) biosensor was proposed as an alternative tool for miRNA assay via moving reaction boundary (MRB) chip. For proof-of-concept demonstration, miRNA-122 and catalyzed hairpin assembly (CHA) were chosen as the model analyte and amplification, respectively. In the developed ET system, miRNA triggered the CHA with two hairpin probes (H1, H2) to yield H1-H2 duplexes with negative charges. Under an electric field, the duplexes moved into ET channel, and neutralized the acidic TAE buffer creating an MRB indicated by SYBR Green I (SGI). The model revealed that the MRB distance was as a function of logarithmic miRNA-122 content, indicating a facile sensing model. The relevant experiments were conducted and systemically validated the model of miRNA ET. Under the optimized conditions, the linear range of ET sensor was from 20 fM to 1 nM and the limit of detection (LOD) was 10 fM, showing a more than 100-fold sensitive increase in contrast to the one with a single CHA amplification. The mechanism of sensitive increase was well unveiled by the designed experiments. In addition, the ET biosensor had good selectivity, stability (less than 5% for intra-day and inter-day) and recovery (96%-110%), and was successfully applied for the assay of miRNA-122 and miRNA let-7a in real bio-fluids of serum and cancer cell lysate. Evidently, the proposed biosensor might be used as an alternative assay tool after nucleic acid amplification due to its high simplicity, sensitivity, specificity, linearity, stability and recovery.

2.
Sci Total Environ ; 754: 142144, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920403

RESUMO

Sustainable use of crop residues remains a challenge in main agricultural regions of China such as the Northeast Plain. Here we investigated the impacts of biomass burning on fine particle (PM2.5) during a six-month long heating season in the Harbin-Changchun (HC) metropolitan area, China's only national-level city cluster located in the severe cold climate region. Temporal variation of PM2.5 was found to coincide with that of levoglucosan. This was attributed to the strong contribution of biomass burning to organic aerosol (the dominant component in PM2.5), as supported by the source apportionment results and high levoglucosan-to-organic carbon (OC) ratios. Furthermore, the variation of biomass burning contribution was inferred to be driven mainly by agricultural fires with relatively low combustion efficiencies, based on a synthesis of the relationship between OC and elemental carbon (EC), the dependence of EC on carbon monoxide, and the relative abundances of different tracers for biomass burning. Nitrate formation was enhanced during biomass burning episodes whereas no evidence was observed to indicate enhanced sulfate formation or net increase of OC mass due to secondary formation. This study demonstrates the importance of open burning as a source of haze pollution in the HC region.

3.
Sci Total Environ ; 754: 142085, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898782

RESUMO

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are considered to be related to diabetes, but studies of the association between phenolic EDCs and gestational diabetes mellitus (GDM) are limited. OBJECTIVES: To assess associations of maternal urinary bisphenol A (BPA), nonylphenol (NP), and 2-tert-octylphenol (2-t-OP) with GDM occurrence. METHODS: A cross-sectional study was performed among 390 Chinese women at 24-28 weeks of gestation. GDM was diagnosed with a 2-h 75-g oral glucose tolerance test (OGTT). BPA, NP, and 2-t-OP concentrations were determined in urine samples. Linear and logistic regression tests evaluated associations of BPA, NP, and 2-t-OP with blood glucose levels and GDM prevalence. RESULTS: The 2-t-OP concentrations in GDM patients were significantly higher than in non-GDM women with median values of 2.23 µg/g Cr and 1.79 µg/g Cr, respectively. No significant difference was observed in BPA and NP. Urinary 2-t-OP was positively associated with blood glucose levels after adjustment for several confounding factors and urinary BPA and NP. Higher 2-t-OP levels were associated with higher odds of GDM (OR: 5.78; 95% CI: 2.04, 16.37), whereas higher NP levels were associated with lower odds (OR: 0.22; 95% CI: 0.05, 0.85) in the adjusted models. In addition, compared to the first quartile of 2-t-OP, the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GDM in the second, third, and fourth quartiles were 2.81 (1.23, 6.42), 3.01 (1.30, 6.93), and 5.49 (2.24, 13.46), respectively. CONCLUSION: Our study indicates that, for the first time to our knowledge, exposure to 2-t-OP is associated with a higher risk of GDM. However, higher NP exposure is associated with lower GDM risk. Further studies are necessary to affirm the associations of 2-t-OP and NP with GDM, and to elucidate the causality of these findings.


Assuntos
Diabetes Gestacional , Disruptores Endócrinos , Glicemia , Estudos Transversais , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Estrogênios , Feminino , Humanos , Gravidez
4.
J Hazard Mater ; 402: 123435, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717541

RESUMO

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in soil aroused increasing concern, however there is little information about their transport in porous media, which is urgently needed to better control their environmental risks. In this study, saturated sand columns (considering the coupled effect of solution cation type and pH) and a two-site nonequilibrium transport model (TSM) were used to investigate the transport behaviors and mechanisms of PFOA and PFOS. Breakthrough data and the TSM parameters showed PFOA had higher mobility than PFOS, and divalent cation could inhibit their transport by increasing the nonequilibrium interactions between them and the sand. pH had little influence on PFOA migration when there was only monovalent cation in the solution since PFOA had limited affinity with the sand, however, polyvalent cation could provide additional adsorption sites for it through cation bridging and enhance the effect of pH. Differently, decreasing pH inhibited the transport of PFOS more significantly, and the effect was stronger than that of changing cation type. That proved mechanisms like hydrogen-bonding which were sensitive to solution pH played an important role in PFOS migration. These results provide important scientific basis to the remediation strategy and the migration prediction model development of PFOA and PFOS.

5.
RNA Biol ; : 1-12, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151124

RESUMO

Treatment of central nervous system (CNS) demyelination is greatly hindered by lack of the knowledge regarding to underlying molecular mechanisms as well as therapeutic agents. Here, we report a novel small molecule agent, gastrodin (GAS), which can significantly promote CNS myelination in in vivo mice models. By using high-throughput sequencing analysis, we discover a key long non-coding RNA Gm7237 that can enhance CNS myelination and is up-regulated by GAS. Through using bioinformatic analysis and experimental validations, we further unravel that microRNA-142a (miR-142a) and its target myelin gene regulatory factor (MRF) is under the direct regulation by Gm7237. Finally, we demonstrate that Gm7237/miR-142a/MRF axis is the key pathway involved in CNS myelination mediated by GAS. Overall, our results provide not only a novel agent for therapeutic treatment of CNS demyelination but also a molecular basis responsible for GAS-promoted CNS myelination.

6.
Ear Nose Throat J ; : 145561320971929, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155846

RESUMO

Extramedullary plasmacytoma (EMP) is a malignant tumor formed by monoclonal abnormal proliferation of plasma cells, which is mainly characterized by localized masses and very rare in the larynx, particularly in the false vocal cord. We present a larynx EMP that arises from the false cord without systematic involvement. After surgical resection, the patient received adjuvant radiotherapy and was recurrence-free during the 8-month follow-up.

8.
Am J Ophthalmol ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130046

RESUMO

PURPOSE: To compare the sensitivity, specificity, accuracy, and inter-observer agreement of the two most commonly used classification systems for conjunctival melanocytic intraepithelial lesions with the new WHO classification. DESIGN: Retrospective case series and evaluation of classification systems. METHODS: Pathology and medical records of all patients, who underwent primary biopsy for conjunctival primary acquired melanosis (PAM) at Wills Eye Hospital between 1974 and 2002, with at least 36 months follow-up were reviewed. Data collected included age, sex, clinical findings, recurrence, and progression to melanoma. Twelve ophthalmic pathologists analyzed scanned hematoxylin-and-eosin stained virtual microscopic slides using three classification systems: PAM, conjunctival melanocytic intraepithelial neoplasia (C-MIN) and the World Health Organization (WHO) 4th edition classification of conjunctival melanocytic intraepithelial lesions (CMIL). Observer agreement, sensitivity, specificity, and diagnostic accuracy of each classification system were assessed. RESULTS: There were 64 patients who underwent 83 primary excisions with cryotherapy for conjunctival PAM, with adequate tissue for histopathologic evaluation. The inter-observer percent agreement in distinction between the low-grade and high-grade lesions was 76% for PAM, 67% for C-MIN, and 81% for WHO classification system. Low-grade lesions provided the greatest interpretative challenge with all three classification systems. The three classification systems had comparable accuracy of 81%-83% in their ability to identify lesions with potential for recurrence. CONCLUSIONS: This study highlights the comparable strengths and limitations of the three classification systems for conjunctival melanocytic intraepithelial lesions and suggests that the simplified WHO classification scheme is appropriate for evaluation of these lesions.

9.
Rev Sci Instrum ; 91(10): 105109, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33138597

RESUMO

We present an approach to determine the absolute thickness profile of flat liquid jets, which takes advantage of the information of thin film interference combined with light absorption, both captured in a single microscopic image. The feasibility of the proposed method is demonstrated on our compact experimental setup used to generate micrometer thin, free-flowing liquid jet sheets upon collision of two identical laminar cylindrical jets. Stable operation was achieved over several hours of the flat jet in vacuum (10-4 mbar), making the system ideally suitable for soft x-ray photon spectroscopy of liquid solutions. We characterize the flat jet size and thickness generated with two solvents, water and ethanol, employing different flow rates and nozzles of variable sizes. Our results show that a gradient of thickness ranging from a minimal thickness of 2 µm to over 10 µm can be found within the jet surface area. This enables the tunability of the sample thickness in situ, allowing the optimization of the transmitted photon flux for the chosen photon energy and sample. We demonstrate the feasibility of x-ray absorption spectroscopy experiments in transmission mode by measuring at the oxygen K-edge of ethanol. Our characterization method and the description of the experimental setup and its reported performance are expected to expand the range of applications and facilitate the use of flat liquid jets for spectroscopy experiments.

10.
Environ Sci Technol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174716

RESUMO

Since 2013, clean-air actions in China have reduced ambient concentrations of PM2.5. However, recent studies suggest that ground surface O3 concentrations increased over the same period. To understand the shift in air pollutants and to comprehensively evaluate their impacts on health, a spatiotemporal model for O3 is required for exposure assessment. This study presents a data-fusion algorithm for O3 estimation that combines in situ observations, satellite remote sensing measurements, and model results from the community multiscale air quality model. Performance of the algorithm for O3 estimation was evaluated by five-fold cross-validation. The estimates are highly correlated with the in situ observations of the maximum daily 8 h averaged O3 (R2 = 0.70). The mean modeling error (measured using the root-mean-squared error) is 26 µg/m3, which accounts for 29% of the mean level. We also found that satellite O3 played a key role to improve model performance, particularly during warm months. The estimates were further used to illustrate spatiotemporal variation in O3 during 2013-2017 for the whole country. In contrast to the reduced trend of PM2.5, we found that the population-weighted O3 mean increased from 86 µg/m3 in 2013 to 95 µg/m3 in 2017, with a rate of 2.07 (95% CI: 1.65, 2.48) µg/m3 per year at the national level. This increased trend in O3 suggests that it is becoming an important contributor to the burden of diseases attributable to air pollutants in China. The developed method and the results generated from this study can be used to support future health-related studies in China.

11.
Aging (Albany NY) ; 12(21): 21747-21757, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33177243

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive brain disorder characterized by cognitive skills deterioration that affects many elderly individuals. The identified genetic loci for AD failed to explain the large variability in AD and very few causal factors have been identified so far. RESULTS: mvMR showed that increasing years of schooling (OR=0.674, 95%CI: 0.571-0.796, P=3.337E-06) and genetically elevated HDL cholesterol (OR ranging from 0.697 to 0.830, P=6.940E-10) were inversely associated with AD risk, genetically predicted total cholesterol (OR=1.300, 1.196 to 1.412; P=6.223E-10) and LDL cholesterol (OR=1.193, 1.097 to 1.296, P=3.564E-05) were associated with increasing AD risk. Genetically predicted FG was suggestively associated with increased AD risk. Furthermore, MR-BMA analysis also confirmed FG and years of schooling as two of the top five causal risk factors for AD. CONCLUSIONS: Our findings might provide us novel insights for treatment and intervention into the causal risk factors for AD or AD-related complex diseases. METHODS: By using extension methods of Mendelian randomization (MR)--multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA), we intend to estimate the potential causal relationship between nine risk factors and AD outcome and try to prioritize the most causal risk factors for AD.

12.
J Exp Bot ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200773

RESUMO

Senescence is induced by endogenous physiological changes or exogenous stresses in plants. Here, we isolated two alleles of a novel rice (Oryza sativa L.) mutant, yellow and premature dwarf 1 (ypd1). The ypd1 mutants exhibited a yellow and dwarf phenotype from germination, and premature senescence starting at tillering. Moreover, the ypd1 mutants were sensitive to high light, which accelerated cell death and senescence. Consistent with their yellow phenotype, the ypd1 mutants had abnormal chloroplasts and lower levels of photosynthetic pigments. Trypan blue staining, TUNEL experiments, NBT staining, and DAB staining demonstrated that the ypd1 mutants showed cell death and accumulated reactive oxygen species. Moreover, the ypd1 mutants showed increased expression of senescence-associated genes. Map-based cloning revealed a substitution (G→A) in exon 6 (ypd1-1) and 13 (ypd1-2) of LOC_Os06g13050 that affected splicing and caused premature termination of the encoded protein. YPD1 was preferentially expressed in the leaf and encodes an LRR-Like1 (LRRL1) protein. Complementation, overexpression, and targeted deletion experiments confirmed that the mutations in YPD1 cause the ypd1 phenotype. YPD1 localized on the chloroplast membrane. These findings revealed that the novel rice LRRL1 protein YPD1 affects rice chloroplast development and leaf senescence.

13.
Orthop Surg ; 12(5): 1520-1525, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33200574

RESUMO

BACKGROUND: Snapping triceps tendon is an increasingly recognized clinical entity, which is associated with a variety of pathologic factors. The causative factors include inherited structural or developmental variations, post-traumatic malalignment, and other reasons. The main complaint of patients with snapping lateral triceps are the snapping sensation, mild muscle weakness of elbow extension, with or without tenderness in distal triceps tendon. Many treatment options have been reported previously, including tendon resection and redirection. CASE PRESENTATION: We present the case of a 19-year-old boy with post-traumatic distal lateral head of triceps tendon dislocation who complained of extension weakness and snapping sensation in his left elbow. Then, we used two-strand-overhand locking (TSOL) knot combined with double pulley technique to redirect the snapping triceps tendon. CONCLUSION: The patient recovered well after the operation without complaining of discomfort. This fixing and redirection tendon technique, described previously for repairing rotator cuff tears, may be applied in a similar fashion for the snapping triceps tendon with promising clinical results.

14.
Life Sci ; : 118786, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221346

RESUMO

AIMS: To assess the effects of three specific exercise training modes, aerobic exercise (A), resistance training (R) and autonomous climbing (AC), aimed at proposing a cross-training method, on improving the physical, molecular and metabolic characteristics of mice without many side effects. MATERIALS AND METHODS: Seven-week-old male mice were randomly divided into four groups: control (C), aerobic exercise (A), resistance training (R), and autonomous climbing (AC) groups. Physical changes in mice were tracked and analysed to explore the similarities and differences of these three exercise modes. Histochemistry, quantitative real-time PCR (RT-PCR), western blot (WB) and metabolomics analysis were performed to identify the underlying relationships among the three training modes. KEY FINDINGS: Mice in the AC group showed better body weight control, glucose and energy homeostasis. Molecular markers of myogenesis, hypertrophy, antidegradation and mitochondrial function were highly expressed in the muscle of mice after autonomous climbing. The serum metabolomics landscape and enriched pathway comparison indicated that the aerobic oxidation pathway (pentose phosphate pathway, galactose metabolism and fatty acid degradation) and amino acid metabolism pathway (tyrosine, arginine and proline metabolism) were significantly enriched in group AC, suggesting an increased muscle mitochondrial function and protein balance ability of mice after autonomous climbing. SIGNIFICANCE: We propose a new exercise mode, autonomous climbing, as a convenient but effective training method that combines the beneficial effects of aerobic exercise and resistance training.

15.
Stem Cells Dev ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231507

RESUMO

Thus far, there are more than known 150 modifications to RNA,in which common internal modifications of mRNA include N6-Methyladenosine(m6A), N1-methyladenosine(m1A) and 5-methylcytosine (5-mC). Among them, m6A RNA modification is one of the highest abundance modifications in eukaryotes, regulating mechanisms controlling gene expression at the molecular level. As an invertible and dynamic epigenetic marker, m6A base modification influences almost all vital biological processes, cellular components, and molecular functions. Once the m6A modification process is abnormal, a series of diseases -including cancer, neurological diseases, and growth disorders -will be caused. Besides, several base modification activities also have been existed by non-coding RNAs, for instance, microRNAs (miRNAs), and circular RNAs (circRNAs) ,long non-coding RNAs (lncRNAs), which dynamically regulated during Bone and cartilage Pathophysiology processes. Therefore,it has now been clear that dynamic modification on coding RNAs and non-coding RNAs represents a completely new way to modulate genetic information. In this review, we highlight up-to-date progress and applications of N6-methyladenosine (m6A) RNA modification in bone and cartilage pathophysiology, and discuss the pathological roles and underlying molecular mechanism of m6A modifications in osteoarthritis and osteoporosis pathogenesis.

16.
Plant Physiol Biochem ; 157: 359-369, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33189056

RESUMO

Leaves are the primary structures responsible for photosynthesis, making leaf morphology one of the most important traits of rice plant architecture. Both plant architecture and nutrient utilization jointly affect rice yield, however, their molecular association is still poorly understood. We identified a rice mutant, leaf width 5 (lw5), that displayed small grains and wide leaves and possesses characteristics typical of a small "sink" and a large "source". Map-based cloning and CRISPR-Cas9 gene editing indicated that LW5 affects both the plant architecture and yield. It is an allele of D1, encoding the rice G protein α subunit. The loss of LW5 functioning leads to an increase in the rate of photosynthesis, vascular bundles, and chlorophyll content. However, the grain-straw ratio and the rate of grain filling decreased significantly. The detection results of 15N-ammonium nitrate and an expression analysis of genes associated with nitrogen demonstrated that LW5 serves an important role in nitrate uptake and transport. LW5 affects plant architecture and grain size by regulating nitrogen transfer. These results provide a theoretical foundation for further research surrounding the molecular mechanism of "source-sink" balance in rice and suggest novel methods of molecular design for the cultivation of breeding super rice in ideal plant types.

17.
Neurotherapeutics ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33205381

RESUMO

Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers.

18.
Transpl Int ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33205460

RESUMO

Proteinuria and transplant glomerulopathy (TG) are common in kidney transplantation. To date, there is limited knowledge regarding proteinuria in different types of TG and its relationship to allograft survival. A retrospective cohort analysis of TG patients from indication biopsies was performed to investigate the relationship of proteinuria, histology, and graft survival. One hundred and seven (57.5%) out of 186 TG patients lost their grafts with a median survival of 14 (95% confidence interval [CI] 10-22) months after diagnosis. Proteinuria ≥ 1 g/24h at the time of biopsy was detected in 87 patients (46.8%) and the median of proteinuria was 0.89 (range 0.05-6.90) g/24h. TG patients with proteinuria ≥1 g/24h had worse 5-year graft survival (29.9% vs 53.5%, P=0.001) compared with proteinuria <1 g/24h. Proteinuria was associated with graft loss in univariable Cox regression (hazard ratio [HR] 1.25, 95% CI, 1.11-1.41, P<0.001), and in multivariable analysis (adjusted HR 1.26, 95% CI 1.11-1.42, P<0.001) independent of other risk factors including creatinine at biopsy, positive C4d, history of rejection, and Banff lesion score mesangial matrix expansion. In this cohort of TG patients, proteinuria at indication biopsy is common and associated with a higher proportion of graft loss.

19.
J Integr Plant Biol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205861

RESUMO

In plants, recognition of small secreted peptides, such as damage/danger-associated molecular patterns (DAMPs), regulates diverse processes, including stress and immune responses. Here, we identified an SGPS (Ser-Gly-Pro-Ser) motif-containing peptide, Nicotiana tabacum NtPROPPI, and its two homologs in Nicotiana benthamiana, NbPROPPI1 and NbPROPPI2. Phytophthora parasitica infection and salicylic acid (SA) treatment induced NbPROPPI1/2 expression. Moreover, SignalP predicted that the 89-amino acid NtPROPPI includes a 24-amino acid N-terminal signal peptide and NbPROPPI1/2-GFP fusion proteins were mainly localized to the periplasm. Transient expression of NbPROPPI1/2 inhibited P. parasitica colonization, and NbPROPPI1/2 knockdown rendered plants more susceptible to P. parasitica. An eight-amino-acid segment in the NbPROPPI1 C-terminus was essential for its immune function and a synthetic 20-residue peptide, NbPPI1, derived from the C-terminus of NbPROPPI1 provoked significant immune responses in N. benthamiana. These responses led to enhanced accumulation of reactive oxygen species, activation of mitogen-activated protein kinases, and up-regulation of the defense genes Flg22-induced receptor-like kinase (FRK) and WRKY DNA-binding protein 33 (WRKY33). The NbPPI1-induced defense responses require Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1). These results suggest that NbPPI1 functions as a DAMP in N. benthamiana; this novel DAMP provides a potentially useful target for improving resistance to P. parasitica. This article is protected by copyright. All rights reserved.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33205941

RESUMO

Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8+ cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs). We first confirmed that different antigen-loaded HBc VLP monomers could be assembled into nanoparticles (hybrid VLPs). Hybrid VLPs could slightly enhance bone marrow-derived dendritic cell maturation in vitro. Strikingly, hybrid VLPs could generate antigen-specific antitumor immunity and innate immunity in vivo which could significantly inhibit tumor growth or metastatic formation in a subcutaneous tumor or lung metastatic tumor model, respectively. Moreover, dual-epitope vaccination generated enhanced T-cell responses that potently inhibited tumor growth and metastatic formation. Together, this study provides a new powerful concept for cancer immunotherapy and suggests a novel design for VLP-based personalized nanomedicine.

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