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1.
Heliyon ; 10(7): e27681, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590877

RESUMO

Background: Chronic Rhinosinusitis is a common disease in children. The main function of CFTR is to maintain the thickness of the mucous layer on the surface of the nasal mucosa. CFTR disease-causing variant can cause CFTR protein dysfunction and induce or aggravate chronic infection. However, the carrying status of the CFTR variants in the Chinese population is not clear. Objective: To study the frequency and variants of CFTR in Chinese children with CRS and to analyze the CFTR variants and the clinical characteristics and susceptibility to CRS. Methods: Whole Exome Sequencing was performed to analyze the CFTR genes in a total of 106 CRS children from the Chinese mainland area. The CFTR variants, frequency and clinical data were summarized and analyzed. Results: A total of 31 CFTR variants were detected, of which the carrying rate of 7 sites was significantly higher than that of the population database. 88 patients carried more than 2 variants. 37 people carried variants (MAF < 0.05), of which 91.89% had a history of recurrent upper respiratory infections, 16 had nasal polyps, 5 had bronchiectasis, and 1 was diagnosed with CF-related disorders. Conclusion: The carrying rate of CFTR variants in Chinese CRS children increased, and the highest rates of variants (MAF < 0.05) are p.I556V, p. E217G, c.1210-12[T]. Carrying multiple CFTR variants, especially p.E217G, p.I807 M, p.V920L and c.1210-12[T] may lead to increased susceptibility to CRS. There are CF-related disorders in patients with CRS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38676511

RESUMO

OBJECTIVE: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow down disease progression. This study aimed to investigate the potential of the NeuroProtect (NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD. We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models. METHODS: To predict functional pathways and potential downstream targets of NP intervention, we employed network pharmacology. The preventative impact of the NP formula was assessed using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression. RESULTS: Network pharmacology analysis revealed 145 drug-disease interactions and identified 5 core active targets associated with AD. Molecular docking results demonstrated strong binding affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1 and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP formula significantly ameliorated pathological changes, decreased the Aß42/Aß40 ratio in the hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula's ability to reverse the inhibitory effects of Aß25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a, Stat3, and Vegfa. CONCLUSION: Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as a key target.

3.
Sci Adv ; 10(14): eadl4600, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579006

RESUMO

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.


Assuntos
Genoma , Genômica , Animais , Humanos , Macaca mulatta , Encéfalo
4.
Wiley Interdiscip Rev RNA ; 15(2): e1845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605485

RESUMO

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new. In this short review, we will summarize the definition and features of human de novo genes and clarify their process of origination from ancestral non-coding genomic regions. In addition, we define the favored precursors, or "hopeful monsters," for the origin of de novo genes and present a discussion of the functional significance of these young genes in brain development and tumorigenesis in humans. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.


Assuntos
Evolução Molecular , RNA , Humanos
5.
Neuroreport ; 35(3): 160-169, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38305109

RESUMO

To investigate the distribution and characteristics of lymphatic vessels within the central nervous system, we focus on the meninges of the spinal cord and brain parenchyma in mice. Additionally, we aim to provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels, while optimizing the perfusion parameters to improve histomorphological quality. Male C57BL/6J mice were randomly divided into four groups, with each group assigned a specific perfusion parameter based on perfusion volumes and temperatures. Immunofluorescence staining of lymphatics and blood vessels was performed on both meningeal and the brain tissue samples. Statistical analysis was performed using one-way analysis of variance to compare the groups, and a significant level of P < 0.05 was considered statistically significant. Our study reports the presence of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice. We highlight the crucial role of high perfusion volume of paraformaldehyde with low temperature in fixation for achieving optimal results. We provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice, which contribute to our understanding of the distribution and characteristics of lymphatic vessels within the central nervous system. Further research is warranted to explore the functional implications of these lymphatic vessels and their potential therapeutic significance in neurodegenerative and neuroinflammatory diseases.


Assuntos
Sistema Nervoso Central , Vasos Linfáticos , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/fisiologia , Meninges/diagnóstico por imagem , Encéfalo , Perfusão
6.
Acad Radiol ; 31(3): 1014-1023, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37714721

RESUMO

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.


Assuntos
Fibrossarcoma , Imageamento por Ressonância Magnética , Animais , Camundongos , Camundongos Nus , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Biomarcadores , Movimento (Física) , Fibrossarcoma/diagnóstico por imagem
7.
Acta Biochim Biophys Sin (Shanghai) ; 56(1): 71-81, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38013469

RESUMO

Epithelial-mesenchymal transformation (EMT) plays an important role in the progression of diabetic nephropathy. Dexmedetomidine (DEX) has shown renoprotective effects against ischemic reperfusion injury; however, whether and how DEX prevents high glucose-induced EMT in renal tubular epithelial cells is incompletely known. Here, we conduct in vitro experiments using HK-2 cells, a human tubular epithelial cell line. Our results demonstrate that high glucose increases the expressions of EMT-related proteins, including Vimentin, Slug, Snail and Twist, while decreasing the expression of E-cadherin and increasing Cdk5 expression in HK-2 cells. Both Cdk5 knockdown and inhibition by roscovitine increase the expressions of E-cadherin while decreasing the expressions of other EMT-related markers. DEX inhibits Cdk5 expression without affecting cell viability and changes the expressions of EMT-related markers, similar to effects of Cdk5 inhibition. Furthermore, Cdk5 is found to interact with Drp1 at the protein level and mediate the phosphorylation of Drp1. In addition, Drp1 inhibition with mdivi-1 could also restrain the high glucose-induced EMT process in HK-2 cells. Immunofluorescence results show that roscovitine, Mdivi-1 and DEX inhibit high glucose-induced intracellular ROS accumulation, while the oxidant H 2O 2 eliminates the protective effect of DEX on the EMT process. These results indicate that DEX mitigates high glucose-induced EMT progression in HK-2 cells via inhibition of the Cdk5/Drp1/ROS pathway.


Assuntos
Dexmedetomidina , Transição Epitelial-Mesenquimal , Transdução de Sinais , Humanos , Caderinas/metabolismo , Dexmedetomidina/farmacologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/toxicidade , Glucose/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Roscovitina/metabolismo , Roscovitina/farmacologia , Quinase 5 Dependente de Ciclina/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/metabolismo , Dinaminas/efeitos dos fármacos , Dinaminas/metabolismo
8.
Br J Anaesth ; 132(3): 528-540, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38105166

RESUMO

BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.


Assuntos
Dexmedetomidina , Ketamina , Propofol , Humanos , Propofol/farmacologia , Ketamina/farmacologia , Dexmedetomidina/farmacologia , Eletroencefalografia , Encéfalo
9.
J Magn Reson Imaging ; 59(1): 7-31, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37154415

RESUMO

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Imageamento por Ressonância Magnética
10.
Sci Adv ; 9(42): eadh7912, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37862411

RESUMO

While N6-methyldeoxyadenine (6mA) modification is a fundamental regulation in prokaryotes, its prevalence and functions in eukaryotes are controversial. Here, we report 6mA-Sniper to quantify 6mA sites in eukaryotes at single-nucleotide resolution, and delineate a 6mA profile in Caenorhabditis elegans with 2034 sites. Twenty-six of 39 events with Mnl I restriction endonuclease sites were verified, demonstrating the feasibility of this method. The levels of 6mA sites pinpointed by 6mA-Sniper are generally increased after Pseudomonas aeruginosa infection, but decreased in strains with the removal of METL-9, the dominant 6mA methyltransferase. The enrichment of these sites on specific motif of [GC]GAG, the selective constrains on them, and their coordinated changes with METL-9 levels thus support an active shaping of the 6mA profile by methyltransferase. Moreover, for regions marked by 6mA sites that emerged after infection, an enrichment of up-regulated genes was detected, possibly mediated through a mutual exclusive cross-talk between 6mA and H3K27me3 modification. We thus highlight 6mA regulation as a previously neglected regulator in eukaryotes.


Assuntos
Eucariotos , Nucleotídeos , Eucariotos/genética , Metilação de DNA , Adenina , Metiltransferases/genética
11.
Inorg Chem ; 62(16): 6527-6536, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37057413

RESUMO

Metal-organic frameworks (MOFs), a novel type of porous crystalline material, have aroused widespread interest in lithium-ion batteries (LIBs). The design and preparation of MOF electrodes with a stable structure and excellent electrochemical performance are primary concerns for improving the capacity of LIBs. Among them, two-dimensional (2D) materials with larger specific surface areas, richer active sites, and higher aspect ratios have great potential. We adopted a facile approach to synthesize unique Co-MOF nanosheets with a 2D flaky morphology and a mesoporous structure. In addition, low-temperature calcination increases the specific surface area and improves the porosity to achieve mass transfer. Sample M2 delivers high specific capacities and long lives (1402.0 mA h g-1 after 100 cycles at 500 mA g-1 and 462.4 mA h g-1 after 300 cycles at 1.0 A g-1) when the calcination temperature is 200 °C. Significant improvements in the cycle life and stability are attributed to the 2D flaky structure of the M2 sample and the available low-temperature calcination activation, which provide a simple strategy for the fabrication of inexpensive and excellent anodes for LIBs.

12.
J Environ Manage ; 307: 114538, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066196

RESUMO

Commercial digesters handling complex waste and organic overloading often encounter unbalanced conditions or failures. With limited studies on the digester recovery from an industry-based waste stream, a complex and high-strength digestate containing up to 79 g COD l-1 from acidified commercial digester was investigated for biochar and alkaline treatments. The addition of biochar and calcium hydroxide successfully decomposed excessive volatile fatty acid up to 18.9 ± 2.5 g l-1 and resumed methane production. The maximum methane yield was obtained from the digester amended with biochar (373.4 ± 6.0 ml g COD-1), followed by calcium hydroxide (350.1 ± 2.5 ml g COD-1). Calcium hydroxide treatment showed a shorter lag phase than the biochar by 44%. Methane production could not be recovered by using sodium hydroxide or untreated digester. This study provides a strategic approach to justify the use of alkalis for restoring sour digesters from industry-based waste streams.


Assuntos
Álcalis , Reatores Biológicos , Anaerobiose , Carvão Vegetal , Metano
13.
Front Pediatr ; 10: 711241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36776682

RESUMO

Background: While the association between father absence and youth hostility has been well-documented among depressed youths, there is a lack of research on the potential mechanism underlying such an association. This study aimed to test a serial mediation model of self-esteem and frustration tolerance on the link between father absence and youth hostility. Methods: A total of 137 Chinese youths with major depressive disorder were recruited from Wuhan Mental Health Center. They completed a survey including the Father Absence Questionnaire to measure father absence, the Chinese Hostility Inventory (CHI) to measure hostility, the Psychological Endurance Questionnaire to measure frustration tolerance, and the Self-esteem Scale (SES) to measure self-esteem. A series of multiple linear regression models were employed to assess the associations among father absence, self-esteem, frustration tolerance, and hostility. Results: Although father absence was modestly associated with hostility (r = 0.30, p < 0.001), subsequent serial mediation analysis showed that father absence was not directly related to hostility (ß = 0.06, p = 0.29) when self-esteem and frustration tolerance were included in the model. High levels of father absence had an adverse effect on levels of self-esteem, which decreased levels of frustration tolerance, and thus higher levels of hostility among depressed youths. The indirect effects of father absence on hostility through self-esteem, frustration tolerance, as well as through self-esteem and frustration tolerance serially accounted for 28%, 24%, and 24% of the total effect, respectively. Conclusion: Our study tested a serial mediation model of self-esteem and frustration tolerance as mediators between father absence and hostility among depressed youths. The findings strengthened our understanding of the potential mechanism underlying the association between self-esteem and frustration tolerance, which may provide useful guidance for future intervention programs.

14.
Medicine (Baltimore) ; 100(51): e28207, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34941079

RESUMO

RATIONALE: Central neurocytoma occurring outside the ventricles is known as extraventricular neurocytoma (EVN). EVN is rare and its magnetic resonance imaging (MRI) findings vary greatly and overlap with the imaging features of other intracerebral primary tumors. PATIENT CONCERNS: A 21-year-old woman with an intrauterine pregnancy of 18+2 weeks complained of dizziness and headache for 3 months. DIAGNOSIS: A 8.6 cm × 5.8 cm × 3.7 cm space-occupying lesion was seen in the right frontal lobe on MRI, with mixed long signals on T1-weighted imaging and mixed slightly long signals on T2-weighted imaging, slightly hyperintense on T2-weighted imaging fluid attenuated inversion recovery images, and a large-scope long T1-weighted imaging and long T2-weighted imaging cystic component at the center of the lesion. A thick fence-like enhancement of the solid component at the periphery of the lesion was observed after injecting a contrast medium, while the internal cystic component was not enhanced. The MRI diagnosis was of glioma. The lesion was pathologically confirmed as an atypical central neurocytoma of the right frontal lobe. INTERVENTIONS: Resection of the lesion and postoperative radiotherapy. OUTCOMES: The patient was lost to follow-up. LESSONS: EVN can be considered as a differential diagnosis for lesions occurring in the cerebral hemispheres of young patients with cystic degeneration, thick fence-like enhancement, and peritumoral edema on MRI.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neurocitoma/diagnóstico , Adulto , Neoplasias Encefálicas/radioterapia , Meios de Contraste , Tontura/etiologia , Feminino , Lobo Frontal/diagnóstico por imagem , Cefaleia/etiologia , Humanos , Neurocitoma/radioterapia , Neurocitoma/terapia , Lesões Pré-Cancerosas , Gravidez
15.
Front Cell Dev Biol ; 9: 660005, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277607

RESUMO

The development of temozolomide (TMZ) resistance in glioma leads to poor patient prognosis. Sorafenib, a novel diaryl urea compound and multikinase inhibitor, has the ability to effectively cross the blood-brain barrier. However, the effect of sorafenib on glioma cells and the molecular mechanism underlying the ability of sorafenib to enhance the antitumor effects of TMZ remain elusive. Here, we found that sorafenib could enhance the cytotoxic effects of TMZ in glioma cells in vitro and in vivo. Mechanistically, the combination of sorafenib and TMZ induced mitochondrial depolarization and apoptosis inducing factor (AIF) translocation from mitochondria to nuclei, and this process was dependent on STAT3 inhibition. Moreover, the combination of sorafenib and TMZ inhibited JAK2/STAT3 phosphorylation and STAT3 translocation to mitochondria. Inhibition of STAT3 activation promoted the autophagy-associated apoptosis induced by the combination of sorafenib and TMZ. Furthermore, the combined sorafenib and TMZ treatment induced oxidative stress while reactive oxygen species (ROS) clearance reversed the treatment-induced inhibition of JAK2/STAT3. The results indicate that sorafenib enhanced the temozolomide sensitivity of human glioma cells by inducing oxidative stress-mediated autophagy and JAK2/STAT3-AIF axis.

16.
J Nanobiotechnology ; 18(1): 160, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160377

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. No disease-modifying strategy to prevent or delay AD progression currently exists. Aß oligomers (AßOs), rather than monomers or fibrils, are considered as the primary neurotoxic species. Therapeutic approaches that direct against AßOs and promote Aß clearance may have great value for AD treatment. RESULTS: We here reported a multifunctional superparamagnetic iron oxide nanoparticle conjugated with Aß oligomer-specific scFv antibody W20 and class A scavenger receptor activator XD4 (W20/XD4-SPIONs). Besides the diagnostic value, W20/XD4-SPIONs retained the anti-Aß properties of W20 and XD4 by inhibiting Aß aggregation, attenuating AßO-induced cytotoxicity and increasing microglial phagocytosis of Aß. When applied to APP/PS1 mice, W20/XD4-SPIONs significantly rescued cognitive deficits and alleviated neuropathology of AD mice. CONCLUSION: These results suggest that W20/XD4-SPIONs show therapeutic benefits for AD. In combination with the early diagnostic property, W20/XD4-SPIONs present as a promising agent for early-stage AD diagnosis and intervention.


Assuntos
Doença de Alzheimer/terapia , Nanopartículas Magnéticas de Óxido de Ferro/química , Receptores Depuradores/química , Anticorpos de Cadeia Única/química , Doença de Alzheimer/diagnóstico , Amiloide , Peptídeos beta-Amiloides/farmacologia , Animais , Encéfalo/patologia , Citocinas , Cinética , Masculino , Camundongos , Camundongos Transgênicos , Microglia , Fragmentos de Peptídeos/farmacologia , Fagocitose
17.
Int J Nanomedicine ; 15: 4919-4932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764925

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Diagnosing AD before symptoms arise will facilitate earlier intervention. The early diagnostic approaches are thus urgently needed. METHODS: The multifunctional nanoparticles W20/XD4-SPIONs were constructed by the conjugation of oligomer-specific scFv antibody W20 and class A scavenger receptor (SR-A) activator XD4 onto superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs' stability and uniformity in size were measured by dynamic light scattering and transmission electron microscopy. The ability of W20/XD4-SPIONs for recognizing Aß oligomers (AßOs) and promoting AßOs phagocytosis was assessed by immunocytochemistry and flow cytometry analysis. The blood-brain barrier permeability of W20/XD4-SPIONs was determined by a co-culture transwell model. The in vivo probe distribution of W20/XD4-SPIONs in AD mouse brains was detected by magnetic resonance imaging (MRI). RESULTS: W20/XD4-SPIONs, as an AßOs-targeted molecular MRI contrast probe, readily reached pathological AßOs regions in brains and distinguished AD transgenic mice from WT controls. W20/XD4-SPIONs retained the property of XD4 for SR-A activation and significantly promoted microglial phagocytosis of AßOs. Moreover, W20/XD4-SPIONs exhibited the properties of good biocompatibility, high stability and low cytotoxicity. CONCLUSION: Compared with W20-SPIONs or XD4-SPIONs, W20/XD4-SPIONs show the highest efficiency for AßOs-targeting and significantly enhance AßOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AßOs in AD brains to provide an MRI signal, demonstrating that W20/XD4-SPIONs are promising diagnostic agents for early-stage AD. Due to the beneficial effect of W20 and XD4 on neuropathology, W20/XD4-SPIONs may also have therapeutic potential for AD .


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/imunologia , Imunoconjugados/química , Nanopartículas de Magnetita/química , Receptores Depuradores/metabolismo , Anticorpos de Cadeia Única/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Especificidade de Anticorpos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Diagnóstico Precoce , Imunoconjugados/farmacologia , Imageamento por Ressonância Magnética , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/patologia , Nanopartículas Multifuncionais/química , Fagocitose/efeitos dos fármacos , Anticorpos de Cadeia Única/imunologia
18.
Vaccines (Basel) ; 8(3)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630299

RESUMO

Immunotherapy focusing on reducing the amyloid-beta (Aß) burden is a promising treatment strategy for Alzheimer's disease (AD). Many clinical studies on AD immunotherapies have failed due to low safety and efficacy, calling for a highly potent AD vaccine which induces sufficient antibody titer while avoiding side effects. Here, we designed a yeast-based vaccine Y-5A15 comprising five copies of Aß1-15 displayed on the surface of yeast cell wall, and we subcutaneously immunized APP/PS1 mice three times. Our results demonstrated that the Y-5A15 remarkably enhanced the Aß epitope immunogenicity and elicited high antibody titers against Aß in AD mice. Importantly, Y-5A15 vaccination successfully reduced Aß levels, plaque burden and glial activation, rescued synaptic deficits and significantly ameliorated memory and cognitive decline in APP/PS1 transgenic mice, suggesting that the yeast-based Aß epitope vaccine has a promising potency for the treatment of AD.

19.
Int J Biol Sci ; 16(10): 1745-1752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226294

RESUMO

Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China. People's adherence to control measures is affected by their knowledge, attitudes, and practices (KAP) towards COVID-19. In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak. An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China. A self-developed online KAP questionnaire was completed by the participants. The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19. Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days. Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor. The overall correct rate of the knowledge questionnaire was 90%. The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19. Nearly all of the participants (98.0%) wore masks when going out in recent days. In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019. Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19. Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices. Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Povo Asiático , COVID-19 , China/epidemiologia , Infecções por Coronavirus/prevenção & controle , Estudos Transversais , Escolaridade , Feminino , Humanos , Modelos Logísticos , Masculino , Máscaras , Pessoa de Meia-Idade , Ocupações , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
20.
Int J Food Microbiol ; 325: 108623, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32339770

RESUMO

Salmonellosis is a challenge to public health globally, and many infections have been principally linked to the consumption of contaminated eggs. The objective of this study is to estimate the prevalence of Salmonella in commercial eggs and susceptibilities of isolates to a panel of 14 antimicrobial agents which were determined according to Clinical and Laboratory Standards Institute (CSLI) procedures. A total of 33,288 eggs (5548 pooled samples of six eggs) were collected across China in 2016 and the prevalence of Salmonella was 0.5% (27/5548). The most predominant serotype was S. enteritidis. No significant differences were observed on the basis of the egg component tested, shell condition, packaging type, sampling site or sampling season. However, there were significant differences among provincial regions. About 64.3% (n = 18) isolates were resistant to nalidixic acid, followed by ampicillin (39.3%) and ampicillin/sulbactam (39.3%). All isolates were susceptible to ceftazidime, cefalothin, ciprofloxacin, cefepime, cefotaxime, imipenem and meropenem. Three Salmonella isolates exhibited resistance to multiple antibiotics. This study provides valuable baseline data of the occurrence of Salmonella in eggs, which will be used for risk assessments of possible human foodborne infections associated with the consumption of contaminated eggs.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/fisiologia , Ovos/microbiologia , Salmonella enteritidis/efeitos dos fármacos , Animais , China/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Intoxicação Alimentar por Salmonella/epidemiologia , Infecções por Salmonella/epidemiologia , Salmonella enteritidis/isolamento & purificação
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