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1.
Nanoscale ; 13(39): 16525-16532, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34596650

RESUMO

Appropriate tuning of robust artificial coatings can not only enhance intracellular delivery but also preserve the biological functions of genetic molecules in gene based therapies. Here, we report a strategy to synthesize controllable nanostructures in situ by encapsulating CRISPR/Cas9 plasmids into metal-organic frameworks (MOFs) via biomimetic mineralization. The structure-functionality relationship studies indicate that MOF-coated nanostructures dramatically impact the biological features of the contained plasmids through different embedding structures. The plasmids are homogeneously distributed within the heterogeneous nanoarchitecture and protected from enzymatic degradation. In addition, the plasmid-MOF structure exhibits excellent loading capability, pH-responsive release, and affinity for plasmid binding. Through in vitro assays it was found that the superior MOF vector can greatly enhance cellular endocytosis and endo/lysosomal escape of sheltered plasmids, resulting in successful knock-in of GFP-tagged paxillin genomic sequences in cancer cell lines with high transfection potency compared to our previous studies. Thus, the development of new cost-effective approaches for MOF-based intracellular delivery systems offers an attractive option for overcoming the physiological barriers to CRISPR/Cas9 delivery, which shows great potential for investigating paxillin-associated focal adhesions and signal regulation.

2.
Braz J Med Biol Res ; 54(11): e11592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550275

RESUMO

Cervical cancer (CC) patients have a poor prognosis due to the high recurrence rate. However, there are still no effective molecular signatures to predict the recurrence and survival rates for CC patients. Here, we aimed to identify a novel signature based on three types of RNAs [messenger RNA (mRNAs), microRNA (miRNAs), and long non-coding RNAs (lncRNAs)]. A total of 763 differentially expressed mRNAs (DEMs), 46 lncRNAs (DELs), and 22 miRNAs (DEMis) were identified between recurrent and non-recurrent CC patients using the datasets collected from the Gene Expression Omnibus (GSE44001; training) and The Cancer Genome Atlas (RNA- and miRNA-sequencing; testing) databases. A competing endogenous RNA network was constructed based on 23 DELs, 15 DEMis, and 426 DEMs, in which 15 DELs, 13 DEMis, and 390 DEMs were significantly associated with disease-free survival (DFS). A prognostic signature, containing two DELs (CD27-AS1, LINC00683), three DEMis (hsa-miR-146b, hsa-miR-1238, hsa-miR-4648), and seven DEMs (ARMC7, ATRX, FBLN5, GHR, MYLIP, OXCT1, RAB39A), was developed after LASSO analysis. The built risk score could effectively separate the recurrence rate and DFS of patients in the high- and low-risk groups. The accuracy of this risk score model for DFS prediction was better than that of the FIGO (International Federation of Gynecology and Obstetrics) staging (the area under receiver operating characteristic curve: training, 0.954 vs 0.501; testing, 0.882 vs 0.656; and C-index: training, 0.855 vs 0.539; testing, 0.711 vs 0.508). In conclusion, the high predictive accuracy of our signature for DFS indicated its potential clinical application value for CC patients.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/genética , RNA Mensageiro , Ubiquitina-Proteína Ligases , Neoplasias do Colo do Útero/genética , Proteínas rab de Ligação ao GTP
3.
Nutrients ; 13(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34579087

RESUMO

Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.

4.
Biomaterials ; 277: 121128, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34537502

RESUMO

Intratumoral upregulated reactive oxygen species (ROS) has been extensively exploited as exclusive stimulus to activate drug release for tumor-specific therapy. However, insufficient endogenous ROS and tumor heterogeneity severely restrict clinical translation of current ROS-responsive drug delivery systems. Herein, a tailored ROS-activatable self-amplifying supramolecular nanoprodrug was developed for reinforced ROS-responsiveness and highly selective antitumor therapy. A novel ROS-cleavable CA-based thioacetal linker CASOH was synthesized with ROS generator cinnamaldehyde (CA) incorporated into its molecular structure, to skillfully realize self-amplifying positive feedback loop of "ROS-activated CA release with CA-induced ROS regeneration". CASOH was modified with a cytosine analogue gemcitabine (GEM) to obtain ROS-activatable self-immolative prodrug CAG, which could be selectively activated in tumor cells and further achieve self-boosting "snowballing" activation via ROS compensation, while keep inactive in normal cells. Through Watson-Crick nucleobase pairing (G≡C)-like hydrogen bonds, CAG efficiently crosslinked with a matched guanine-rich acyclovir-modified hyaluronic acid conjugate HA-ACV, to self-assemble into pH/ROS dual-responsive supramolecular nanoprodrug HCAG. With high stability, beneficial tumor targeting capacity and pH/ROS-responsiveness, HCAG nanoformulation exhibited remarkable in vivo antitumor efficacy with minimal systemic toxicity. Based on unique tumor-specific self-amplifying prodrug activation and Watson-Crick base pairing-inspired supramolecular self-assembly, this study provides an inspirational strategy of exploiting novel ROS-responsive nanoplatform with reinforced responsiveness and specificity for future clinical translation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34360088

RESUMO

Written vocabulary size plays a key role in children's reading development. We aim to study the relationship between Chinese written vocabulary size and cognitive, emotional, and behavioral factors in primary school students. Using stratified cluster sampling, 1162 pupils from Grade 2~5 in Guangzhou were investigated. Chinese written vocabulary size, cognitive, emotional, and behavioral factors were assessed by the Chinese written vocabulary size assessment scale, the dyslexia checklist for Chinese children (DCCC) and the Strengths and Difficulties Questionnaire (SDQ), respectively. The scores of visual word recognition deficit (ß = -3.32, 95% CI: -5.98, -0.66) and meaning comprehension deficit (ß = -6.52, 95% CI: -9.39, -3.64) were negatively associated with Chinese written vocabulary size; the score of visual word recognition deficit (odds ratio (OR) = 1.04, 95% CI: 1.02, 1.07) was the related factor of a delay in written vocabulary size. The score of meaning comprehension deficit was negatively associated with boys' Chinese written vocabulary size, while the score of auditory word recognition deficit was negatively associated with girls' Chinese written vocabulary size. The related factor of a delay in written vocabulary size was spelling deficit in boys and visual word recognition deficit in girls. There is a significant correlation between Chinese written vocabulary size and cognitive factors, but not emotional and behavioral factors in primary school students and these correlations are different when considering gender.


Assuntos
Leitura , Vocabulário , Criança , China , Compreensão , Feminino , Humanos , Masculino , Instituições Acadêmicas , Estudantes
6.
PLoS One ; 16(8): e0255527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343201

RESUMO

The objective of this study was to explore the effects of time, seasons, and total carbon (TC) on Copper (Cu) and Zinc (Zn) deposition in the surface sediments. This study was performed at the H-02 constructed wetland on the Savannah River Site (Aiken, SC, USA). Covering both warm (April-September) and cool (October-March) seasons, several sediment cores were collected twice a year from the H-02 constructed wetland cells from 2007 to 2013. Total concentrations of Cu and Zn were measured in the sediments. Concentrations of Cu and Zn (mean ± standard deviation) in the surface sediments over 7 years of operation increased from 6.0 ± 2.8 and 14.6 ± 4.5 mg kg-1 to 139.6 ± 87.7 and 279.3 ± 202.9 mg kg-1 dry weight, respectively. The linear regression model explained the behavior and the variability of Cu deposition in the sediments. On the other hand, using the generalized least squares extension with the linear regression model allowed for unequal variance and thus produced a model that explained the variance properly, and as a result, was more successful in explaining the pattern of Zn deposition. Total carbon significantly affected both Cu (p = 0.047) and Zn (p < 0.001). Time effect on Cu deposition was statistically significant (p = 0.013), whereas Zn was significantly affected by the season (p = 0.009).

7.
Adv Healthc Mater ; 10(19): e2100676, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414688

RESUMO

Due to their great stability and special cavities, metal-organic cages (MOCs) are increasingly considered as promising nanocarriers for drug delivery. However, the size and surface dilemmas restrict their further biomedical applications. The ultrasmall size of MOCs facilitates tumor penetration but suffers from quick clearance and poor accumulation at the tumor site. Hydrophobicity of MOC surfaces improves internalization into tumor cells while causing low blood circulation time as well as poor biocompatibility. Therefore, it remains challenging for the MOC-based drug delivery nanoplatform to realize high therapeutic efficacy because it requires different or even opposite dimensions and surface characteristics in different steps of circulation, penetration, accumulation, and internalization processes. In this study, an unprecedented phototriggered self-adaptive platform (ZnPc@polySCage) is developed by integrating functionalized MOCs and a photodynamic therapy based reactive oxygen species responsive strategy to realize high-efficiency tumor-specific therapy. ZnPc@polySCage remains hydrophilic and stealthy during circulation, and retains its small original size for tumor penetration, while transforming to a larger size for effective accumulation and hydrophobic for enhanced internalization under laser irradiation in tumor tissue. With these essential transitions, ZnPc@polySCage demonstrates prominent antitumor effects. Overall, the work provides an advantageous strategy for functional MOC-based platforms and biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Preparações Farmacêuticas , Fotoquimioterapia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Neoplasias/tratamento farmacológico
8.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166210, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34246751

RESUMO

BACKGROUND: The rapid and accurate discrimination of colorectal carcinoma (CRC) and polyps at the molecular level enables early intervention of CRC, which can greatly improve the 5-year survival rate of patients. Here we reported the potential of conductive polymer spray ionization mass spectrometry (CPSI-MS) in successfully screening CRC according to the serum metabolic profile. METHODS: Trace intravenous blood (50 µL) was collected from 60 colorectal carcinoma (CRC) and 60 polyp patients, respectively. After centrifugation, serum (2 µL) was loaded onto the tip of conductive polymer to form a dried serum spot. When the 5 µL methanol-water (1:1, v/v) extraction solvent was spiked onto the dried serum spot followed with +4.5 kV high voltage applied on the polymer tip, the extracted components will be ionized and carried into the MS system for direct metabolic profiling. FINDINGS: There were 51 metabolites discovered to be significantly changed in CRC serum compared to polyps. Combining these metabolites as the characteristic panel, the ideal diagnostic performance was achieved by Lasso regression model with the accuracy of 88.3%. INTERPRETATION: This pilot study demonstrated the potential of CPSI-MS as a cost-effective tool in large-scale CRC screening in the high-risk population.

9.
Adv Drug Deliv Rev ; 176: 113891, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34324887

RESUMO

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.

10.
Nutrients ; 13(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206098

RESUMO

A probiotic formulation combining Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33, and Bifidobacterium bifidum Rosell®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime® or Probiokid® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.


Assuntos
Diarreia Infantil/prevenção & controle , Probióticos/administração & dosagem , Anemia Ferropriva , Bifidobacterium bifidum , Candidíase/prevenção & controle , Criança , China , Eczema/prevenção & controle , Enterocolite/prevenção & controle , Humanos , Imunoglobulina A Secretora , Lactente
11.
Artigo em Inglês | MEDLINE | ID: mdl-34299989

RESUMO

The current worldwide state of energy scarcity and low waste utilization has led to a decrease in the supply of ecological services, something that seriously affects the development of cities. In this study, we propose an urban self-circulation design based on multiple systems within the traditional biogas, wetland, rainwater, solar power, and urban farm systems framework to achieve effective improvements in urban waste utilization and the optimization of the urban waste-energy flow cycle. Emergy conversion is used to evaluate system optimization, and the simulation results show that the novel proposed system can effectively improve urban waste utilization with an energy output rate of 3.18 × 10, an environmental load of 4.27 × 10-2, and a sustainability index of 7.45 × 102 in the core system; additionally, it can improve resource utilization of small-scale cities with an energy output rate of 1.85 × 100, an environmental load of 1.20 × 100, and a sustainability index of 1.54 × 100 in the total system. The inter-system energy flow model can significantly optimize urban energy systems based on ecological models with low-emergy resource input, including biogas systems and urban farm systems. This model can reduce the environmental load and effectively compensate for the reduced supply capacity of ecosystem services caused by urbanization, making it suitable for extension to other small-scale built environments that are relatively independent and rich in natural resources.


Assuntos
Ecossistema , Urbanização , China , Cidades , Conservação dos Recursos Naturais , Áreas Alagadas
12.
Ophthalmic Surg Lasers Imaging Retina ; 52(7): 396-399, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34309430

RESUMO

A major cause of poor visual prognosis in Coats disease is the formation of fibrovascular changes following dense foveal lipid deposition. The authors document the multimodal imaging findings of a 38-year-old woman and a 23-year-old man with adult-onset Coats disease who presented with macular edema and foveal lipid accumulation. Thermal laser targeting individual capillary macroaneurysms combined with intravitreal anti-vascular endothelial growth factor (VEGF) therapy was performed. Although there was a subsequent increase in foveal lipid immediately following the resolution of macular edema, these lipids largely resolved, leaving behind no evidence macular neovascular fibrosis. This report highlights the potential protective effect of combination therapy with thermal laser and intravitreal anti-VEGF therapy for macular exudation associated with Coats disease. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:396-399.].

13.
Nat Commun ; 12(1): 4310, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262026

RESUMO

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Macrófagos/transplante , Fotoquimioterapia/métodos , Animais , Apoptose/efeitos dos fármacos , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Indóis/administração & dosagem , Indóis/química , Indóis/farmacologia , Raios Infravermelhos , Macrófagos/química , Nanomedicina , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Oxaliplatina/administração & dosagem , Oxaliplatina/química , Oxaliplatina/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacologia
14.
J Mol Endocrinol ; 67(3): 107-119, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34270447

RESUMO

Hypothyroidism is a common endocrine disease caused by a deficiency of thyroid hormones, which could affect the hypothalamus-pituitary-gonadal (HPG) axis and cause additional severe fertility problems. However, the pathogenesis of abnormal reproductive capacity caused by hypothyroidism and whether there are differences between females and males need more study. Here, we constructed a prolonged neonatal hypothyroid rat model using 6-propyl-2-thiouracil (PTU). H&E staining and RNA-sequencing were performed to detect histopathological and transcriptome changes. Our results indicated that the numbers of ventromedial hypothalamus nuclei were increased, and the number of pituitary chromophobes was sharply increased, whereas the proportion of pituitary acidophils and pituitary basophils were obviously reduced. The differentially expressed genes of the HPG axis organs were identified, and different tissues shared similar steroid hormone and oxidative stress-related terms in gene ontology analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis indicated oxidative stress, and apoptosis-related genes were more enriched in male hypothyroid pituitaries, whereas the serum levels of growth hormone, follicle-stimulating hormone, and luteinizing hormone that were detected by ELISA were also reduced more in male hypothyroid rats, suggesting that prolonged neonatal hypothyroidism may have a more significant impact on male pituitaries. Moreover, the multi-organ oxidative stress in hypothyroid rats was confirmed by the higher expression of oxidative stress-related genes, such as the Txnip. The increased level of oxidative stress may have contributed to the histopathological and transcriptome changes of HPG axis organs in the prolonged neonatal hypothyroidism rats, especially in male pituitaries.

15.
BMC Ophthalmol ; 21(1): 267, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187398

RESUMO

BACKGROUND: Demographic, systemic and ocular factors may impact macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements. This study aimed to investigate the influences of multiple potential determinants of macular GCIPL thickness in normal Chinese adults. METHODS: This was a retrospective study conducted on 225 normal eyes from 225 healthy Chinese adults. GCIPL thickness were obtained using Cirrus high-definition optical coherence tomography (OCT). The age, gender, laterality, spherical equivalent (SE) refractive error, intraocular pressure (IOP), axial length (AL), central cornea thickness (CCT), circumpapillary retinal nerve fibre layer (pRNFL) thickness and OCT signal strength were recorded and their respective effect on GCIPL thickness parameters were evaluated. RESULTS: The mean (± SD) average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness was 84.56 ± 5.36, 81.32 ± 5.58, 83.08 ± 5.37, 85.70 ± 5.95, 87.15 ± 6.26, 85.07 ± 6.11, 82.46 ± 5.76, and 83.88 ± 5.59 µm, respectively. Determinants of thinner GCIPL thickness were older age (P = 0.001-0.117; effects enhanced if age over 40 years), thinner pRNFL (all P < 0.001), and weaker signal strength (all P < 0.001). No significant difference was found between males and females (P = 0.069-0.842), and between right eyes and the left eyes (P = 0.160-0.875) except that of superonasal GCIPL thickness (P < 0.001). There was no significant correlation between GCIPL thickness and SE, IOP, CCT, and AL (P = 0.135-0.968). CONCLUSIONS: Individual determinants associated with thinner GCIPL thickness were older age (particularly over 40 years of age), thinner pRNFL, and weaker OCT signal strength. This is relevant in comprehensively understanding the normative data and differentiating normal aging from abnormalities.


Assuntos
Fibras Nervosas , Células Ganglionares da Retina , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Pressão Intraocular , Masculino , Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica
16.
Biol Psychol ; 163: 108134, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34116087

RESUMO

The facial expression of pain is a universal social language that transcends cultures and societies. Gaining increasing popularity, emoji is now widely used to express emotional states during digital communication. Yet, it remains unclear whether emoji expression of pain can be processed as effectively as facial expression. This event-related brain potential (ERP) study investigates whether perception of pain expressions in emoji shares similarity with faces. Participants judged pain or neutral expressions in emoji and faces in a classic empathy paradigm. A dynamic convergent-divergent-convergent process was found during the observation of pain expressions. While the recognition for pain is better for faces than for emoji (both in accuracy and reaction time), we found similar P2 amplitudes during the early stage of processing and similar LPP amplitudes during later stage. Interestingly, the neural response diverges during P3 and N2 between faces and emoji: P3 respond more strongly to pain expression (relative to neutral) in faces, whereas N2 respond more strongly to pain expression (relative to neutral) in emoji. Our findings point to the commonality of perceiving pain in faces and in emoji, as well as the distinct salience of detecting pain in faces.


Assuntos
Eletroencefalografia , Emoções , Potenciais Evocados , Expressão Facial , Humanos , Dor
17.
J Cardiovasc Pharmacol ; 77(5): 642-649, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951699

RESUMO

ABSTRACT: Atherosclerosis (AS) is one of the most severe cardiovascular diseases involved in the phenotypic switching of vascular smooth muscle cells (VSMCs). Tryptanthrin is a natural product with broad biological activities. However, the effect of tryptanthrin on atherosclerotic progression is unclear. The aim of this study was to determine the role of tryptanthrin in AS and explore the potential mechanism. In vitro, primary VSMCs were stimulated with platelet-derived growth factor-BB (PDGF) to induce cell dedifferentiation. Treatment with tryptanthrin (5 µM or 10 µM) suppressed the proliferation and recovered the contractility of VSMCs in the presence of PDGF. The contractile proteins (α-smooth muscle actin, calponin, and SM22α) were increased, and the synthetic protein vimentin was decreased by tryptanthrin in PDGF-induced VSMCs. ApoE-/- mice fed with high-fat diet were used as an in vivo model of AS. Similarly, gavage administration of tryptanthrin (50 mg/kg or 100 mg/kg) attenuated VSMC phenotypic changes from a contractile to a synthetic state in aortic tissues of AS mice. The serum lipid level, atherosclerotic plaque formation, and arterial intimal hyperplasia were attenuated by tryptanthrin. Furthermore, tryptanthrin increased the expression levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) both in vitro and in vivo. Administration of compound C, an AMPK inhibitor, reversed the inhibitory effect of tryptanthrin on VSMC dedifferentiation in vitro. Thus, we demonstrate that tryptanthrin protects against AS progression through the inhibition of VSMC switching from a contractile to a pathological synthetic phenotype by the activation of AMPK/ACC pathway. It provides novel insights into AS prevention and treatment.

18.
Cell Res ; 31(7): 732-741, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34021265

RESUMO

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242-244 deletion (242-244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242-244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.


Assuntos
Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/farmacologia , COVID-19/imunologia , COVID-19/prevenção & controle , Imunidade Humoral , SARS-CoV-2/imunologia , Vacinas de Produtos Inativados/farmacologia , Animais , Anticorpos Neutralizantes/sangue , COVID-19/sangue , Vacinas contra COVID-19/imunologia , Linhagem Celular , Células HEK293 , Humanos , Modelos Moleculares , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/farmacologia
19.
BMC Genomics ; 22(1): 372, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34016054

RESUMO

BACKGROUND: Phytophthora capsici root rot (PRR) is a disastrous disease in peppers (Capsicum spp.) caused by soilborne oomycete with typical symptoms of necrosis and constriction at the basal stem and consequent plant wilting. Most studies on the QTL mapping of P. capsici resistance suggested a consensus broad-spectrum QTL on chromosome 5 named Pc.5.1 regardless of P. capsici isolates and resistant resources. In addition, all these reports proposed NBS-ARC domain genes as candidate genes controlling resistance. RESULTS: We screened out 10 PRR-resistant resources from 160 Capsicum germplasm and inspected the response of locus Pc.5.1 and NBS-ARC genes during P. capsici infection by comparing the root transcriptomes of resistant pepper 305R and susceptible pepper 372S. To dissect the structure of Pc.5.1, we anchored genetic markers onto pepper genomic sequence and made an extended Pc5.1 (Ext-Pc5.1) located at 8.35 Mb-38.13 Mb on chromosome 5 which covered all Pc5.1 reported in publications. A total of 571 NBS-ARC genes were mined from the genome of pepper CM334 and 34 genes were significantly affected by P. capsici infection in either 305R or 372S. Only 5 inducible NBS-ARC genes had LRR domains and none of them was positioned at Ext-Pc5.1. Ext-Pc5.1 did show strong response to P. capsici infection and there were a total of 44 differentially expressed genes (DEGs), but no candidate genes proposed by previous publications was included. Snakin-1 (SN1), a well-known antimicrobial peptide gene located at Pc5.1, was significantly decreased in 372S but not in 305R. Moreover, there was an impressive upregulation of sugar pathway genes in 305R, which was confirmed by metabolite analysis of roots. The biological processes of histone methylation, histone phosphorylation, DNA methylation, and nucleosome assembly were strongly activated in 305R but not in 372S, indicating an epigenetic-related defense mechanism. CONCLUSIONS: Those NBS-ARC genes that were suggested to contribute to Pc5.1 in previous publications did not show any significant response in P. capsici infection and there were no significant differences of these genes in transcription levels between 305R and 372S. Other pathogen defense-related genes like SN1 might account for Pc5.1. Our study also proposed the important role of sugar and epigenetic regulation in the defense against P. capsici.


Assuntos
Capsicum , Phytophthora , Capsicum/genética , Resistência à Doença/genética , Dissecação , Epigênese Genética , Genes vpr , Doenças das Plantas/genética
20.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2287-2297, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047132

RESUMO

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Adenina , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/toxicidade , Rim , Ratos , Tecnologia
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