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1.
Front Immunol ; 12: 620943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815374

RESUMO

Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic strategy. Patients with allergic rhinitis (n = 6) and healthy controls (n = 6) were enrolled, and gut microbiome composition analysis was performed by 16S rDNA sequencing. We also established an ovalbumin (OVA)-induced allergic airway inflammation murine model. Dysbiosis of the gut flora was observed in both AAD patients and the mice, with the decrease of the biodiversity and the quantity of the Bacteroidetes phylum. Oral application of Bacteroides (B.) thetaiotaomicron ameliorated the symptoms of OVA-induced airway hyperresponsiveness (AHR) and attenuated the airway inflammation in mice. In addition, nasal lavage fluid (NALF) and bronchoalveolar lavage fluid (BALF) from AAD mice orally administered with B. thetaiotaomicron showed reduced numbers of immune cells, and diminished secretion of T helper (Th)-2 cytokines (IL-4, IL-5, and IL-13) compared with the corresponding control mice, whereas the levels of Th1 cytokineIFN-γ was not changed in both the groups. When B. thetaiotaomicron was co-administered with metronidazole in AAD mice, the immunomodulatory effect was weakened and the allergic inflammatory response was aggravated. The ratios of CD4+Foxp3+ cells, CD4+ICOS+ T cells, CD4+ICOS+ Foxp3+ regulatory T cells, and IL-10-expressing CD4+Foxp3+ cells were increased in lymphocytes of spleen, mesenteric, and cervical lymph nodes of AAD mice administrated with B. thetaiotaomicron. Therefore, our data indicate that oral administration of B. thetaiotaomicron effectively inhibited the development of AAD in murine model; inhibition was mediated by the activation of Tregs and inhibition of Th2 response without promoting a Th1 response.

2.
Inorg Chem ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825478

RESUMO

A novel cationic metal-organic framework composed of {Cu2(COO)4} paddle-wheel units and a tetracarboxylic viologen derivative, namely, {[Cu2(bdcbp)(H2O)2]·2NO3·2H2O}n (Cu-CMOF, H4bdcbpCl2 = 1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium dichloride), has been successfully synthesized and structurally characterized. In Cu-CMOF, the {Cu2(COO)4} unit and viologen derivative both act as four-connected nodes forming an ssb-type cationic network with 42.84 topology, in which the positive charges are distributed on the organic viologen moieties. Deeper insight of the structure indicates that the 3D architecture of Cu-CMOF can be seen as packing of a 26-faceted polyhedral cage and two cuboid cages. Notably, Cu-CMOF displays a highly efficient anion exchange ability for capture and removal of anionic pollutants. UV-vis absorption spectra and digital images demonstrate that Cu-CMOF is capable of adsorbing the dichromate anion and anionic dyes effectively, such as methyl orange (MO-), Congo red (CR2-), and New Coccine (NC3-). Meaningfully, anionic dyes (MO-, CR2-, and NC3-) can be efficiently and selectively removed by Cu-CMOF in the presence of cationic dye methylene blue (MLB+). Such behaviors of anionic pollutant adsorption and dye separation are mainly caused by an ion-exchange process facilitated by the large cavity and decentralized distribution of positive charge in Cu-CMOF.

3.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806406

RESUMO

The NAC (NAM, ATAF1/2, and CUC2) transcription factors comprise one of the largest transcription factor families in plants and play important roles in stress responses. However, little is known about the functions of potato NAC family members. Here we report the cloning of a potato NAC transcription factor gene StNAC053, which was significantly upregulated after salt, drought, and abscisic acid treatments. Furthermore, the StNAC053-GFP fusion protein was found to be located in the nucleus and had a C-terminal transactivation domain, implying that StNAC053 may function as a transcriptional activator in potato. Notably, Arabidopsis plants overexpressing StNAC053 displayed lower seed germination rates compared to wild-type under exogenous ABA treatment. In addition, the StNAC053 overexpression Arabidopsis lines displayed significantly increased tolerance to salt and drought stress treatments. Moreover, the StNAC053-OE lines were found to have higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) under multiple stress treatments. Interestingly, the expression levels of several stress-related genes including COR15A,DREB1A, ERD11, RAB18, ERF5, and KAT2, were significantly upregulated in these StNAC053-overexpressing lines. Taken together, overexpression of the stress-inducible StNAC053 gene could enhance the tolerances to both salt and drought stress treatments in Arabidopsis, likely by upregulating stress-related genes.

4.
Stem Cell Res ; 53: 102289, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33761381

RESUMO

Urine epithelial cells were harvested from a 32-year old female patient with spinocerebellar ataxia type 3 (SCA3) and reprogrammed into induced pluripotent stem cells (iPSCs) by non-integration system. The SCA3 derived iPSCs line, CSUXHi005-A, maintained 76 CAG expansions in the ATXN3 gene, was characterized by the expression of pluripotency markers and normal karyotype. The newly generated iPSCs retain the ability to differentiate into three germ layers by teratoma test, which provide an ideal tool for disease modeling, drug screening, and cellular therapy.

5.
Autophagy ; : 1-3, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33666137

RESUMO

Although it has been reported that some autophagy-related proteins could regulate the cell cycle, the function of ULK1-ATG13, the only protein kinase complex in macroautophagy/autophagy, remains unclear. We recently found that mitotic ULK1 and ATG13 are both substrates of the key cell cycle regulator CDK1-CCNB/cyclin B. CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression. Moreover, ULK1 and ATG13 double-knockout significantly inhibits cell cycle progression and tumor cell proliferation in vitro and in vivo. These findings bridge the mutual regulation between autophagic and mitotic key kinases and provide a theoretical basis for autophagy- and cell division-related diseases based on combination therapy.

6.
Stem Cell Res Ther ; 12(1): 188, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736654

RESUMO

BACKGROUND: Neural stem cell (NSC) therapy remains one of the most potential approaches for the treatment of neurological disorders. The discovery of human induced pluripotent stem cells (hiPSCs) and the establishment of hiPSC-derived human neural stem cells (hiNSCs) have revolutionized the technique of cell therapy. Meanwhile, it is often required that NSCs are stored and transported to a long distance for research or treatment purposes. Although high survival rates could be maintained, conventional methods for cell transportation (dry ice or liquid nitrogen) are inconvenient and expensive. Therefore, the establishment of a safe, affordable, and low-cost strategy to store and transport easily accessible hiPSCs and hiNSCs, with characteristics that match fetal hNSCs, is incredibly urgent. METHODS: We reprogrammed human urinary cells to iPSCs using a non-integrating, virus-free technique and differentiated the iPSCs toward iNSCs/neurospheres and neurons, under Good Manufacturing Practice (GMP)-compatible conditions. The pluripotency of iPSCs and iNSCs was characterized by a series of classical methods (surface markers, karyotype analysis, and in vitro as well as in vivo differentiation capabilities, etc.). RESULTS: Here, our results showed that we successfully generated hiNSCs/neurospheres from more available, non-invasive, and more acceptable urinary cells by a virus-free technique. Next, we demonstrated that the iNSCs differentiated into mature cerebral cortical neurons and neural networks. Interestingly, hiNSCs survived longer as neurospheres at ambient temperature (AT) than those cultured in a monolayer. Within 7 days approximately, the neural viability remained at > 80%, while hiNSCs cultured in a monolayer died almost immediately. Neurospheres exposed to AT that were placed under standard culture conditions (37 °C, 5% CO2) recovered their typical morphology, and retained their proliferation and differentiation abilities. CONCLUSIONS: In this study, we provided a simple method for the storage of NSCs as neurospheres at AT as an alternative method to more costly and inconvenient traditional methods of cryopreservation. This will enable hiNSCs to be transported over long distances at AT and facilitate the therapeutic application of NSCs as neurospheres without any further treatment.

7.
Front Public Health ; 9: 578134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748055

RESUMO

Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM). Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured. Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05). Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.

8.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1134-1140, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787107

RESUMO

To establish the method for determining non-volatile ingredients of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isochlorogenic acid A, rosmarinic acid, ferulic acid, rutin, luteoloside, isoquercitrin, hesperidin, diosmin, diosmetin, luteolin, acacetin and linarin in Menthae Haplocalycis Herba formula granules and traditional herbal pieces by UPLC-MS/MS, and analyze the correlation of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces. Shim-pack GIST C_(18) column(2.1 mm×100 mm, 2 µm) was adopted with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution at the flow rate of 0.4 mL·min~(-1). The column temperature was set at 35 ℃. The quantitative analysis was performed using the electrospray ionization source and the multiple reaction monitoring. The linear relationship, resolution, repeatability and recovery of the 16 chemical components all met the requirements. The 16 non-volatile ingredients in traditional herbal pieces of Menthae Haplocalycis Herba could be tracked in formula granules. There were certain differences of the 16 chemical components among Menthae Haplocalycis Herba formula granules of different manufacturers and traditional herbal pieces of different producing areas. The UPLC-MS/MS method was simple, rapid and accurate, and could be used for the quality control of non-volatile ingredients in Menthae Haplocalycis Herba formula granules and traditional herbal pieces.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Correlação de Dados
9.
Nat Commun ; 12(1): 1147, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608519

RESUMO

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.


Assuntos
/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Modelos Teóricos , Pandemias/prevenção & controle , Número Básico de Reprodução , Busca de Comunicante , Humanos , Funções Verossimilhança , Máscaras , Quarentena
10.
Arch Virol ; 166(3): 789-799, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33459883

RESUMO

Hepatitis A virus (HAV), a unique hepatotropic human picornavirus, is the causative agent of acute hepatitis A in humans. Some studies have shown that HAV antagonizes the innate immune response by disrupting interferon-beta (IFN-ß) signaling by viral proteins. However, whether microRNAs (miRNAs), a class of non-coding RNAs, are involved in the antagonism of IFN-ß induction upon HAV infection is still unclear. In this study, we investigated the effects and mechanisms by which HAV-induced miRNAs antagonize IFN-ß signaling. A variety of analytical methods, including miRNA microarray, RT-qPCR, dual-luciferase reporter assay, and Western blotting, were performed using HAV-infected cells. The results indicated that HAV infection upregulates the expression of hsa-miR-146a-5p, which in turn partially suppresses the induction of IFN-ß synthesis, thereby promoting viral replication. Mechanistically, TRAF6 (TNF receptor-associated factor 6), a key adaptor protein in the RIG-I/MDA5-mediated IFN-I signaling pathway, is targeted and degraded by hsa-miR-146a-5p. As TRAF6 is necessary for IFN-ß induction, inhibition of this protein attenuates IFN-ß signaling. Taken together, the results from this study indicated that HAV disrupts RIG-I/MDA5-mediated IFN-I signaling partially through the cleavage of the essential adaptor molecule TRAF6 via hsa-miR-146a-5p.


Assuntos
Vírus da Hepatite A Humana/crescimento & desenvolvimento , Interferon gama/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/genética , Linhagem Celular , Regulação da Expressão Gênica , Hepatite A/patologia , Vírus da Hepatite A Humana/genética , Humanos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Replicação Viral
11.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33431650

RESUMO

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.


Assuntos
Busca de Comunicante , Máscaras , /epidemiologia , Humanos
12.
Nat Commun ; 12(1): 385, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452266

RESUMO

Chemically synthesized metal nanowires are promising building blocks for next-generation photonic integrated circuits, but technological implementation in monolithic integration will be severely hampered by the lack of controllable and precise manipulation approaches, due to the strong adhesion of nanowires to substrates in non-liquid environments. Here, we demonstrate this obstacle can be removed by our proposed earthworm-like peristaltic crawling motion mechanism, based on the synergistic expansion, friction, and contraction in plasmon-driven metal nanowires in non-liquid environments. The evanescently excited surface plasmon greatly enhances the heating effect in metal nanowires, thereby generating surface acoustic waves to drive the nanowires crawling along silica microfibres. Advantages include sub-nanometer positioning accuracy, low actuation power, and self-parallel parking. We further demonstrate on-chip manipulations including transporting, positioning, orientation, and sorting, with on-situ operation, high selectivity, and great versatility. Our work paves the way to realize full co-integration of various functionalized photonic components on single chips.

13.
Neuropeptides ; 86: 102125, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33486279

RESUMO

AIMS: Spinal cord injury (SCI) can cause a variety of cells apoptosis, neurodegeneration, and eventually permanent paralysis. This study aimed to examine whether transplanting human umbilical cord mesenchymal stem cells (hucMSCs) can promote locomotor function recovery, reduce apoptosis and inhibit demyelination in SCI models. MAIN METHODS: Rats were allocated into Sham group (spinal cord exposure only), SCI + PBS group (spinal cord impact plus phosphate-buffered saline (PBS) injections), SCI + hucMSCs group (spinal cord impact plus hucMSCs injections) groups. Behavioral tests, Basso-Beattie-Bresnahan locomotion scores (BBB scores), were carried out at 0, 3, 7, 14, 21, 28 days after SCI surgery. Hematoxylin-eosin staining observed spinal cord morphology. Nissl staining detected the number of nissl bodies. Myelin basic protein (MBP) and oligodendrocyte (CNPase) were examed by immunohistochemical staining. The apoptosis of oligodendrocyte and neurons were detected by immunofluorescence. RESULTS: The 28-day behavioral test showed that the BBB score of rats in the SCI + hucMSCs group increased significantly, comparing to the SCI + PBS group. The numbers of nissl bodies and myelin sheath in the damaged area of SCI + hucMSCs group were also significantly increased compared to the SCI + PBS group. HucMSCs transplanting decreased the expression of protein level of Caspase-3 and Bax and increased the Bcl-2, MBP and CNPase, rescued the apoptosis of neurons and the oligodendrocyte. CONCLUSION: These results showed that hucMSCs can improve motor function, tissue repairing and reducing apoptosis in SCI rats.

15.
ACS Biomater Sci Eng ; 7(2): 772-786, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33411504

RESUMO

Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague-Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.

16.
Chemosphere ; 265: 129140, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310317

RESUMO

People typically spend most of their time indoors. It is of importance to establish prediction models to estimate PM2.5 concentration in indoor environments (e.g., residential households) to allow accurate assessments of exposure in epidemiological studies. This study aimed to develop models to predict PM2.5 concentration in residential households. PM2.5 concentration and related parameters (e.g., basic information about the households and ventilation settings) were collected in 116 households during the winter and summer seasons in Hong Kong. Outdoor PM2.5 concentration at households was estimated using a land-use regression model. The random forest machine learning algorithm was then applied to develop indoor PM2.5 prediction models. The results show that the random forest model achieved a promising predictive accuracy, with R2 and cross-validation R2 values of 0.93 and 0.65, respectively. Outdoor PM2.5 concentration was the most important predictor variable, followed in descending order by the household marked number, outdoor temperature, outdoor relative humidity, average household area and air conditioning. The external validation result using an independent dataset confirmed the potential application of the random forest model, with an R2 value of 0.47. Overall, this study shows the value of a combined land-use regression and machine learning approach in establishing indoor PM2.5 prediction models that provide a relatively accurate assessment of exposure for use in epidemiological studies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Hong Kong , Humanos , Aprendizado de Máquina , Tamanho da Partícula , Material Particulado/análise , Estações do Ano
17.
Biosensors (Basel) ; 10(12)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321741

RESUMO

Cross-border pathogens such as the African swine fever virus (ASFV) still pose a socio-economic threat. Cheaper, faster, and accurate diagnostics are imperative for healthcare and food safety applications. Currently, the discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has paved the way for the diagnostics based on Cas13 and Cas12/14 that exhibit collateral cleavage of target and single-stranded DNA (ssDNA) reporter. The reporter is fluorescently labeled to report the presence of a target. These methods are powerful; however, fluorescence-based approaches require expensive apparatuses, complicate results readout, and exhibit high-fluorescence background. Here, we present a new CRISPR-Cas-based approach that combines polymerase chain reaction (PCR) amplification, Cas12a, and a probe-based lateral flow biosensor (LFB) for the simultaneous detection of seven types of ASFV. In the presence of ASFVs, the LFB responded to reporter trans-cleavage by naked eyes and achieved a sensitivity of 2.5 × 10-15 M within 2 h, and unambiguously identified ASFV from swine blood. This system uses less time for PCR pre-amplification and requires cheaper devices; thus, it can be applied to virus monitoring and food samples detection.

18.
Stem Cell Res ; 49: 102058, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33189042

RESUMO

Severe mycological epilepsy of infancy is a catastrophic disease with preferential dysfunction of interneurons, frequentepisoderate, cognitive and sudden death. The disease is mainly caused by heterozygous loss-of-function mutation of SCN1A gene encoding α subunit of the sodium channel Nav1.1. To generate mutations in normal iPSC, Transcription activator-like effector nucleases was used to introduce the epilepsy-causing mutation A5768G into the endogenous locus of SCN1A gene. The gene editing induced pluripotent stem cell line and normal iPSC were obtained from the same donor to eliminate significantly the genetic background noise.

19.
BMC Public Health ; 20(1): 1657, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148225

RESUMO

BACKGROUND: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ). METHODS: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven's Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ. RESULTS: The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (ß = - 4.965, 95% CI: - 9.198, - 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children's IQ scores (95% CI: - 19.2, - 3.5, P = 0.005). CONCLUSIONS: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.

20.
Biochem Pharmacol ; 183: 114299, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33148504

RESUMO

Cisplatin (CDDP)-induced acute kidney injury (AKI) limits the therapeutic use of CDDP, which urgently needs to be addressed. Our previous study demonstrated that astragaloside IV (AS IV), an active compound of the traditional Chinese herb Astragalus membranaceus, alleviated CDDP-induced AKI. To explore the mechanism, we performed a metabolomics study to explore the altered metabolic pathways and screen for sensitive biomarkers. Twenty-four rats were randomly divided into three groups, which were treated with vehicle solutions (Control), intraperitoneally injected CDDP, and intraperitoneally injected CDDP plus oral AS IV, respectively. Metabolic profiles of serum, urine, and kidney samples were analyzed by high-performance liquid chromatography-time of flight mass spectrometry. There were 38 key metabolites in the urine samples, 20 in the serum samples, and 16 in the kidney samples that were significantly altered due to AS IV-mediated protection against CDDP-induced AKI relative to CDDP-only treatment. CDDP + AS IV co-treatment significantly altered two pathways in the blood (biosynthesis of unsaturated fatty acids and alanine, aspartate, and glutamate metabolism), five pathways in the urine (phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; arginine and proline metabolism; and histidine metabolism), and five pathways in the kidneys (glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; and D-glutamine and D-glutamate metabolism). The metabolic pathways were mainly associated with improvements in inflammatory responses, oxidative stress, and energy metabolism. Adrenic acid in serum and L-histidine and L-methionine in urine were identified as sensitive biomarkers. This study provides new insights to understand the mechanism of AS IV-mediated protection against CDDP-induced AKI and has identified three candidate biomarkers to evaluate preventative treatment and assess therapeutic effectiveness.

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