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1.
Biosens Bioelectron ; 264: 116677, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39159587

RESUMEN

Rapid and accurate diagnostic methods are crucial for managing viral gastroenteritis in children, a leading cause of global childhood morbidity and mortality. This study introduces a novel microfluidic-Flap endonuclease 1 (FEN1)-assisted isothermal amplification (MFIA) method for simultaneously detecting major viral pathogens associated with childhood diarrhea-rotavirus, norovirus, and adenovirus. Leveraging the specificity-enhancing properties of FEN1 with a universal dspacer-modified flap probe and the adaptability of microfluidic technology, MFIA demonstrated an exceptional detection limit (5 copies/µL) and specificity in the simultaneous detection of common diarrhea pathogens in clinical samples. Our approach addresses the limitations of current diagnostic techniques by offering a rapid (turn around time <1 h), cost-effective, easy design steps (universal flap design), and excellent detection performance method suitable for multiple applications. The validation of MFIA against the gold-standard PCR method using 150 actual clinical samples showed no statistical difference in the detection performance of the two methods, positioning it as a potential detection tool in pediatric diagnostic virology and public health surveillance. In conclusion, the MFIA method promises to transform pediatric infectious disease diagnostics and contribute significantly to global health efforts combating viral gastroenteritis.


Asunto(s)
Técnicas Biosensibles , Diarrea , Endonucleasas de ADN Solapado , Norovirus , Técnicas de Amplificación de Ácido Nucleico , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Norovirus/aislamiento & purificación , Norovirus/genética , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Niño , Diarrea/virología , Diarrea/diagnóstico , Límite de Detección , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/instrumentación , Rotavirus/aislamiento & purificación , Rotavirus/genética , Sensibilidad y Especificidad , Gastroenteritis/virología , Gastroenteritis/diagnóstico
2.
Brain Behav Immun ; 122: 527-546, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39182588

RESUMEN

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by the interaction of multiple pathogenic factors. Epidemiological studies and animal experiments indicate that maternal immune activation (MIA) is closely related to the development of ASD in offspring. A large number of pro-inflammatory cytokines are transferred from the placenta to the fetal brain during MIA, which impedes fetal neurodevelopment and is accompanied by activation of immune cells and microglia. Programmed cell death protein 1 (PD-1) can be highly expressed on the surface of various activated immune cells, when combined with programmed cell death-ligand 1 (PD-L1), it can activate the PD-1/PD-L1 pathway and exert powerful immunosuppressive effects, suggesting that this immune checkpoint may have the potential to treat MIA-induced ASD. This study combined bioinformatics analysis and experimental validation to explore the efficacy of Fc-fused PD-L1 (PD-L1-Fc) in treating MIA-induced ASD. Bioinformatics analysis results showed that in human placental inflammation, IL-6 was upregulated, T cells proliferated significantly, and the PD-1/PD-L1 pathway was significantly enriched. The experimental results showed that intraperitoneal injection of poly(I:C) induced MIA in pregnant mice resulted in significant expression of IL-6 in their serum, placenta, and fetal brain. At the same time, the expression of PD-1 and PD-L1 in the placenta and fetal brain increased, CD4+ T cells in the spleen were significantly activated, and PD-1 expression increased. Their offspring mice exhibited typical ASD-like behaviors. In vitro experiments on primary microglia of offspring mice have confirmed that the expression of IL-6, PD-1, and PD-L1 is significantly increased, and PD-L1-Fc effectively reduced their expression levels. In the prefrontal cortex of MIA offspring mice, there was an increase in the expression of IL-6, PD-1, and PD-L1; activation of microglial cells, and colocalization with PD-1. Then we administered brain stereotaxic injections of PD-L1-Fc to MIA offspring mice and intraperitoneal injections to MIA pregnant mice. The results indicated that PD-L1-Fc effectively suppressed neuroinflammation in the frontal cortex of offspring mice and partially ameliorated ASD-like behaviors; MIA in pregnant mice was significantly alleviated, and the offspring mice they produced did not exhibit neuroinflammation or ASD-like behaviors. In summary, we have demonstrated the therapeutic ability of PD-L1-Fc for MIA-induced ASD, aiming to provide new strategies and insights for the treatment of ASD.


Asunto(s)
Trastorno del Espectro Autista , Antígeno B7-H1 , Placenta , Receptor de Muerte Celular Programada 1 , Animales , Femenino , Antígeno B7-H1/metabolismo , Embarazo , Receptor de Muerte Celular Programada 1/metabolismo , Ratones , Masculino , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/prevención & control , Humanos , Placenta/metabolismo , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Conducta Animal , Ratones Endogámicos C57BL , Trastorno Autístico/metabolismo , Trastorno Autístico/inmunología , Inflamación/metabolismo , Interleucina-6/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos
3.
Opt Lett ; 49(15): 4066-4069, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090860

RESUMEN

Tin-doped germanium quantum dots (Sn-doped Ge QDs)-decorated hexagonal silicon nanowires (h-Si NWs) were adopted to overcome the low infrared response of silicon and the excess dark current of germanium. High-quality Sn-doped Ge QDs with a narrow bandgap can be achieved through Ge-Sn co-sputtering on silicon nanowires by reducing the contact area between heterojunction materials and Sn-induced germanium crystallization. The absorption limit of the heterostructure is extended to 2.2 µm, and it is sensitive to 375-1550 nm light at 0 V, which has optimality at 1342 nm, with a photo-to-dark current ratio of over 815, a responsivity of 0.154 A/W, and a response time of 0.93 ms. The superior performance of the Sn-doped Ge QDs/h-Si NW photodetector in multiwavelength is attractive for multi-scenario applications.

4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 680-686, 2024 May 20.
Artículo en Chino | MEDLINE | ID: mdl-38948264

RESUMEN

Objective: To investigate the effect of empathy on depressive symptoms in adolescents and to explore the potential mediating role of family functioning in the effect of empathy on depressive symptoms. Methods: The 2022 cross-sectional data from the Chengdu Positive Child Development (CPCD) cohort were analyzed in the study. A survey was conducted in Chengdu in June 2022, involving 3020 students in grades 5-8 from three randomly selected stratified schools. The Interpersonal Reactivity Index (IRI-C), the Chinese Family Assessment Instrument (C-FAI), and the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) were used in the survey. Chi-square test or one-way analysis of variance was performed to examine the differences in various demographic characteristics (sex, grade, region, and total monthly household income) between groups of respondents, as well as the differences in family functioning, empathy, and depression. Pearson correlation coefficient was used to examine the correlation between family functioning, empathy, and depressive symptoms. Structural equation modeling and SPSS PROCESS component Model 4 were used to analyze whether family functioning played a mediating role in the effect of empathy on depressive symptoms in adolescents. Results: The detection rate of depressive symptoms among survey respondents was 25.40%. The results of the difference analysis revealed significant differences in the detection rates of depressive symptoms among respondents of different grades, regions, and monthly household incomes (P<0.05). There was no significant difference in the detection rates of depressive symptoms between male and female students. There was a significant difference in the detection rate of depressive symptoms between respondents with different scores for family dysfunction and empathy ability (P<0.001). Correlation analysis results showed that empathy scores were negatively correlated with depression (r=-0.11, P<0.001), that family dysfunction was positively correlated with depression (r=0.29, P<0.001), and that empathy scores were negatively correlated with family functioning (r=-0.37, P<0.001). The mediating role of family dysfunction in the relationship between empathy and depressive symptoms was established, with the direct effect being 0.039 (95% confidence interval [CI]: 0.010-0.069, P<0.001) and the indirect effect value being -0.096 (95% CI: -0.115--0.079, P<0.001). The direct effect value accounted for 28.89% of the total effect value, while the mediation effect value accounted for 71.11% of the total effect value. Conclusion: The empathy ability of adolescents is correlated to depressive symptoms, and family functioning plays a mediating role between empathy and depressive symptoms in adolescents. It is suggested that adolescents' empathy ability and family functioning should be enhanced through multiple channels to reduce the occurrence of depressive symptoms.


Asunto(s)
Depresión , Empatía , Humanos , Adolescente , Depresión/psicología , Masculino , Femenino , Estudios Transversales , Encuestas y Cuestionarios , Relaciones Familiares/psicología , Estudiantes/psicología , China , Familia/psicología
6.
Artículo en Inglés | MEDLINE | ID: mdl-39060517

RESUMEN

The measures to prevent COVID-19 pandemic had caused significant life changes, which may have caused stress on the mental health of children and adolescents. We aimed to evaluate the short- and long-term effects of life changes on children's mental health in a large Chinese cohort. Survey-based life changes during COVID-19 lockdown were measured among 7,829 Chinese students at Grade 1-9, including social contacts, lifestyles and family financial status. Clustering analysis was applied to identify potential patterns of these changes. Depressive and anxiety symptoms were measured using the Center for Epidemiologic Studies Depression Scale and Screen for Child Anxiety Related Emotional Disorders. Logistic regression models were used to investigate the associations between these changes, their patterns and the presence of depression/anxiety symptoms using both cross-sectional and longitudinal designs. We found that the prevalence of depression and anxiety symptoms decreased during pandemic (34.6-32.6%). However, during and shortly after lockdown, students who reported negative impacts on their study, social and outside activities, and diet had increased risks of depressive/anxiety symptoms. Decreased electronic time and sugar-sweetened consumption, as well as family income decline and unemployment, were also associated with higher risks of these symptoms. Additionally, students with changed sleep time had increased depressive symptoms. These associations attenuated or disappeared one year later. Similar patterns were observed in clustering analysis, while only the group with severe impact on family financial status showed a sustained increase in depression symptoms. In summary, restrictive measures that changed children and adolescents' daily life during COVID-19 lockdown showed negative effects on their mental health, with some commonalities and distinctions patterns in the manifestation of depression and anxiety symptoms.

7.
Nat Prod Res ; : 1-8, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38859747

RESUMEN

A new andrastin-type meroterpenoid penimerodione A (1), and three known analogues (2-4), were isolated from the culture of a marine-derived fungus Penicillium chrysogenum HNNU w0032 by the guidance of MS/MS-based molecular networking. The planar structure of 1 was established by extensive NMR spectroscopic and HRESIMS analyses, and the absolute configuration was elucidated by a single-crystal X-ray diffraction. Compound 1 showed significant inhibitory effect on NO production in LPS-stimulated BV-2 macrophages with an IC50 value of 5.9 ± 0.3 µM. The Western blot result revealed that compound 1 exerted an anti-neuroinflammatory effect via the MAPK signalling pathway.

8.
Nutrients ; 16(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38931200

RESUMEN

Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome.


Asunto(s)
Microbioma Gastrointestinal , Síndrome Metabólico , Hidrolisados de Proteína , Síndrome Metabólico/microbiología , Síndrome Metabólico/dietoterapia , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/administración & dosificación , Animales , Proteínas de Plantas
9.
J Am Chem Soc ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38843049

RESUMEN

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.

10.
Anal Chem ; 96(23): 9585-9592, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38816678

RESUMEN

The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.


Asunto(s)
Antígeno B7-H1 , Vesículas Extracelulares , Técnicas de Amplificación de Ácido Nucleico , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Biomarcadores de Tumor , Catálisis , Molécula de Adhesión Celular Epitelial/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Técnicas de Amplificación de Ácido Nucleico/métodos , Hibridación de Ácido Nucleico
11.
Diagnostics (Basel) ; 14(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38732287

RESUMEN

BACKGROUND: Patient-based real-time quality control (PBRTQC) can be a valuable tool in clinical laboratories due to its cost-effectiveness and constant monitoring. More focus is placed on discovering and improving algorithms that compliment conventional internal control techniques. The practical implementation of PBRTQC with a biochemical instrument comparison is lacking. We aim to evaluate PBRTQC's efficacy and practicality by comparing low-density lipoprotein cholesterol (LDL-C) test results to ensure consistent real-time monitoring across biochemical instrumentations in clinical laboratories. METHOD: From 1 September 2021 to 30 August 2022, the First Affiliated Hospital of Xi'an Jiaotong University collected data from 158,259 both healthy and diseased patients, including 84,187 male and 74,072 female patients, and examined their LDL-C results. This dataset encompassed a group comprising 50,556 individuals undergoing health examinations, a group comprising 42,472 inpatients (IP), and a group comprising 75,490 outpatients (OP) for the PBRTQC intelligent monitoring platform to conduct daily tests, parameter configuration, program development, real-time execution, and performance validation of the patients' data. Moreover 40 patients' LDL-C levels were assessed using two biochemical analyzers, designated as the reference and comparator instruments. A total of 160 LDL-C results were obtained from 40 both healthy and diseased patients, including 14 OP, 16 IP, and 10 health examination attendees, who were selected to represent LDL-C levels broadly. Two biochemical instruments measured LDL-C measurements from the same individuals to investigate consistency and reproducibility across patient statuses and settings. We employed exponentially weighted moving average (EWMA) and moving median (MM) methods to calculate inter-instrument bias and ensure analytical accuracy. Inter-instrument bias for LDL-C measurements was determined by analyzing fresh serum samples, different concentrations of quality control (QC), and commercialized calibrators, employing both EWMA and MM within two assay systems. The assessment of inter-instrumental bias with five different methods adhered to the external quality assessment standards of the Clinical Laboratory Center of the Health Planning Commission, which mandates a bias within ±15.0%. RESULT: We calculated inter-instrument comparison bias with each of the five methods based on patient big data. The comparison of fresh serum samples, different concentrations of QC, commercialized calibrators, and EWMA were all in the permissive range, except for MM. MM showed that the bias between two biochemical instruments in the concentration ranges of 1.5 mmoL/L-6.2 mmoL/L exceeded the permissible range. This was mainly due to the small number of specimens, affected by variations among individual patients, leading to increased false alarms and reduced effectiveness in monitoring the consistency of the inter-instrumental results. Moreover, the inter-comparison bias derived from EWMA was less than 3.01%, meeting the 15% range assessment criteria. The bias result for MM was lower than 24.66%, which was much higher than EWMA. Thus, EWMA is better than MM for monitoring inter-instrument comparability. PBRTQC can complement the use of inter-comparison bias between biochemical analyzers. EWMA has comparable inter-instrument comparability monitoring efficacy. CONCLUSIONS: The utilization of AI-based PBRTQC enables the automated real-time comparison of test results across different biochemical instruments, leading to a reduction in laboratory operating costs, enhanced work efficiency, and improved QC. This advanced technology facilitates seamless data integration and analysis, ultimately contributing to a more streamlined and efficient laboratory workflow in the biomedical field.

12.
BMC Genomics ; 25(1): 470, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745141

RESUMEN

BACKGROUND: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). RESULTS: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. CONCLUSIONS: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.


Asunto(s)
Pérdida de Heterocigocidad , Redes Neurales de la Computación , Secuenciación Completa del Genoma , Humanos , Secuenciación Completa del Genoma/métodos , Polimorfismo de Nucleótido Simple , Genoma Humano
13.
Food Chem ; 452: 139589, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744130

RESUMEN

The exopolysaccharide production from blueberry juice fermented were investigated. The highest exopolysaccharide yield of 2.2 ± 0.1 g/L (increase by 32.5 %) was reached under the conditions of temperature 26.5 °C, pH 5.5, inoculated quantity 5.4 %, and glucose addition 9.1 % using the artificial neural network and genetic algorithm. Under the optimal conditions, the viable cell counts and total acids were increased by 2.0 log CFU/mL and 1.6 times, respectively, while the content of phenolics and anthocyanin was decreased by 9.26 % and 7.86 %, respectively. The changes of these components affected the exopolysaccharide biosynthesis. The absorption bands of -OH and -CH associated with the main functional groups of exopolysaccharide were detected by Visible near-infrared spectroscopy. The prediction model based on spectrum results was constructed. Competitive adaptive reweighted sampling and the random forest were used to enhance the model's prediction performance with the value of RC = 0.936 and RP = 0.835, indicating a good predictability of exopolysaccharides content during fermentation.


Asunto(s)
Arándanos Azules (Planta) , Fermentación , Jugos de Frutas y Vegetales , Lactobacillales , Espectroscopía Infrarroja Corta , Arándanos Azules (Planta)/química , Arándanos Azules (Planta)/metabolismo , Arándanos Azules (Planta)/microbiología , Jugos de Frutas y Vegetales/análisis , Jugos de Frutas y Vegetales/microbiología , Lactobacillales/metabolismo , Lactobacillales/crecimiento & desarrollo , Polisacáridos Bacterianos/metabolismo , Polisacáridos Bacterianos/química
15.
J Transl Med ; 22(1): 446, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741170

RESUMEN

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.


Asunto(s)
Conducta Animal , Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , FN-kappa B , Transducción de Señal , Animales , Masculino , Ratones , Trastorno Autístico/genética , Trastorno Autístico/metabolismo , Trastorno Autístico/terapia , Vesículas Extracelulares/metabolismo , Inflamación/patología , Lipopolisacáridos , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/farmacología , FN-kappa B/genética , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo
16.
J Nutr Biochem ; 129: 109638, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38583499

RESUMEN

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.


Asunto(s)
Trastorno del Espectro Autista , Proteínas Nucleares , Efectos Tardíos de la Exposición Prenatal , Resveratrol , Animales , Femenino , Masculino , Ratones , Embarazo , Trastorno del Espectro Autista/inmunología , Trastorno Autístico/inducido químicamente , Trastorno Autístico/inmunología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Lipopolisacáridos/toxicidad , Ratones Endogámicos C57BL , Resveratrol/farmacología , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/inmunología , Proteínas Nucleares/metabolismo
17.
Phytomedicine ; 128: 155386, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38522317

RESUMEN

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.


Asunto(s)
Trastorno del Espectro Autista , Medicamentos Herbarios Chinos , Interleucina-17 , Metaloproteinasa 9 de la Matriz , Ratones Endogámicos C57BL , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , Interleucina-17/metabolismo , Femenino , Embarazo , Factor 6 Asociado a Receptor de TNF/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Medicamentos Herbarios Chinos/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/inducido químicamente , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Poli I-C/farmacología , Masculino , Efectos Tardíos de la Exposición Prenatal
18.
Front Neurol ; 15: 1294601, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38456154

RESUMEN

Objective: This study aims to explore the training mode for brain death determination to ensure the quality of subsequent brain death determination. Methods: A four-skill and four-step (FFT) training model was adopted, which included a clinical neurological examination, an electroencephalogram (EEG) examination, a short-latency somatosensory evoked potential (SLSEP) examination, and a transcranial Doppler (TCD) examination. Each skill is divided into four steps: multimedia theory teaching, bedside demonstration, one-on-one real or dummy simulation training, and assessment. The authors analyzed the training results of 1,577 professional and technical personnel who participated in the FFT training model from 2013 to 2020 (25 sessions), including error rate analysis of the written examination, knowledge gap analysis, and influencing factors analysis. Results: The total error rates for all four written examination topics were < 5%, at 4.13% for SLSEP, 4.11% for EEG, 3.71% for TCD, and 3.65% for clinical evaluation. The knowledge gap analysis of the four-skill test papers suggested that the trainees had different knowledge gaps. Based on the univariate analysis and the multiple linear regression analysis, among the six factors, specialty categories, professional and technical titles, and hospital level were the independent influencing factors of answer errors (p < 0.01). Conclusion: The FFT model is suitable for brain death (BD) determination training in China; however, the authors should pay attention to the professional characteristics of participants, strengthen the knowledge gap training, and strive to narrow the difference in training quality.

19.
J Biotechnol ; 385: 65-74, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38503366

RESUMEN

Ethyl carbamate (EC), a multisite carcinogenic compound, is naturally produced from urea and ethanol in alcoholic beverages. In order to reduce the content of EC in wine, the accumulation of arginine in Saccharomyces cerevisiae was regulated by genetic modifying genes involved in arginine transport and synthesis pathways to reduce the production of urea. Knockout of genes encoding arginine permease (Can1p) and amino acid permease (Gap1p) on the cell membrane as well as argininosuccinate synthase (Arg1) respectively resulted in a maximum reduction of 66.88% (9.40 µg/L) in EC, while overexpressing the gene encoding amino acid transporter (Vba2) reduced EC by 52.94% (24.13 µg/L). Simultaneously overexpressing Vba2 and deleting Arg1 showed the lowest EC production with a decrease of 68% (7.72 µg/L). The yield of total higher alcohols of the mutants all decreased compared with that of the original strain. Comprehensive consideration of flavor compound contents and sensory evaluation results indicated that mutant YG21 obtained by deleting two allele coding Gap1p performed best in must fermentation of Cabernet Sauvignon with the EC content low to 9.40 µg/L and the contents of total higher alcohols and esters of 245.61 mg/L and 41.71 mg/L respectively. This study has provided an effective strategy for reducing the EC in wine.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Vino , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Vino/análisis , Uretano/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Arginina/metabolismo , Etanol/metabolismo , Urea/metabolismo , Fermentación
20.
Front Bioeng Biotechnol ; 12: 1280363, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38532880

RESUMEN

Objective: This study aimed at quantifying the difference in kinematic and joint moments calculation for lower limbs during gait utilizing a markerless motion system (TsingVA Technology, Beijing, China) in comparison to values estimated using a marker-based motion capture system (Nokov Motion Capture System, Beijing, China). Methods: Sixteen healthy participants were recruited for the study. The kinematic data of the lower limb during walking were acquired simultaneously based on the markerless motion capture system (120 Hz) and the marker-based motion capture system (120 Hz). The ground reaction force was recorded synchronously using a force platform (1,200 Hz). The kinematic and force data were input into Visual3D for inverse dynamics calculations. Results: The difference in the lower limb joint center position between the two systems was the least at the ankle joint in the posterior/anterior direction, with the mean absolute deviation (MAD) of 0.74 cm. The least difference in measuring lower limb angles between the two systems was found in flexion/extension movement, and the greatest difference was found in internal/external rotation movement. The coefficient of multiple correlations (CMC) of the lower limb three joint moments for both systems exceeded or equaled 0.75, except for the ad/abduction of the knee and ankle. All the Root Mean Squared Deviation (RMSD) of the lower limb joint moment are below 18 N·m. Conclusion: The markerless motion capture system and marker-based motion capture system showed a high similarity in kinematics and inverse dynamic calculation for lower limbs during gait in the sagittal plane. However, it should be noted that there is a notable deviation in ad/abduction moments at the knee and ankle.

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