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1.
Proc Natl Acad Sci U S A ; 121(27): e2322291121, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38913905

RESUMEN

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.


Asunto(s)
Altitud , Animales , Ovinos/genética , Tibet , Variación Estructural del Genoma , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Regulación de la Expresión Génica , Genoma , Aclimatación/genética
2.
Proc Natl Acad Sci U S A ; 119(13): e2121822119, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35320043

RESUMEN

SignificanceWhether sympatric speciation (SS) is rare or common is still debated. Two populations of the spiny mouse, Acomys cahirinus, from Evolution Canyon I (EC I) in Israel have been depicted earlier as speciating sympatrically by molecular markers and transcriptome. Here, we investigated SS both genomically and methylomically, demonstrating that the opposite populations of spiny mice are sister taxa and split from the common ancestor around 20,000 years ago without an allopatric history. Mate choice, olfactory receptors, and speciation genes contributed to prezygotic/postzygotic reproductive isolation. The two populations showed different methylation patterns, facilitating adaptation to their local environment. They cope with abiotic and biotic stresses, due to high solar interslope radiation differences. We conclude that our new genomic and methylomic data substantiated SS.


Asunto(s)
Aislamiento Reproductivo , Simpatría , Animales , Especiación Genética , Genoma , Israel , Murinae/genética , Simpatría/genética
3.
Proc Natl Acad Sci U S A ; 119(19): e2121819119, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35512099

RESUMEN

The phylogeny and speciation of subterranean zokors in China are unclear, as previous studies on morphology and limited molecular markers have generated conflicting results. This study unraveled the complex evolutionary history of eight zokor species in China based on de novo assembly at chromosome level and whole-genome sequencing of 23 populations. We found extensive phylogenetic discordances between nuclear and mitochondrial phylogenies, and different coalescent phylogenies, which could be explained by introgression and incomplete lineage sorting (ILS). The recent Qinghai-Tibet Plateau uplift (∼3.60 million y ago; Mya) drove Eospalax to speciate into clade A and clade B (∼3.22 Mya), and discordant phylogenies in this node were mainly attributed to introgression rather than ILS. Clade A rapidly diverged into three lineages due to geographical isolation and glaciation, while glaciation and C4 plant expansion contributed to the speciation of clade B. ILS contributed to the discordances of two rapidly radiated nodes rather than introgression. The effective population sizes (Ne's) of all the species of Eospalax were affected by three glaciations. Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of all the species pairs. Positively selected genes putatively related to specific inhabitation adaptations were identified, such as heart development, neurogenesis, DNA repair, and immune response. Climate, geological tectonism, and C4 vegetation shaped the adaptation and speciation of zokors in China.


Asunto(s)
Genoma , Roedores , Animales , China , Genómica , Filogenia , Roedores/genética , Tibet
4.
J Med Internet Res ; 26: e47017, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557504

RESUMEN

The mortality rate in intensive care units (ICUs) is notably high, with patients often relying on surrogates for critical medical decisions due to their compromised state. This paper provides a comprehensive overview of eHealth. The challenges of applying eHealth tools, including economic disparities and information inaccuracies are addressed. This study then introduces eHealth literacy and the assessment tools to evaluate users' capability and literacy levels in using eHealth resources. A clinical scenario involving surrogate decision-making is presented. This simulated case involves a patient with a hemorrhagic stroke who has lost consciousness and requires medical procedures such as tracheostomy. However, due to the medical surrogate's lack of familiarity with eHealth devices and limited literacy in using eHealth resources, difficulties arise in assisting the patient in making medical decisions. This scenario highlights challenges related to eHealth literacy and solution strategies are proposed. In conclusion, effective ICU decision-making with eHealth tools requires a careful balance between efficiency with inclusivity. Tailoring communication strategies and providing diverse materials are essential for effective eHealth decision resources in the ICU setting. Health professionals should adopt a patient-centered approach to enhance the decision-making experience, particularly for individuals with limited eHealth literacy.


Asunto(s)
Alfabetización en Salud , Telemedicina , Humanos , Toma de Decisiones , Unidades de Cuidados Intensivos , Comunicación , Personal de Salud
5.
Pestic Biochem Physiol ; 201: 105879, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685245

RESUMEN

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.


Asunto(s)
Insecticidas , Larva , Oxazinas , Semicarbazonas , Spodoptera , Animales , Spodoptera/efectos de los fármacos , Spodoptera/crecimiento & desarrollo , Insecticidas/toxicidad , Insecticidas/farmacología , Semicarbazonas/farmacología , Larva/efectos de los fármacos , Oxazinas/toxicidad , Longevidad/efectos de los fármacos , Fertilidad/efectos de los fármacos , Inactivación Metabólica
6.
Chem Biodivers ; 21(2): e202301383, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38212902

RESUMEN

Herba Epimedii is widely used to promote bone healing, and their active ingredients are total flavonoids of Epimedium (TFE). Ras homolog gene family member A / Rho-associated protein kinase (RhoA/Rock), an important pathway regulating the cytoskeleton, has been proven to affect bone formation. However, whether TFE promotes bone healing via this pathway remains unclear. In this study, the therapeutic effects of TFE were estimated using micro-computed tomography and hematoxylin and eosin staining of pathological sections. F-actin in osteoblasts was stained to investigate the protective effects of TFE on the cytoskeleton. Its regulatory effects on the RhoA/Rock1 pathway were explored using RT-qPCR and Western blot analysis. Besides, flow cytometry, alkaline phosphatase and nodule calcification staining were performed to evaluate the effects on osteogenesis. The bone healing in rats was improved, the cytoskeletal damage in osteoblasts was reduced, the RhoA/Rock1 pathway was downregulated, and osteogenesis was enhanced after TFE treatment. Thus, TFE can promote bone formation at least partially by regulating the expression of key genes and proteins in the cytoskeleton. The findings of this study provided evidence for clinical applications and would contribute to a better understanding of Epimedium's mechanisms in treating bone defects.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas , Animales , Microtomografía por Rayos X , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Osteogénesis , Citoesqueleto
7.
Opt Express ; 31(23): 38878-38890, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38017980

RESUMEN

The traditional measurement method can't achieve real-time monitoring of soil moisture content (SMC) within a two-dimensional area. To solve the above problems, we propose a rapid SMC monitoring method for two-dimensional area based on distributed acoustic sensing (DAS). DAS demodulates the backward Rayleigh scattering signal containing seismic wave sound velocity information from the active seismic source. The folding ruler approximation is employed to calculate the sound velocity of the soil, which is then inverted to determine the soil moisture content. The experiment measured the soil within a two-dimensional area formed by the seismic source and the acoustic sensing optical cable. The sensing optical cable and the active seismic source are organized into a two-dimensional area and the measurement range is 3 × 10 m with 33 points. The SMC ranges from 15% to 40%. The experiment shows that the absolute error between the measured values obtained by DAS and the water cut meter is 7%. This experiment verifies the feasibility of using the Rayleigh scattering properties to invert SMC and provides a new method for real-time monitoring of SMC in a large area.

8.
Mov Disord ; 38(6): 978-989, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37023261

RESUMEN

BACKGROUND: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. METHODS: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. RESULTS: In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. CONCLUSIONS: We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.


Asunto(s)
Enfermedad de Machado-Joseph , Humanos , Enfermedad de Machado-Joseph/diagnóstico por imagen , Pirrolidinas , Tomografía de Emisión de Positrones/métodos , Ataxia , Glicoproteínas de Membrana/genética , Proteínas del Tejido Nervioso
9.
Proc Natl Acad Sci U S A ; 117(51): 32499-32508, 2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-33277437

RESUMEN

Speciation mechanisms remain controversial. Two speciation models occur in Israeli subterranean mole rats, genus Spalax: a regional speciation cline southward of four peripatric climatic chromosomal species and a local, geologic-edaphic, genic, and sympatric speciation. Here we highlight their genome evolution. The five species were separated into five genetic clusters by single nucleotide polymorphisms, copy number variations (CNVs), repeatome, and methylome in sympatry. The regional interspecific divergence correspond to Pleistocene climatic cycles. Climate warmings caused chromosomal speciation. Triple effective population size, Ne , declines match glacial cold cycles. Adaptive genes evolved under positive selection to underground stresses and to divergent climates, involving interspecies reproductive isolation. Genomic islands evolved mainly due to adaptive evolution involving ancient polymorphisms. Repeatome, including both CNV and LINE1 repetitive elements, separated the five species. Methylation in sympatry identified geologically chalk-basalt species that differentially affect thermoregulation, hypoxia, DNA repair, P53, and other pathways. Genome adaptive evolution highlights climatic and geologic-edaphic stress evolution and the two speciation models, peripatric and sympatric.


Asunto(s)
Evolución Biológica , Spalax/genética , Simpatría , Adaptación Biológica , Animales , Variaciones en el Número de Copia de ADN , Epigénesis Genética , Evolución Molecular , Flujo Génico , Variación Genética , Genética de Población , Genoma , Israel , Desequilibrio de Ligamiento , Masculino , Polimorfismo de Nucleótido Simple , Aislamiento Reproductivo , Spalax/fisiología
10.
Chem Biodivers ; 20(3): e202200991, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36650717

RESUMEN

In this study, the electronic nose and GC/MS were used to analyze the chemical components of essential oils from different germplasm resources of Artemisia argyi Folium (A. argyi), in order to quickly identify essential oils of A. argyi from different germplasm resources and clarify the differences among different A. argyi samples. The essential oils of A. argyi were extracted by steam distillation. This article describes for the first time that electronic nose combined with chemometrics can distinguish the essential oils of A. argyi from different germplasm, which proves the reliability and potential of this technology. GC/MS was used to identify 134 volatile components from the essential oil of A. argyi. The main bioactive components were cineole, thujarone, artemisia ketone, ß-caryophyllene, (-)-4-terpinol, 3,3,6-trimethyl-1,5-heptadien-4-ol, (-)-α-thujone, camphor, borneol. In addition, the results of principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed that there were significant differences in the essential oils of A. argyi from different germplasm resources, terpenes, alcohols and ketones played an important role in identifying the essential oils of A. argyi from different germplasm resources. This indicates that electronic nose and GC/MS combined with chemometrics can be used as reliable techniques to identify different germplasm resources of A. argyi, and provide certain reference value for quality evaluation, selection of high-quality varieties and rational development of resources of A. argyi.


Asunto(s)
Artemisia , Aceites Volátiles , Artemisia/química , Quimiometría , Nariz Electrónica , Aceites Volátiles/química , Reproducibilidad de los Resultados
11.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1194-1202, 2023 Mar.
Artículo en Zh | MEDLINE | ID: mdl-37005803

RESUMEN

Ionic liquids(ILs) are salts composed entirely of anions and cations in a liquid state at or near room temperature, which have a variety of good physicochemical properties such as low volatility and high stability. This paper mainly reviewed the research overview of ILs in the application of traditional Chinese medicine(TCM) volatile oil preparation technology. Firstly, it briefly introduced the application of TCM volatile oil preparation technology and composition classification and physicochemical properties of ILs, and then summarized the application of ILs in the extraction, separation, analysis, and preparation of TCM volatile oil. Finally, the problems and challenges of ILs in the application of TCM volatile oil were explained, and the application of ILs in TCM volatile oil in the future was prospected.


Asunto(s)
Productos Biológicos , Líquidos Iónicos , Aceites Volátiles , Cationes , Líquidos Iónicos/química , Medicina Tradicional China , Aceites Volátiles/análisis , Tecnología
12.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5540-5547, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-38114146

RESUMEN

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.


Asunto(s)
Polisorbatos , Pueraria , Polisorbatos/química , Flavonoides , Tensoactivos/química , Etanol , Emulsiones , Tamaño de la Partícula , Solubilidad
13.
J Biol Chem ; 296: 100255, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33837736

RESUMEN

T lymphocytes discriminate between healthy and infected or cancerous cells via T-cell receptor-mediated recognition of peptides bound and presented by cell-surface-expressed major histocompatibility complex molecules (MHCs). Pre-T-cell receptors (preTCRs) on thymocytes foster development of αßT lymphocytes through their ß chain interaction with MHC displaying self-peptides on thymic epithelia. The specific binding of a preTCR with a peptide-MHC complex (pMHC) has been identified previously as forming a weak affinity complex with a distinct interface from that of mature αßTCR. However, a lack of appropriate tools has limited prior efforts to investigate this unique interface. Here we designed a small-scale linkage screening protocol using bismaleimide linkers for determining residue-specific distance constraints between transiently interacting protein pairs in solution. Employing linkage distance restraint-guided molecular modeling, we report the oriented solution docking geometry of a preTCRß-pMHC interaction. The linkage model of preTCRß-pMHC complex was independently verified with paramagnetic pseudocontact chemical shift (PCS) NMR of the unlinked protein mixtures. Using linkage screens, we show that the preTCR binds with differing affinities to peptides presented by MHC in solution. Moreover, the C-terminal peptide segment is a key determinant in preTCR-pMHC recognition. We also describe the process for future large-scale production and purification of the linked constructs for NMR, X-ray crystallography, and single-molecule electron microscopy studies.


Asunto(s)
Antígenos de Superficie/ultraestructura , Unión Proteica/genética , Receptores de Antígenos de Linfocitos T/ultraestructura , Linfocitos T/ultraestructura , Antígenos de Superficie/química , Antígenos de Superficie/genética , Humanos , Complejo Mayor de Histocompatibilidad/genética , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/ultraestructura , Resonancia Magnética Nuclear Biomolecular , Péptidos/química , Péptidos/genética , Dominios y Motivos de Interacción de Proteínas/genética , Receptores de Antígenos de Linfocitos T/química , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/química , Receptores de Antígenos de Linfocitos T alfa-beta/ultraestructura , Linfocitos T/química , Linfocitos T/inmunología , Timocitos/química , Timocitos/ultraestructura
14.
Cerebellum ; 21(3): 358-367, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34264505

RESUMEN

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P < 0.05). Reduced volumes in cerebellum were also found in presymptomatic carriers. Resting-state functional MRI (R-fMRI) found reduced ReHo values in left cerebellar posterior lobule (corrected P < 0.05). Diffusion tensor imaging (DTI) demonstrated a reduction of FA values in cerebellum, midbrain, superior and inferior cerebellar peduncle (corrected P < 0.05). MRS found reduced NAA/Cr values in cerebellar vermis and hemisphere (corrected P < 0.05). Our findings could provide new insights into management of SCA36 patients. Detailed auxiliary examination are recommended to assess hearing or peripheral nerve impairment, and we should pay more attention to eye movement and cognitive changes in patients. Furthermore, for the first time, our multimodel neuroimaging evaluation generate a full perspective of brain function and structure in SCA36 patients.


Asunto(s)
Imagen de Difusión Tensora , Ataxias Espinocerebelosas , Cerebelo , Humanos , Imagen por Resonancia Magnética , Linaje , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genética
15.
Zhongguo Zhong Yao Za Zhi ; 47(3): 603-610, 2022 Feb.
Artículo en Zh | MEDLINE | ID: mdl-35178942

RESUMEN

Essential oils from Chinese medicine are popular in the fields such as medicine, food, and cosmetics because of their unique biological characteristics. However, since essential oils are lipophilic compounds with high volatility, poor stability, and strong irritation, various preparation technologies need to be employed to improve stability, reduce irritation, and increase bioavailability. At present, a variety of preparation technologies have been applied to the encapsulation of essential oils. Various encapsulation strategies are formed because of different delivery systems featured with multiple principles and characteristics and are widely used to improve the stability of essential oils. Essential oils of Chinese medicine are widely used in the medical field, and they are under continuous innovation and development in clinical research, the pharmaceutical industry, medical products, etc. The present study summarized various delivery systems that could improve the stability of essential oils and reviewed the applications of essential oils encapsulated in the delivery systems in the medical field to provide re-ferences for the improvement of stability of essential oils and their safety, efficiency, and wide use in the medical field.


Asunto(s)
Aceites Volátiles , China
16.
Ann Neurol ; 88(6): 1132-1143, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32939785

RESUMEN

OBJECTIVE: A recessive biallelic repeat expansion, (AAGGG)exp , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG)exp genotype was present in ~92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS. METHODS: In this study, we screened the pathogenic (AAGGG)exp repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function. RESULTS: We identified biallelic (AAGGG)exp in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG)exp /(AAAGG)exp genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG)exp in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow. INTERPRETATION: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria. ANN NEUROL 2020;88:1132-1143.


Asunto(s)
Expansión de las Repeticiones de ADN/genética , Atrofia de Múltiples Sistemas/genética , Proteína de Replicación C/genética , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo
17.
Mov Disord ; 36(1): 216-224, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32991004

RESUMEN

BACKGROUND: In polyglutamine (polyQ) disease, the investigation of the prediction of a patient's age at onset (AAO) facilitates the development of disease-modifying intervention and underpins the delay of disease onset and progression. Few polyQ disease studies have evaluated AAO predicted by machine-learning algorithms and linear regression methods. OBJECTIVE: The objective of this study was to develop a machine-learning model for AAO prediction in the largest spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) population from mainland China. METHODS: In this observational study, we introduced an innovative approach by systematically comparing the performance of 7 machine-learning algorithms with linear regression to explore AAO prediction in SCA3/MJD using CAG expansions of 10 polyQ-related genes, sex, and parental origin. RESULTS: Similar prediction performance of testing set and training set in each models were identified and few overfitting of training data was observed. Overall, the machine-learning-based XGBoost model exhibited the most favorable performance in AAO prediction over the traditional linear regression method and other 6 machine-learning algorithms for the training set and testing set. The optimal XGBoost model achieved mean absolute error, root mean square error, and median absolute error of 5.56, 7.13, 4.15 years, respectively, in testing set 1, with mean absolute error (4.78 years), root mean square error (6.31 years), and median absolute error (3.59 years) in testing set 2. CONCLUSION: Machine-learning algorithms can be used to predict AAO in patients with SCA3/MJD. The optimal XGBoost algorithm can provide a good reference for the establishment and optimization of prediction models for SCA3/MJD or other polyQ diseases. © 2020 International Parkinson and Movement Disorder Society.


Asunto(s)
Enfermedad de Machado-Joseph , Ataxias Espinocerebelosas , Edad de Inicio , China , Humanos , Enfermedad de Machado-Joseph/genética , Aprendizaje Automático , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/genética
18.
Zhongguo Zhong Yao Za Zhi ; 46(1): 206-213, 2021 Jan.
Artículo en Zh | MEDLINE | ID: mdl-33645072

RESUMEN

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1ß, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1ß, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1ß, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.


Asunto(s)
Colitis Ulcerosa , Animales , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colon , Sulfato de Dextran/uso terapéutico , Medicamentos Herbarios Chinos , Ratones , Simulación del Acoplamiento Molecular , Plasma
19.
Zhongguo Zhong Yao Za Zhi ; 45(4): 809-815, 2020 Feb.
Artículo en Zh | MEDLINE | ID: mdl-32237480

RESUMEN

The dummy template molecularly imprinted polymers not only has such characteristics of normal imprinted polymers as rapid identification, easy preparation, stable structure and multiple reuse, but also can imprint the compounds in natural products that are not suitable as direct template. Therefore, it has drawn more and more attention in the field of the study of natural products. This paper summarizes the methods for the selection of dummy template molecules by investigating the relevant literatures in the past ten years, analyzes the advantages and disadvantages of dummy template molecules in the practical application, and based on the types of natural products active ingredients, this paper is the first to review of the latest progress in extraction and separation of dummy template molecularly imprinted polymers. We believed that this paper could provide references for better applications of the dummy template molecularly imprinted polymers to extract and separate natural products.


Asunto(s)
Productos Biológicos/química , Fraccionamiento Químico , Impresión Molecular , Polímeros
20.
J Cell Physiol ; 234(8): 13693-13704, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30605240

RESUMEN

Selenium (Se) deficiency induces typical clinical and pathological changes and causes various pathological responses at the molecular level in several different chicken organs; the kidney is one of the target organs of Se deficiency. To explore the mechanisms that underlie the effects of microRNA-33-3p (miR-33-3p) on Se deficiency-induced kidney apoptosis, 60 chickens were randomly divided into two groups (30 chickens per group). We found that Se deficiency increased the expression of miR-33-3p in the chicken kidney. A disintegrin and metalloprotease domain 10 (ADAM10) was verified to be a target of miR-33-3p in the chicken kidney. The overexpression of miR-33-3p decreased the expression levels of ß-catenin, cyclinD1, T-cell factor (TCF), c-myc, survivin, and Bcl-2; it increased the expression levels of E-cadherin, Bak, Bax, and caspase-3; and it increased the number of chicken kidney cells in the G0/G1 phase. In addition, Se deficiency caused the ultrastructure of the kidney to develop apoptotic characteristics. The results of flow cytometry analysis and AO/EB staining showed that the number of apoptotic chicken kidney cells increased in the miR-33-3p mimic group. All these results suggest that Se deficiency-induced cell cycle arrest and apoptosis in vivo and in vitro in the chicken kidney via the regulation of miR-33-3p, which targets ADAM10.


Asunto(s)
Proteína ADAM10/metabolismo , Regulación de la Expresión Génica/fisiología , Riñón/metabolismo , MicroARNs/metabolismo , Selenio/deficiencia , Animales , Apoptosis/fisiología , Puntos de Control del Ciclo Celular/fisiología , Pollos , Femenino , Riñón/patología , Masculino
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