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1.
Mol Psychiatry ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762692

RESUMO

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.

2.
Biomolecules ; 13(4)2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37189402

RESUMO

The gene encoding brain-derived neurotrophic factor (Bdnf) consists of nine non-coding exons driven by unique promoters, leading to the expression of nine Bdnf transcripts that play different roles in various brain regions and physiological stages. In this manuscript, we present a comprehensive overview of the molecular regulation and structural characteristics of the multiple Bdnf promoters, along with a summary of the current knowledge on the cellular and physiological functions of the distinct Bdnf transcripts produced by these promoters. Specifically, we summarized the role of Bdnf transcripts in psychiatric disorders, including schizophrenia and anxiety, as well as the cognitive functions associated with specific Bdnf promoters. Moreover, we examine the involvement of different Bdnf promoters in various aspects of metabolism. Finally, we propose future research directions that will enhance our understanding of the complex functions of Bdnf and its diverse promoters.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Esquizofrenia , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Regiões Promotoras Genéticas , Encéfalo/metabolismo , Éxons , Esquizofrenia/metabolismo
3.
Biomolecules ; 13(5)2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37238691

RESUMO

The transcripts for Bdnf (brain-derived neurotrophic factor), driven by different promoters, are expressed in different brain regions to control different body functions. Specific promoter(s) that regulates energy balance remain unclear. We show that disruption of Bdnf promoters I and II but not IV and VI in mice (Bdnf-e1-/-, Bdnf-e2-/-) results in obesity. Whereas Bdnf-e1-/- exhibited impaired thermogenesis, Bdnf-e2-/- showed hyperphagia and reduced satiety before the onset of obesity. The Bdnf-e2 transcripts were primarily expressed in ventromedial hypothalamus (VMH), a nucleus known to regulate satiety. Re-expressing Bdnf-e2 transcript in VMH or chemogenetic activation of VMH neurons rescued the hyperphagia and obesity of Bdnf-e2-/- mice. Deletion of BDNF receptor TrkB in VMH neurons in wildtype mice resulted in hyperphagia and obesity, and infusion of TrkB agonistic antibody into VMH of Bdnf-e2-/- mice alleviated these phenotypes. Thus, Bdnf-e2-transcripts in VMH neurons play a key role in regulating energy intake and satiety through TrkB pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Receptor trkB , Resposta de Saciedade , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hiperfagia/genética , Hiperfagia/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Obesidade/genética , Obesidade/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo
4.
Natl Sci Rev ; 10(3): nwad001, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37007748

RESUMO

The development of modern science and technology requires high magnetic fields exceeding 25T. Second-generation high-temperature superconducting wires, i.e. REBCO (REBa2Cu3O7-x, RE refers to Y, Gd, Dy, Eu and other rare-earth elements) coated conductors (CCs), have become the first choice for high-field magnet construction because of their high irreversible magnetic field. The mechanical stresses caused by manufacturing, thermal mismatch and Lorenz forces closely influence electromagnetic performance during operation for REBCO CCs. In addition, the recently studied screen currents have effects on the mechanical characteristics of high-field REBCO magnets. In this review, the experimental and main theoretical works on critical current degradation, delamination and fatigue, and shear investigations on REBCO CCs, are reviewed at first. Then, research progress on the screening-current effect in the development of high-field superconducting magnets is introduced. Finally, the key mechanical problems facing the future development of high-field magnets based on REBCO CCs are prospected.

5.
Natl Sci Rev ; 10(3): nwad030, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37007749

RESUMO

The inherent brittleness and low sustainability of YBa2Cu3O7 -x (YBCO) bulk superconductor seriously impede its wide applications. It is a great challenge to achieve toughening of this material and maintain its invariable superconductivity at the same time. Here, we fabricate bulk YBCO composite superconductor with a density of 2.15 g cm-3, which consists of interlocking dual network construction and shows high toughness and durability. The results show that its unit normalized fracture energy at 77 K reaches 638.6 kN m-2, which is ∼14.8 times that of YBCO bulk prepared by the top-seeded melt textured growth (TSMTG) method. Its critical current shows no degradation during the toughening process. Moreover, after 10 000 cycles, the sample does not fracture with the decay of critical current at 4 K of 14.6% whereas the TSMTG sample fractures only after 25 cycles.

6.
Nat Commun ; 14(1): 408, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697408

RESUMO

Although the electrical effects in dust storms have been observed for over 100 years, little is known about their fluctuating properties, especially for the dust concentration and electric fields. Here, using a combined observational and theoretical approach, we find that wind velocity, PM10 dust concentration, and electric fields in dust storms exhibit a universal spectrum when particle mass loading is low. In particular, all measured fields at and above 5 m display a power-law spectrum with an exponent close to - 5/3 in the intermediate-wavenumber range, consistent with the phenomenological theory proposed here. Below 5 m, however, the spectra of the wind velocity and ambient temperature are enhanced, due to the modulation of turbulence by dust particles at relatively large mass loading. Our findings reveal the electrohydrodynamic features of dust storms and thus may advance our understanding of the nonlinear processes in dust storms.

7.
Neuroendocrinology ; 113(6): 625-640, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36720204

RESUMO

INTRODUCTION: Whether central glucagon-like peptide 1 (GLP-1)/GLP-1 receptor system mediated peripheral glucose homeostasis in patients with traumatic brain injury (TBI) is not clear. We aim to determine if plasma GLP-1 level could distinguish the non-survivors from the survivors during the first 14 days after TBI that could prognose 6 months mortality. METHODS: Metabolic, inflammatory, and hematologic profiles were examined in 73 patients with TBI in neurological intensive care unit. Factors that discriminate non-survivors from survivors were determined by two-way ANOVA. Biomarkers associated with mortality were determined by binary logistic regression and Cox proportional hazard regression. RESULTS: The non-survivors had higher infectious SOFA scores (p < 0.001), lower first 3 days' body temperature (p = 0.017), greater chance of cerebral hernia (p = 0.048), and decompressive craniectomy (p = 0.001) than the survivors. Higher 14-day plasma GLP-1 (p < 0.0001), glucose (p = 0.002), and IL-6 (p = 0.005) levels, in contrast with lower insulin level at days 4-7 (p = 0.020) were found in non-survivors than in survivors. Except the survivors who had an increased 14-day platelet number (p < 0.001), the two groups did not differ in hematological profile and intestinal barrier function. Although GLP-1 correlated closely with IL-6 in both the groups, it correlated with neither insulin nor glucose in each group. GLP-1 on days 8-10 and IL-6 on days 1-3 were positively, while insulin on days 4-7 was negatively associated with mortality. CONCLUSION: Persistent higher GLP-1 level in non-survivors over the survivors may present more severe central resistance to endogenous GLP-1 in non-survivors, which may be associated with progressive hyperglycemia with increased mortality in TBI.


Assuntos
Lesões Encefálicas Traumáticas , Hiperglicemia , Humanos , Peptídeo 1 Semelhante ao Glucagon , Interleucina-6 , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Insulina , Glucose , Glicemia/metabolismo
8.
Neurocrit Care ; 38(2): 263-278, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36114315

RESUMO

BACKGROUND: Whether insulin resistance underlies deep venous thrombosis (DVT) development in patients with severe traumatic brain injury (TBI) is unclear. In this study, the association between plasma insulin levels and DVT was analyzed in patients with severe TBI. METHODS: A prospective observational study of 73 patients measured insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profiles within four preset times during the first 14 days after TBI. Ultrasonic surveillance of DVT was tracked. Two-way analysis of variance was used to determine the factors that discriminated between patients with and without DVT or with and without insulin therapy. Partial correlations of insulin level with all the variables were conducted separately in patients with DVT or patients without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcomes 6 months after TBI were assessed. RESULTS: Among patients with a mean (± standard deviation) age of 53 (± 16 years), DVT developed in 20 patients (27%) on median 10.4 days (range 4-22), with higher Acute Physiology and Chronic Health Evaluation II scores but similar Sequential Organ Failure Assessment scores and TBI severity. Patients with DVT were more likely to receive insulin therapy than patients without DVT (60% vs. 28%; P = 0.012); hence, they had higher 14-day insulin levels. However, insulin levels were comparable between patients with DVT and patients without DVT in the subgroups of patients with insulin therapy (n = 27) and patients without insulin therapy (n = 46). The platelet profile significantly discriminated between patients with and without DVT. Surprisingly, none of the coagulation profiles, blood cell counts, or inflammatory mediators differed between the two groups. Patients with insulin therapy had significantly higher insulin (P = 0.006), glucose (P < 0.001), and GLP-1 (P = 0.01) levels and were more likely to develop DVT (60% vs. 15%; P < 0.001) along with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 levels (P = 0.016). Age (P = 0.01) and elevated insulin levels at days 4-7 (P = 0.04) were independently associated with DVT. Patients with insulin therapy also showed worse Glasgow Outcome Scale scores (P = 0.001). CONCLUSIONS: Elevated insulin levels in the first 14 days after TBI may indicate insulin resistance, which is associated with platelet hyperactivity, and thus increasing the risk of DVT.


Assuntos
Lesões Encefálicas Traumáticas , Resistência à Insulina , Insulinas , Trombose Venosa , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Recém-Nascido , Prognóstico , Trombose Venosa/epidemiologia , Lesões Encefálicas Traumáticas/epidemiologia , Cuidados Críticos
9.
STAR Protoc ; 3(4): 101856, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36595927

RESUMO

Schizophrenia pathogenesis involves both genetic and environmental factors (G×E). Here, we present a protocol to prepare a schizophrenia rodent model with a specific G×E pair. We describe the breeding of Bdnf-e6-/- mice with genetic deficiency in promoter-VI-driven BDNF expression. We then detail the procedure to expose the mice to postnatal environmental stress including hypoxia, social isolation, and corticosterone. This model better represents the etiology of schizophrenia and thus may facilitate basic research and drug development for schizophrenia. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).1.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Esquizofrenia , Masculino , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/genética , Esquizofrenia/genética , Corticosterona , Modelos Animais de Doenças , Desenvolvimento de Medicamentos
10.
Nat Commun ; 12(1): 3110, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035296

RESUMO

The second generation HTS wires have been used in many superconducting components of electrical engineering after they were fabricated. New challenge what we face to is how the damages occur in such wires with multi-layer structure under both mechanical and extreme environment, which also dominates their quality. In this work, a macroscale technique combined a real-time magneto-optical imaging with a cryogenic uniaxial-tensile loading system was established to investigate the damage behavior accompanied with magnetic flux evolution. Under a low speed of tensile strain, it was found that the local magnetic flux moves gradually to form intermittent multi-stack spindle penetrations, which corresponds to the cracks initiated from substrate and extend along both tape thickness and width directions, where the amorphous phases at the tip of cracks were also observed. The obtained results reveal the mechanism of damage formation and provide a potential orientation for improving mechanical quality of these wires.

11.
Mol Cell Biochem ; 476(7): 2575-2585, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32757174

RESUMO

The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims to expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion, KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.


Assuntos
Cisplatino/farmacologia , Neoplasias Colorretais/metabolismo , Curcumina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , RNA Neoplásico/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , RNA Neoplásico/genética
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-881489

RESUMO

Objective:To analyze the epidemiological characteristics of a family and workplace clustering of COVID-19, identify the source of infection and the transmission chain, and provide evidence for prevention and control of COVID-19 pandemic. Method:Field epidemiological method was used to conduct the investigation of confirmed cases and close contacts in this cluster. Data were analyzed with descriptive method. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the novel coronavirus nucleic acid in the collected respiratory tract samples. Results:A total of 18 epidemiological related cases were collected including 16 confirmed cases and 2 cases of asymptomatic infections. The involved places included 1 beauty clinic workplace and 3 families. Seven cases were males and 11 cases were females, with the minimum, maximum and median age of 3, 65 and 32 years old, respectively. Among them, the employees attack rate was 9.80% (10/102), the family attack rate was 7.70% (5/78), and the customer attack rate was 0.58% (1/173). Positive nucleic acid test result in the respiratory tract sample of asymptomatic infection lasted for more than 2 months. Conclusions:The cause of this clustered COVID-19 epidemic is that the workplace environment is relatively closed with clustering crowds, and the source of imported infection is not discovered in time, which lead to a point-source outbreak and spread through family close contacts and clustering.

13.
Nat Commun ; 11(1): 5072, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033243

RESUMO

While the electrification of dust storms is known to substantially affect the lifting and transport of dust particles, the electrical structure of dust storms and its underlying charge separation mechanisms are largely unclear. Here we present an inversion method, which is based on the Tikhonov regularization for inverting the electric field data collected in a near-ground observation array, to reconstruct the space-charge density and electric field in dust storms. After verifying the stability, robustness, and accuracy of the inversion procedure, we find that the reconstructed space-charge density exhibits a universal three-dimensional mosaic pattern of oppositely charged regions, probably due to the charge separation by turbulence. Furthermore, there are significant linear relationships between the reconstructed space-charge densities and measured PM10 dust concentrations at each measurement point, suggesting a multi-point large-scale charge equilibrium phenomenon in dust storms. These findings refine our understanding of charge separation mechanisms and particle transport in dust storms.

14.
Mol Metab ; 31: 109-123, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918913

RESUMO

OBJECTIVE: Brown adipose tissue (BAT)-mediated thermogenesis plays a key role in energy homeostasis and the maintenance of body temperature. Previous work suggests that brain-derived neurotrophic factor (BDNF) is involved in BAT thermogenesis, but the underlying neural circuits and molecular mechanism remain largely unknown. This is in part due to the difficulties in manipulating BDNF expression in different brain regions through different promoters and the lack of tools to identify neurons in the brain specifically involved in BAT thermogenesis. METHODS: We have created several lines of mutant mice in which BDNF transcription from a specific promoter was selectively disrupted by replacing Bdnf with green fluorescent protein (GFP; Bdnf-e1, -e4, and -e6-/- mice). As such, cells expressing Bdnf-e1, -e4, or -e6 were labeled with GFP. To identify BAT-connected thermogenesis neurons in brain, we applied the retrograde pseudorabies virus labeling method from BAT. We also used chemogenetic tools to manipulate specific neurons coupled with BAT temperature recording. Moreover, we developed a new TrkB agonist antibody to rescue the BAT thermogenesis deficits. RESULTS: We show that selective disruption of Bdnf expression from promoter 1 (Bdnf-e1) resulted in severe obesity and deficits of BAT-mediated thermogenesis. Body temperature response to cold was impaired in Bdnf-e1-/- mice. BAT expression of Ucp1 and Pcg1a, genes known to regulate thermogenesis, was also reduced, accompanying a decrease in the sympathetic activity of BAT. Staining of cells expressing Bdnf-e1 transcript, combined with transsynaptic, retrograde-tracing labeling of BAT-connected neurons, identified a group of excitatory neurons in lateral hypothalamus (LH) critical for thermogenesis regulation. Moreover, an adaptive thermogenesis defect in Bdnf-e1-/- mice was rescued by injecting an agonistic antibody for TrkB, the BDNF receptor, into LH. Remarkably, activation of the excitatory neurons (VGLUT2+) in LH through chemogenetic tools resulted in a rise of BAT temperature. CONCLUSIONS: These results reveal a specific role of BDNF promoter I in thermogenesis regulation and define a small subset of neurons in LH that contribute to such regulation.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Região Hipotalâmica Lateral/metabolismo , Neurônios/metabolismo , Termogênese , Animais , Fator Neurotrófico Derivado do Encéfalo/deficiência , Fator Neurotrófico Derivado do Encéfalo/genética , Masculino , Camundongos , Camundongos Knockout , Camundongos Mutantes
15.
Acta Pharmaceutica Sinica ; (12): 335-344, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-789030

RESUMO

The objective of this research was to clone 1-deoxy-D-xylulose 5-phosphate reductoisomerase gene (MoDXR) and its promoter sequence from Morinda officinalis and carry out bioinformatic analysis, cis-acting elements analysis, and prokaryotic expression. On the basis of the MoDXR gene sequence obtained from the M. officinalis transcriptome and with NCBI-ORFfinder analysis, a pair of specific primers were designed, and used for RT-PCR amplification. The promoter region sequence at the 5′ end of MoDXR gene was isolated by the genome walking technique. Localization of MoDXR was carried out by subcellular analysis. The prokaryotic expression plasmid pET-28a-MoDXR was constructed and transfected into Escherichia coli BL21(DE3) chemically-competent cells; the recombiant plasmid expressed fusion protein after the induction by IPTG. The full-length cDNA of MoDXR was 2 015 bp,and open reading frame (ORF) size was 1 425 bp, and it encoded 474 amino acid residues and had a molecular mass of 51.27 kD. Sequence comparison with BlastP to the NCBI database revealed that MoDXR had high sequence similarity with many other DXRs, such as Coffea arabica DXR (CaDXR) and Rauvolfia verticillata DXR (RvDXR). A phylogenetic tree revealed that MoDXR had its closest relationship with DXR from Coffea arabica and Gardenia jasminoides. The subcellular localization revealed that MoDXR protein was located on the chloroplast. Plantcare analysis indicated that the promoter region sequence of MoDXR was 1 493 bp, covering multiple light, stress, and hormone-responsive cis-regulatory elements; protein electrophoresis showed that the expressed protein was the anticipated size. This research lays the foundation for further purification and structural and functional characterization of the MoDXR protein.

16.
Chin Med Sci J ; 34(3): 157-167, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601298

RESUMO

Objective Urine is a promising biomarker source for clinical proteomics studies. Regional physiological differences are common in multi-center clinical studies. In this study, we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China. Methods In this study, morning urine samples were collected from healthy urban residents in three regions of China (Haikou, Xi'an and Xining) and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions. Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database, and pathway enrichment of the differential urinary proteins was analyzed using KEGG. Results We identified 1898 proteins from Urimem samples using label-free proteome quantification, of which 56 urine proteins were differentially expressed among the three regions (P < 0.05). Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. After gender stratification, 16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples. Among these differential proteins, several proteins have been previously reported as urinary disease biomarkers. Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.


Assuntos
Proteoma/metabolismo , Urina , Adulto , Povo Asiático , Biomarcadores/urina , China , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Espectrometria de Massas em Tandem
17.
Curr Med Sci ; 39(5): 831-835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612404

RESUMO

Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The aim of this study was to investigate whether 3 Tesla SWI (3T SWI) can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism (VP), and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP. Using 3 Tesla MRI, we evaluated 38 healthy subjects, 33 patients with PD and 34 patients with VP. Two blinded readers independently assessed the images. We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP. The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls. Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP (P<0.001). The sensitivity of SWI for PD was 93.9% and the specificity was 92.1%. Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD. And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.


Assuntos
Demência por Múltiplos Infartos/diagnóstico por imagem , Imageamento por Ressonância Magnética/estatística & dados numéricos , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Demência por Múltiplos Infartos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Sensibilidade e Especificidade , Substância Negra/irrigação sanguínea , Substância Negra/patologia
18.
Nano Lett ; 19(10): 6955-6963, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31552740

RESUMO

Magnetogenetics is a new field that leverages genetically encoded proteins and protein assemblies that are sensitive to magnetic fields to study and manipulate cell behavior. Theoretical studies show that many proposed magnetogenetic proteins do not contain enough iron to generate substantial magnetic forces. Here, we have engineered a genetically encoded ferritin-containing protein crystal that grows inside mammalian cells. Each of these crystals contains more than 10 million ferritin subunits and is capable of mineralizing substantial amounts of iron. When isolated from cells and loaded with iron in vitro, these crystals generate magnetic forces that are 9 orders of magnitude larger than the forces from the single ferritin cages used in previous studies. These protein crystals are attracted to an applied magnetic field and move toward magnets even when internalized into cells. While additional studies are needed to realize the full potential of magnetogenetics, these results demonstrate the feasibility of engineering protein assemblies for magnetic sensing.


Assuntos
Ferritinas/química , Imãs/química , Animais , Cristalização , Ferritinas/genética , Células HEK293 , Humanos , Ferro/química , Campos Magnéticos , Camundongos , Engenharia de Proteínas , Células RAW 264.7
19.
Neurobiol Dis ; 132: 104590, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31470106

RESUMO

While Brain-derived Neurotrophic Factor (BDNF) has long been implicated in treating neurological diseases, recombinant BDNF protein has failed in multiple clinical trials. In addition to its unstable and adhesive nature, BDNF can activate p75NTR, a receptor mediating cellular functions opposite to those of TrkB. We have now identified TrkB agonistic antibodies (TrkB-agoAbs) with several properties superior to BDNF: They exhibit blood half-life of days instead of hours, diffuse centimeters in neural tissues instead millimeters, and bind and activate TrkB, but not p75NTR. In addition, TrkB-agoAbs elicit much longer TrkB activation, reduced TrkB internalization and less intracellular degradation, compared with BDNF. More importantly, some of these TrkB-agoAbs bind TrkB epitopes distinct from that by BDNF, and work cooperatively with endogenous BDNF. Unlike BDNF, the TrkB-agoAbs exhibit a half-life of days/weeks and diffused readily in nerve tissues. We tested one of TrkB-agoAbs further and showed that it enhanced motoneuron survival in the spinal-root avulsion model for motoneuron degeneration in vivo. Thus, TrkB-agoAbs are promising drug candidates for the treatment of neural injury.


Assuntos
Anticorpos Monoclonais/farmacologia , Neurônios Motores/efeitos dos fármacos , Degeneração Neural/patologia , Fármacos Neuroprotetores/farmacologia , Receptor trkB/agonistas , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Neurônios Motores/patologia
20.
Zhongguo Zhen Jiu ; 39(7): 703-7, 2019 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-31286730

RESUMO

OBJECTIVE: To observe the characteristics of carotid intima-media thickness (IMT) and cerebral blood flow velocity in patients with mild-to-moderate hypertension, and to evaluate the effects of acupuncture on carotid IMT and blood flow velocity of middle cerebral artery and vertebral-basilar artery. METHODS: A total of 240 patients with mild-to-moderate hypertension who met the inclusion criteria were treated with Huoxue Sanfeng acupuncture method proposed by academician SHI Xue-min. The acupoints of Renying (ST 9), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given once a day, five times a week for 3 months. The carotid ultrasonography and transcranial color Doppler were performed before treatment and 3 months after treatment to evaluate the improvements of carotid IMT and brain blood flow velocity. RESULTS: Among 175 patients, 94.3% suffered from impaired carotid IMT. After acupuncture intervention, 7.7%-10.9% patients had improved IMT but 4.6%-6.3% had aggravated carotid IMT. There was no significant difference of carotid IMT before and after treatment (P>0.05). About 50% patients had abnormal intracranial blood flow velocity; after acupuncture intervention, 27.4%-33.3% patients who had the abnormal blood flow velocity had normal one, but 27.0%-52.5% patients who had normal blood flow velocity had abnormal one. After acupuncture intervention, the low-speed blood flow of MCA, VA and BA in female patients aged 41-60 years and the low-speed blood flow of MCA and VA in female patients aged 61-70 years were significantly improved (all P<0.05); the high-speed blood flow of MCA and VA in male patients aged 61-70 years and the high-speed blood flow of VA and BA in female patients aged 41-60 years were significantly decreased (all P<0.05). CONCLUSION: Nearly 95% of patients with mild-to-moderate hypertension had carotid IMT, and about 50% had abnormal blood flow velocity of intracranial artery. The present study failed to found significant effects of acupuncture on carotid IMT, but it shows acupuncture can generally improve the low blood flow velocity in women with mild-to-moderate hypertension.


Assuntos
Terapia por Acupuntura , Hipertensão , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Espessura Intima-Media Carotídea , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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