Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 398
Filtrar
1.
Med Image Anal ; 59: 101543, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31670139

RESUMO

Diffusion tractography in brain connectomics often involves tracing axonal trajectories across gray-white matter boundaries in gyral blades of complex cortical convolutions. To date, gyral bias is observed in most tractography algorithms with streamlines predominantly terminating at gyral crowns instead of sulcal banks. This work demonstrates that asymmetric fiber orientation distribution functions (AFODFs), computed via a multi-tissue global estimation framework, can mitigate the effects of gyral bias, enabling fiber streamlines at gyral blades to make sharper turns into the cortical gray matter. We use ex-vivo data of an adult rhesus macaque and in-vivo data from the Human Connectome Project (HCP) to show that the fiber streamlines given by AFODFs bend more naturally into the cortex than the conventional symmetric FODFs in typical gyral blades. We demonstrate that AFODF tractography improves cortico-cortical connectivity and provides highly consistent outcomes between two different field strengths (3T and 7T).

2.
Artigo em Inglês | MEDLINE | ID: mdl-31669280

RESUMO

NK-lysins, a type of broad-spectrum antimicrobial peptide (AMP), act as an essential effector of innate defense against microbial attack in higher vertebrates and so in fish. The present study delineates the structural and functional characterization of NK-lysin from yellow catfish (Pelteobagrus fulvidrac) (Pelteobagrus fulvidraco). PfNK-lysin encodes a 153-residue peptide, which displays the hallmark features of other known NK-lysins with the ordered array of six well-conserved cysteine residues and five-exon/four-intron structure. It was found to be ubiquitous in tissues, being detected most abundantly in gill and head kidney. In vivo exposure to stimuli (LPS, PolyI:C, and Edwardsiella ictaluri) induced PfNK-lysin expression in head kidney and spleen. Synthetic PfNK-lysin-derived peptide exhibited in vitro bactericidal potency against both Gram-positive and Gram-negative bacteria, with the highest inhibitory effect on pathogen Edwardsiella ictaluri. Fluorescence microscopy and scanning electron microscopy further confirmed its capacity to cause damage to the bacterial plasma membrane. Taken together, these data suggest that PfNK-lysin might participate in antimicrobial defense of yellow catfish by membrane-disruptive action.

4.
Molecules ; 24(20)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658754

RESUMO

The development of nanomaterials with special optical window is critical for clinical applications and the optoelectronic industry. In this work, eight kinds of samarium-based metal organic compound nanoparticles (Sm-Fe, Sm-Ga, Sm-Mn, Sm-Na, Sm-Nb, Sm-W, Sm-Cu, and Sm-Al) were synthesized through a solution method. They show polychromatic-photoluminescence spectra extended from the UV to near-infrared (NIR) region when excited by 280 nm, 380 nm, 480 nm, 580 nm, and 785 nm light. They emit direct white light with respect to UV excitation. Tunable white-to-green fluorescence can be achieved by variation of excitation light around 300-400 nm. When they are excited by a 785 nm light source, they show intense fluorescence around 800-1100 nm, which is promising for NIR bio-imaging. Their application in multicolor ultra-wide-range bio-tissue fluorescence imaging is demonstrated by UV (359-371 nm), blue (450-490 nm), green (540-552 nm), and NIR light (central wavelength = 785 nm) excitation with pig kidney tissue samples.

5.
Aging (Albany NY) ; 11(20): 8982-8997, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31627188

RESUMO

BACKGROUND: Increased cardiac apoptosis is a hallmark of the elderly, which in turn increases the risk for developing cardiac disease. The overexpression of Omi/HtrA2 mRNA and protein contributes to apoptosis in the aged heart. Heat shock factor 1 (HSF1) is a transcription factor that binds to the promoter of Omi/HtrA2 in the aging myocardium. However, whether HSF1 participates in cardiomyocyte apoptosis via transcriptional regulation of Omi/HtrA2 remains unclear. The present study was designed to investigate whether HSF1 plays a role in Omi/HtrA2 transcriptional regulation and myocardial apoptosis. METHODS AND RESULTS: Assessment of the hearts of mice of different ages was performed, which indicated a decrease in cardiac function reserve and an increase in mitochondrial apoptosis. Omi/HtrA2 overexpression in the elderly was negatively correlated with left ventricular function after exercise overload and positively correlated with myocardial Caspase-9 apoptosis. Chromatin immunoprecipitation (ChIP) of aging hearts and plasmid transfection/RNA interference of H9C2 cells revealed that enhancement of HSF1 expression promotes Omi/HtrA2 expression by inducing the promoter activity of Omi/HtrA2 while also increasing mitochondrial apoptosis by upregulating Omi/HtrA2 expression. CONCLUSIONS: HSF1 acts as a transcriptional factor that induces Omi/HtrA2 expression and Caspase-9 apoptosis in aged cardiomyocytes, while also decreasing cardiac function reserve.

6.
Appl Neuropsychol Adult ; : 1-8, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31646902

RESUMO

The Saint Louis University Mental Status Examination (SLUMS) has been shown to be useful in the cognitive assessment in older adults and patients with dementia. The aim of this study was to preliminarily explore the effectiveness of the Chinese version of the SLUMS in the detection of cognitive impairment in patients with traumatic brain injury (TBI) and to provide an objective basis for its clinical application in China. In this cross-sectional study, 42 patients with TBI and 30 matched normal controls were administered. Participants were assessed by the Chinese version of the Mini-Mental State Assessment scale (MMSE), Montreal Cognitive Assessment scale (MoCA) and SLUMS. Results showed that the Chinese version of the SLUMS had satisfactory internal consistency (Cronbach's α coefficient: 0.723), excellent interrater reliability (ICC: 0.990-0.998) and intrarater reliability (ICC: 0.968), as well as good validity. In the TBI group, the total SLUMS score was moderately positively correlated with the MMSE score (r = 0.702, p = .000) and highly positively correlated with the MoCA score (r = 0.831, p = .000). Receiver Operating Characteristic (ROC) curve analyses showed that the area under the curve (AUC) of the SLUMS, MMSE and MoCA were 0.872, 0.756 and 0.916, respectively. The optimal cutoff score of 22.5 or fewer points are suggested for the SLUMS to discriminate cognitive impairment, with a sensitivity of 0.844 and a specificity of 0.825. The Chinese version of the SLUMS has excellent reliability and validity, and can be used as a screening tool for cognitive impairment of patients with TBI in China.

7.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3429-3434, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602905

RESUMO

The aim of this paper was to observe the concentration,time and mechanism of autophagy induced by triptolide( TP) in ovarian granulosa cells( OGCs). CCK-8 method was used to compare the inhibitory effects of TP at different concentrations on primary cultured rat OGCs and IC50 was calculated. The effects of TP at different concentrations and time points on the expression of OGCs autophagy factor protein and the cascade of PI3 K/AKT/m TOR pathway were detected by Western blot. The effects of TP,autophagy inducer( brefeldin A) and PI3 K/m TOR inhibitor( NVP-BEZ235) on the expression of PI3 K/AKT/m TOR cascade and autophagy related factor protein were detected by Western blot. The results show that the IC50 of different concentrations of TP on OGCs of rat ovary was14. 65 µmol·L-1,and the minimum inhibitory concentration of TP was 0. 1 µmol·L-1( 100 nmol·L-1). Compared with the control group,the expression levels of beclin1 and LC3Ⅱ in each group were significantly higher than those in the control group( P<0. 05 or P<0. 01). After 12 hours of treatment with TP,brefeldin A and NVP-BEZ235,respectively,compared with the control group,TP could significantly promote the expression level of downstream autophagy effect or molecule beclin1,LC3Ⅱ and inhibit the expression level of LC3Ⅰ,p62 protein( P<0. 05 or P< 0. 01). Moreover,the expression of beclin1 and LC3Ⅱ/LC3Ⅰ in TP group was higher than that in brefeldin A group( P<0. 05 or P<0. 01),and the expression of p62 in TP group was lower than that in brefeldin A group( P<0. 05 or P<0. 01). At the same time,TP could significantly inhibit the expression of p-PI3 K,p-AKT,p-mTOR protein,and the inhibitory effect of TP was better than that of NVP-BEZ235 group. This study suggests that 100 nmol·L-1 TP could induce OGCs autophagy successfully in cultured rat ovary for 12 h; TP may induce OGCs autophagy by inhibiting PI3 k/Akt/m TOR signaling pathway.


Assuntos
Autofagia , Diterpenos/farmacologia , Células da Granulosa/efeitos dos fármacos , Fenantrenos/farmacologia , Transdução de Sinais , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Compostos de Epóxi/farmacologia , Feminino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
8.
Am J Hum Genet ; 105(5): 996-1004, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31587869

RESUMO

Mechanically activated (MA) ion channels convert physical forces into electrical signals. Despite the importance of this function, the involvement of mechanosensitive ion channels in human disease is poorly understood. Here we report heterozygous missense mutations in the gene encoding the MA ion channel TMEM63A that result in an infantile disorder resembling a hypomyelinating leukodystrophy. Four unrelated individuals presented with congenital nystagmus, motor delay, and deficient myelination on serial scans in infancy, prompting the diagnosis of Pelizaeus-Merzbacher (like) disease. Genomic sequencing revealed that all four individuals carry heterozygous missense variants in the pore-forming domain of TMEM63A. These variants were confirmed to have arisen de novo in three of the four individuals. While the physiological role of TMEM63A is incompletely understood, it is highly expressed in oligodendrocytes and it has recently been shown to be a MA ion channel. Using patch clamp electrophysiology, we demonstrated that each of the modeled variants result in strongly attenuated stretch-activated currents when expressed in naive cells. Unexpectedly, the clinical evolution of all four individuals has been surprisingly favorable, with substantial improvements in neurological signs and developmental progression. In the three individuals with follow-up scans after 4 years of age, the myelin deficit had almost completely resolved. Our results suggest a previously unappreciated role for mechanosensitive ion channels in myelin development.

9.
Stroke ; 50(11): 3101-3107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31514693

RESUMO

Background and Purpose- We aimed to systematically investigate the characteristics of cervicocranial artery dissection (CCAD) on high-resolution magnetic resonance imaging that are associated with acute ischemic stroke. Methods- Patients with CCAD were recruited and divided into stroke and nonstroke groups. The lesion location, the presence of a double lumen, intimal flap, intramural hematoma, pseudoaneurysm, irregular surface, intraluminal thrombus, and other quantitative parameters of each dissected segment were reviewed. Multiple logistic regression was used to examine the association between imaging features of CCAD and ischemic stroke. Results- A total of 145 affected vessels from 118 patients with CCAD were analyzed. Anterior circulation, intramural hematoma, irregular surface, intraluminal thrombus, and severe stenosis (>70%) on high-resolution magnetic resonance imaging were more prevalent in CCAD patient with stroke (54.4% versus 36.4%; P=0.030, 96.2% versus 84.8%; P=0.017, 74.7% versus 37.9%; P<0.001, 44.3% versus 4.5%; P<0.001, and 54.4% versus 31.8%; P=0.008, respectively). In multivariable logistic regression analysis, the presence of irregular surface and intraluminal thrombus on imaging were independently associated with acute ischemic stroke in CCAD with odds ratios of 4.29 (95% CI, 1.61-11.46, P=0.004) and 7.48 (95% CI, 1.64-34.07, P=0.009). Conclusions- The current findings supported that the presence of irregular surface and intraluminal thrombus were related to stroke occurrence in patients with CCAD. High-resolution magnetic resonance imaging might give insights into pathogenesis of ischemic stroke in CCAD. It may be useful for individual prediction of ischemic stroke early in CCAD.

10.
Oncol Rep ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31524272

RESUMO

Glioblastoma multiforme (GBM) is the most commonly occurring brain cancer, and is characterized by its poor patient outcomes. The present study examined the mRNA expression levels of the transient receptor potential melastatin (TRPM) family in various types of cancer using the ONCOMINE database, along with their corresponding expression profiles in an array of cancer cell lines based on the Cancer Cell Line Encyclopedia (CCLE) datasets. Kaplan­Meier plotter survival analysis via the Chinese Glioma Genome Atlas (CGGA) database was also used to evaluate the prognostic value of transient receptor potential melastatin 8 (TRPM8). For the activity test on the TRPM8 channel, patch­clamp recordings and Ca2+ measurements by fluorescence imaging of Fluo­4am were performed. Short hairpin RNA (shRNA) targeting TRPM8 was designed, synthesized and then transfected into the U251 cells via Lipofectamine 2000. The expression of extracellular singnal­regulated kinase (ERK), cyclin D1 and Bcl­2 were detected by performing western blotting and immunofluorescence. The apoptosis, proliferation and invasion of glioma cells were detected by using flow cytometry, and CCK­8 and Transwell invasion assays. In the present study, TRPM8 was distinctively upregulated in GBM cell lines. TRPM8 is functional and has the characteristic of outward rectification, which was verified via electrophysiology and Ca2+ fluorescence imaging in U251 cells. The western blot and immunofluorescence results revealed that the expression of ERK, cyclin D1 and Bcl­2 were decreased in the shRNA interference group. The CCK­8 assay demonstrated that the proliferation ability of U251 cells in the U251/TRPM8 group was higher than that in the U251 group and U251/Con group (P<0.05). The result of the Transwell invasion assay indicated that the invasion of human glioblastoma U251 cells was positively correlated with the expression level of TRPM8. Collectively, the results of the present study indicated that Ca2+­permeable TRPM8 nonselective cation channels contribute to survival, proliferation, apoptosis, and local tumor invasion of glioblastoma. Therefore, TRPM8 is a promising biomarker for aggressiveness of GBM, and a potential target in future anti­glioblastoma therapies.

11.
Brain ; 142(10): 3009-3027, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504254

RESUMO

N-methyl d-aspartate receptors are ligand-gated ionotropic receptors mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants in genes encoding NMDAR subunits have been associated with a spectrum of neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated GRIN2D variant in two patients with developmental and epileptic encephalopathy. GRIN2D encodes for the GluN2D subunit protein; the GluN2D amino acids affected by the variants in this report are located in the pre-M1 helix, transmembrane domain M3, and the intracellular carboxyl terminal domain. Functional analysis in vitro reveals that all six variants decreased receptor surface expression, which may underline some shared clinical symptoms. In addition the GluN2D(Leu670Phe), (Ala675Thr) and (Ala678Asp) substitutions confer significantly enhanced agonist potency, and/or increased channel open probability, while the GluN2D(Ser573Phe), (Ser1271Phe) and (Arg1313Trp) substitutions result in a mild increase of agonist potency, reduced sensitivity to endogenous protons, and decreased channel open probability. The GluN2D(Ser573Phe), (Ala675Thr), and (Ala678Asp) substitutions significantly decrease current amplitude, consistent with reduced surface expression. The GluN2D(Leu670Phe) variant slows current response deactivation time course and increased charge transfer. GluN2D(Ala678Asp) transfection significantly decreased cell viability of rat cultured cortical neurons. In addition, we evaluated a set of FDA-approved NMDAR channel blockers to rescue functional changes of mutant receptors. This work suggests the complexity of the pathological mechanisms of GRIN2D-mediated developmental and epileptic encephalopathy, as well as the potential benefit of precision medicine.

12.
Aging (Albany NY) ; 11(18): 7707-7722, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532757

RESUMO

Recent advances in single-cell RNA sequencing (scRNA-seq) have endowed researchers with the ability to detect and analyze the transcriptomes of individual cancer cells. In the present study, 16,128 tumor cells from EGFR wild-type and EGFRvIII mutant cells were profiled by scRNA-seq. Analyses of scRNA-seq data from both U87MG and U87MG-EGFRvIII libraries revealed inherent heterogeneity in gene expression and biological processes. The cells stably expressing EGFRvIII showed enhanced transcriptional activities and a relatively homogeneous pattern, which manifested as less diverse distributions, gene expression levels and functional annotations compared with those of cells expressing the nonmutated version. Moreover, the differentially expressed genes between the U87MG and U87MG-EGFRvIII groups were mainly enriched in DNA replication, DNA repair and angiogenesis. We compared scRNA-seq data with bulk RNA-seq and EGFRvIII xenograft RNA-seq data. RAD51AP1 was shown to be upregulated in all three databases. Further analysis of RAD51AP1 revealed that it is an independent prognostic factor of glioma. Knocking down RAD51AP1 significantly inhibited tumor volume in an intracranial EGFRvIII-positive GBM model and prolonged survival time. Collectively, our microfluidic-based scRNA-seq driven by a single genetic event revealed a previously unappreciated implication of EGFRvIII in the heterogeneity of GBM and identified RAD51AP1 as an oncogene in glioma.

13.
J Neuroimmunol ; 336: 577029, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31487612

RESUMO

Neuro-inflammation is widely regarded as the inflammation occurred in the central nervous system (CNS) tissue, which authentically involved in the pathogenesis such as depression although the underlying mechanism remains to be elucidated. Malva sylvestris (MS), a plant widely used in traditional medicine to mitigate urological, respiratory and oral diseases, exhibits excellent anti-oxidative and anti-inflammatory properties. In the present study, we first used LPS-induced depression-like mice to evaluate the neuro-protective effect of MS extract. We found that, after 7 days' administration of MS extract, the cognitive impairment of LPS-induced depression-like mice was efficiently alleviated, evaluated by behavioral test including the Open field, Morris water maze (MWM), Elevated plus-maze (EPM) and Rota-rod test. Furthermore, we found that MS extract also inhibited the LPS-induced neuron apoptosis and astrogliosis both in the cortex and the CA1 region of hippocampus. Finally, our findings showed that the extract of MS relieved inflammatory stress induced by LPS injury, indicated by the down-regulation of IL-1ß/6 and TNF-α, and up-regulation of IL-4 level both in vitro and in vivo. Collectively, MS extract exhibits neuro-protective activity in vivo, and therefore, it may be widely used for food to relieve the symptoms of neuro-inflammation associated disorders such as depression.

14.
Biochem Biophys Res Commun ; 519(4): 734-739, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31543347

RESUMO

AIMS: Omi/HtrA2 is a pro-apoptotic protein, increased mRNA and protein levels of Omi/HtrA2 in aging myocardium facilitates apoptosis and affects mitochondrial homeostasis. Our previous study found that p53 can bind to the Omi/HtrA2 promoter. The purpose of this study was to determine whether p53 participates in regulating the expression of Omi/HtrA2 in aging myocardium. METHODS AND RESULTS: we used Western blot to detect the expression of Omi/HtrA2 and p53 nucleoprotein, and then found that both of them were elevated in aging heart. Furthermore, we also observed the increased binding of p53 to Omi/HtrA2 promoter by chromatin immunoprecipitation. To initially explore the regulation mechanism of Omi/HtrA2, plasmid transfection and RNA interference in NIH3T3 cells were used to upregulate or knock down p53, respectively. The mRNA and protein levels of Omi/HtrA2 were increased with the overexpression of p53 by real-time PCR and Western blot, and Omi/HtrA2 promoter activity enhanced after transfected with pcDNA3.1-p53. The result from RNA interference was quite the contrary.Our study demonstrated that the binding ability of p53 to Omi/HtrA2 promoter was increased in aging myocardium, and increased p53 promoted the mRNA and protein levels of Omi/HtrA2 by enhancing the promoter activity of Omi/HtrA2. CONCLUSIONS: p53 acts as a transcriptional factor that induces Omi/HtrA2 expression in aged cardiomyocytes.These results provide a new way to explore the mechanism of increased Omi/HtrA2 in the aging process of heart.

15.
Environ Int ; 132: 105111, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476640

RESUMO

The serious fine particle (PM2.5) pollution in China causes millions of premature deaths. Driven by swift economic growth and stringent control policies, air pollutant emissions in China have changed significantly in the last decade, but the change in the source contribution of PM2.5-related health impacts remains unclear. In this study, we develop a multi-pollutant emission inventory in China for 2005-2015, and combine chemical transport modeling, ambient/household exposure evaluation and health impact assessment to quantify the contribution of eight emission sectors to PM2.5 exposure and associated health risk. From 2005 to 2015, the mortality due to PM2.5 from ambient air pollution (AAP) decreases from 1.04 (95% confidence interval, 0.84-1.25) million to 0.87 (0.70-1.04) million. The agricultural sector contributes 25% and 32% to ambient PM2.5-attributed mortality in 2005 and 2015, respectively, representing the largest contributor during this period. The contribution of power plants drops monotonously from 13% to 6%. The percentage contribution of industrial process drops significantly while the contribution of industrial combustion stays the same level. The overall contribution of industry is still as large as 26% in 2015 in spite of strict control measures. For transportation, despite strict emission standards, its contribution increases remarkably due to the rapid growth of vehicle population. When both ambient and household PM2.5 exposures are taken into account, the mortality due to integrated population-weighted exposure to PM2.5 (IPWE) drops from 1.78 (1.46-2.09) million in 2005 to 1.28 (1.05-1.52) million in 2015. Most of the IPWE reduction comes from domestic combustion as a result of urbanization and improved income, whereas this sector remains the largest contributor (58%) to IPWE-related health risk in 2015. Our results suggest that the government should dynamically adjust the air pollution control strategy according to the change in source contributions. Domestic combustion and agriculture should be prioritized considering their predominant contributions to mortality and the lack of effective control policies. More stringent control measures for industry and transportation are necessary since the existing policies have not adequately reduced their health impacts. Electricity production is no longer the top priority of air pollution control policies given its lower health impact compared with that of other sources.

16.
Am J Physiol Cell Physiol ; 317(5): C932-C941, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411920

RESUMO

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.

17.
Int J Biol Macromol ; 140: 288-293, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31400419

RESUMO

In this study, three sulfated polysaccharides (S-RSP1-2, S-RSP1-4 and S-RSP1-8) from Rhodiola sachalinensis were produced by chlorosulfonic acid-pyridine method. d-gal was used to develop an oxidative stress model in the mouse embryonic fibroblast cell line NIH 3T3. Effects of the three sulfated polysaccharides on d-gal-induced oxidative stress were investigated. The results showed that S-RSP1-4 improved the viability of the d-gal-induced oxidative stress in NIH 3T3 cells. The sulfated polysaccharides were found to have a better protective effect against d-gal-induced oxidative stress as compared to the native polysaccharide. Scanning electronmicroscopy also showed a significant change in the surface morphology of sulfated polysaccharides. In addition, the sulfated polysaccharides had noticeable DPPH radical-scavenging activity. In summary, our results demonstrated that d-gal was able to induce oxidative stress in NIH 3T3 cells, and sulfated group might play an important role in resistance to d-gal-induced oxidative damage.

18.
World J Pediatr ; 15(5): 454-464, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372844

RESUMO

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inheritance and a different prognosis, characterized by macrocephaly, delayed motor and cognitive development, and bilateral abnormal signals in cerebral white matter (WM) with or without cysts on magnetic resonance imaging (MRI). This study aimed to reveal the clinical and genetic features of MLC patients with GLIALCAM mutations and to explore the brain pathological characteristics and prognosis of mouse models with different modes of inheritance. METHODS: Clinical information and peripheral venous blood were collected from six families. Genetic analysis was performed by Sanger sequencing of GLIALCAM. GlialcamArg92Trp/+ and GlialcamLys68Met/Thr132Asn mouse models were generated based on mutations from patients (c.274C>T(p.Arg92Trp) (c.203A>T(p.Lys68Met), and c.395C>A (p.Thr132Asn))). Brain pathologies of the mouse models at different time points were analyzed. RESULTS: Six patients were clinically diagnosed with MLC. Of the six patients, five (Pt1-Pt5) presented with a heterozygous mutation in GLIALCAM (c.274C>T(p.Arg92Trp) or c.275G>C(p.Arg92Pro)) and were diagnosed with MLC2B; the remaining patient (Pt6) with two compound heterozygous mutations in GLIALCAM (c.203A>T (p.Lys68Met) and c.395C>A (p.Thr132Asn)) was diagnosed with MLC2A. The mutation c.275C>G (p.Arg92Pro) has not been reported before. Clinical manifestations of the patient with MLC2A (Pt6) progressed with regression, whereas the course of the five MLC2B patients remained stable or improved. The GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mouse models showed vacuolization in the anterior commissural WM at 1 month of age and vacuolization in the cerebellar WM at 3 and 6 months, respectively. At 9 months, the vacuolization of the GlialcamLys68Met/ Thr132Asn mouse model was heavier than that of the GlialcamArg92Trp/+ mouse model. Decreased expression of Glialcam in GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mice may contribute to the vacuolization. CONCLUSIONS: Clinical and genetic characterization of patients with MLC and GLIALCAM mutations revealed a novel mutation, expanding the spectrum of GLIALCAM mutations. The first Glialcam mouse model with autosomal recessive inheritance and a new Glialcam mouse model with autosomal dominant inheritance were generated. The two mouse models with different modes of inheritance showed different degrees of brain pathological features, which were consistent with the patients' phenotype and further confirmed the pathogenicity of the corresponding mutations.

19.
World J Gastroenterol ; 25(30): 4222-4234, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435175

RESUMO

BACKGROUND: Liver fibrosis is a refractory disease whose persistence can eventually induce cirrhosis or even liver cancer. Early liver fibrosis is reversible by intervention. As a member of the transforming growth factor-beta (TGF-ß) superfamily, bone morphogenetic protein 7 (BMP7) has anti-liver fibrosis functions. However, little is known about BMP7 expression changes and its potential regulatory mechanism as well as the relationship between BMP7 and TGF-ß during liver fibrosis. In addition, the mechanism underlying the anti-liver fibrosis function of BMP7 needs to be further explored. AIM: To investigate changes in the dynamic expression of BMP7 during liver fibrosis, interactions between BMP7 and TGF-ß1, and possible mechanisms underlying the anti-liver fibrosis function of BMP7. METHODS: Changes in BMP7 expression during liver fibrosis and the interaction between BMP7 and TGF-ß1 in mice were observed. Exogenous BMP7 was used to treat mouse primary hepatic stellate cells (HSCs) to observe its effect on activation, migration, and proliferation of HSCs and explore the possible mechanism underlying the anti-liver fibrosis function of BMP7. Mice with liver fibrosis received exogenous BMP7 intervention to observe improvement of liver fibrosis by using Masson's trichrome staining and detecting the expression of the HSC activation indicator alpha-smooth muscle actin (α-SMA) and the collagen formation associated protein type I collagen (Col I). Changes in the dynamic expression of BMP7 during liver fibrosis in the human body were further observed. RESULTS: In the process of liver fibrosis induced by carbon tetrachloride (CCl4) in mice, BMP7 protein expression first increased, followed by a decrease; there was a similar trend in the human body. This process was accompanied by a sustained increase in TGF-ß1 protein expression. In vitro experiment results showed that TGF-ß1 inhibited BMP7 expression in a time- and dose-dependent manner. In contrast, high doses of exogenous BMP7 inhibited TGF-ß1-induced activation, migration, and proliferation of HSCs; this inhibitory effect was associated with upregulation of pSmad1/5/8 and downregulation of phosphorylation of Smad3 and p38 by BMP7. In vivo experiment results showed that exogenous BMP7 improved liver fibrosis in mice. CONCLUSION: During liver fibrosis, BMP7 protein expression first increases and then decreases. This changing trend is associated with inhibition of BMP7 expression by sustained upregulation of TGF-ß1 in a time- and dose-dependent manner. Exogenous BMP7 could selectively regulate TGF-ß/Smad pathway-associated factors to inhibit activation, migration, and proliferation of HSCs and exert anti-liver fibrosis functions. Exogenous BMP7 has the potential to be used as an anti-liver fibrosis drug.

20.
Environ Sci Technol ; 53(18): 11013-11022, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31415163

RESUMO

Mass adoption of electric vehicles (EVs) is widely viewed as essential to address climate change and requires a compelling case for ownership worldwide. While the manufacturing costs and technical capabilities of EVs are similar across regions, customer needs and economic contexts vary widely. Assessments of the all-electric-range required to cover day-to-day driving demand, and the climate and economic benefits of EVs, need to account for differences in regional characteristics and individual travel patterns. To meet this need travel profiles for 1681 light-duty passenger vehicles in China, the U.S., and Germany were used to make the first consistent multiregional comparison of customer and greenhouse gas (GHG) emission benefits of EVs. We show that despite differences in fuel prices, driving patterns, and subsidies, the economic benefits/challenges of EVs are generally similar across regions. Individuals who are economically most likely to adopt EVs have GHG benefits that are substantially greater than for average drivers. Such "priority" EV customers have large (32%-63%) reductions in cradle-to-grave GHG emissions. It is shown that low battery costs (below approximately $100/kWh) and a portfolio of EV offerings are required for mass adoption of electric vehicles.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA