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1.
Seizure ; 79: 20-26, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32416565

RESUMO

PURPOSE: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis. METHODS: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs. RESULTS: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up. CONCLUSIONS: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy.

2.
Pflugers Arch ; 472(1): 117-133, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875236

RESUMO

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1-/-). Then, we characterized the survival rate and behavioral phenotype of CPLX1-/- rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1-/- rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1-/- rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1-/- rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1-/- rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1.

3.
J Mol Neurosci ; 70(3): 308-319, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845102

RESUMO

Tree shrews, possessing higher developed motor function than rats, were more suitable to study neurological behavior after spinal cord injury (SCI). Here, we established a feasible behavioral assessment method to detect the degree of ethology recovery in tree shrew subjected to spinal cord transection (SCT). Tree shrews were divided into normal group, sham group, and SCT group. The tree shrew in sham group was subjected to laminectomy without SCI, while the tree shrews in the SCT group were subjected to a complete SCT in thoracic 10 (T10). A novel neurobehavior assessment scale was established, in which, the behavior index including slow advancement, fast advancement, standing, shaking head, voluntary jump, lateral movement, and tail status, was determined, respectively. Meanwhile, magnetic resonance imaging (MRI) was applied to observe the structure of the spinal cord, and diffusion tensor imaging (DTI)-based white matter mapping was used to show the fibers of the spinal cord. As a result, a marked decrease in locomotor function and consciousness was seen in tree shrews with SCT, and the detection of MRI showed the collapsing of nerve fibers after SCT is completely cut and there is corresponding to the behavior change. Together, the present study provided a novel and feasible method that can be used to assess the neurobehavior in SCT model from tree shrews, which may be useful to the SCI translational study in future preclinic trial.

4.
Sci Rep ; 9(1): 18018, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784655

RESUMO

Scientific management of nitrogen (N) fertilizer has a significant effect on yield while also reducing the environmental risks. In this study, we conducted field experiments over three years at two different sites (Zhengzhou and Shangshui) in Henan Province, China, using different N application rates (0, 90,180, 270, and 360 kg ha-1) to determine the relationships between soil N supply and N demand in winter wheat (Triticum aestivum L.). Optimal N input was then determined. Both sites showed the same trend. Namely, aboveground N uptake and soil nitrate N (NO3--N) increased with increasing N, while NO3--N decreased with increasing soil depth, gradually moving downwards with growth. A significant correlation (p < 0.001) between increasing aboveground N uptake and increasing NO3--N was also observed under N application, with the best relationships occurring in the 20-60 cm layer during jointing-anthesis (R2 = 0.402-0.431) and the 20-80 cm layer at maturity (R2 = 0.474). Root weight density showed the same spatial-temporal characteristics as NO3--N, following a unimodal trend with increasing N, and peaking at 90 kg ha-1. The root weight density was mainly distributed in the 0-60 cm layer (above 80%), with the 20-60 cm layer accounting for 30% of the total root system. In this layer, the root weight density was also significantly positively correlated with aboveground N uptake. Wheat yield reached saturation under high N (>270 kg ha-1), with a sharp decrease in N use efficiency (NUE) and linear increase in residual NO3--N. To balance yield and the risk of environmental pollution in the experimental area, an N application rate of 180-270 kg ha-1 is recommended under sufficient irrigation, thereby supporting a well-developed root system while ensuring balance between N supply and demand.

5.
Math Biosci Eng ; 16(6): 7510-7525, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31698626

RESUMO

Impressed current cathodic protection (ICCP) was widely applied for the corrosion control of reinforced concrete. During the ICCP treatment, the anodic reactions happened on the primary anode surface may induce acidification and subsequently pH drop in the vicinity of the anode, leading to damage of the external anode mortar. In this study, the relationship between the applied current (simulating ICCP treatment) on the Ti mesh anode and pH alterations in simulated concrete pore (SCP) solution (with/without chlorides) was investigated. It was found that the applied current slightly reduced the corrosion resistance of Ti mesh; this negative effect was more pronounced in the presence of chlorides. The pH value of SCP solution near Ti mesh anode decreased when the external current was applied. The consumption rate of OH- ion was higher in the chloride-containing SCP solution. A mathematical model was proposed between the electric charge quantity (Q) and OH- concentration (cOH-) in SCP solution near Ti mesh anode. This model is a useful tool to quantitatively identify the acidification damage induced by impressed current from the perspective of pH alternation near Ti mesh anode.

6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 478-482, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642222

RESUMO

OBJECTIVE: To determine the potential value of the two-dimensional (2D) cardiac magnetic resonance imaging (CMR) tissue tracking (CMR-TT) method in assessing the cardiac function of tree shrew at 7T. METHODS: Healthy adult tree shrews (male, n=8) and spraguedawley rats(male, n=8) were selected for this study. CMR was performed to acquire the short-axis images of left ventricle at 7T using the same appropriative coil and cine sequence for all experimental animals. The CMR images were processed using the professional cardiac analysis software, calculating ejection fraction (EF), radial peak sysolic strain (Err), circumferential peak sysolic strain (Ecc), radial peak sysolic displacement (DR), and LVM/BM 〔the ratio of left ventricular mass (LVM) to body mass (BM)〕. RESULTS: Cine imaging for the tree shrews was 100% successful following the CMR protocol for the rats, with clearly visible main segments of cardiac. Significant differences in EF, Err, Ecc and DR were found between the two groups of animals (P < 0.01). The tree shrews has lower EF, Err and Ecc than the rats. Err and Ecc appeared in the fifteenth phase in left ventriclar systole in the tree shrews, compared with the tenth phase in the rats.The tree shrews also had higher LVM/BM than the rats. CONCLUSION: The cardiac function of tree shrew can be assessed using the 2D CMR-TT method despite significant differences across species.


Assuntos
Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Tupaiidae , Função Ventricular Esquerda , Animais , Imagem por Ressonância Magnética , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Volume Sistólico , Sístole
7.
JMIR Mhealth Uhealth ; 7(9): e11229, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31516128

RESUMO

BACKGROUND: The diagnosis of paroxysmal events in infants is often challenging. Reasons include the child's inability to express discomfort and the inability to record video electroencephalography at home. The prevalence of mobile phones, which can record videos, may be beneficial to these patients. In China, this advantage may be even more significant given the vast population and the uneven distribution of medical resources. OBJECTIVE: The aim of this study is to investigate the value of mobile phone videos in increasing the diagnostic accuracy and cost savings of paroxysmal events in infants. METHODS: Clinical data, including descriptions and home videos of episodes, from 12 patients with paroxysmal events were collected. The investigation was conducted in six centers during pediatric academic conferences. All 452 practitioners present were asked to make their diagnoses by just the descriptions of the events, and then remake their diagnoses after watching the corresponding home videos of the episodes. The doctor's information, including educational background, profession, working years, and working hospital level, was also recorded. The cost savings from accurate diagnoses were measured on the basis of using online consultation, which can also be done easily by mobile phone. All data were recorded in the form of questionnaires designed for this study. RESULTS: We collected 452 questionnaires, 301 of which met the criteria (66.6%) and were analyzed. The mean correct diagnoses with and without videos was 8.4 (SD 1.7) of 12 and 7.5 (SD 1.7) of 12, respectively. For epileptic seizures, mobile phone videos increased the mean accurate diagnoses by 3.9%; for nonepileptic events, it was 11.5% and both were statistically different (P=.006 for epileptic events; P<.001 for nonepileptic events). Pediatric neurologists with longer working years had higher diagnostic accuracy; whereas, their working hospital level and educational background made no difference. For patients with paroxysmal events, at least US $673.90 per capita and US $128 million nationwide could be saved annually, which is 12.02% of the total cost for correct diagnosis. CONCLUSIONS: Home videos made on mobile phones are a cost-effective tool for the diagnosis of paroxysmal events in infants. They can facilitate the diagnosis of paroxysmal events in infants and thereby save costs. The best choice for infants with paroxysmal events on their initial visit is to record their events first and then show the video to a neurologist with longer working years through online consultation.

8.
Genet Test Mol Biomarkers ; 23(8): 533-556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31373850

RESUMO

Background: To determine whether vitamin D receptor (VDR) gene polymorphisms are correlated with susceptibility to diabetic vascular complications. Methods: We included all eligible studies, and used Stata12.0 to calculate the pooled results. Results: Eight thousand eleven diabetic patients and 1635 normal controls from 27 studies were included. Our results showed that there was no correlation between VDR gene TaqI variants and diabetic nephropathy (DN) or diabetic retinopathy (DR) susceptibility. In comparison with diabetic patients without DN, there was a link between the VDR gene ApaI variant and DN susceptibility under allelic model (p = 0.029) in all populations. In addition, the VDR gene BsmI variant correlated with DN under both dominant (p = 0.005) and allelic (p = 0.003) models in Asian populations. The VDR gene FokI variant was also correlated with DN susceptibility under the recessive model (p = 0.027) in the Asian subgroup. In comparison with diabetic patients without DR, we identified a link between the VDR gene ApaI variant and DR susceptibility under the dominant model (p = 0.034) in all populations. Also, the VDR gene FokI variant was correlated with DR under the recessive (p = 0.016), the allelic (p = 0.001), and the dominant (p < 0.001) models in all populations. When compared with healthy controls, the VDR gene BsmI variant was associated with DR under the additive (p = 0.014), the allelic (p = 0.033), and the dominant (p < 0.001) models in Indian populations. Conclusions: The VDR gene BsmI, ApaI, and FokI gene variants are associated with DN and DR susceptibility. No association was found between the VDR gene TaqI gene variants and diabetic vascular complications.


Assuntos
Diabetes Mellitus/genética , Angiopatias Diabéticas/genética , Predisposição Genética para Doença , Polimorfismo Genético , Receptores de Calcitriol/genética , Grupos de Populações Continentais/genética , Nefropatias Diabéticas/genética , Humanos
9.
Chin Med J (Engl) ; 132(15): 1796-1801, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31343434

RESUMO

BACKGROUND: Recent genome-wide association studies have identified an important role of T-cell receptor α (TRA) gene in the development of narcolepsy type 1. However, the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear. This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy. METHODS: Totally, 903 patients with narcolepsy type 1 were included in the study. Patients were divided into different groups according to their symptoms. First, 13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy. We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy. Further, we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model. RESULTS: According to the results of the logistic regression, TRA haplotypes TG and CT were significantly associated with auditory hallucination, with odds ratios of 1.235 (95% confidence interval [CI], 1.012-1.507) and 1.236 (95% CI, 1.012-1.511), respectively (P < 0.05). CONCLUSIONS: The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1. However, further studies are needed to confirm our results and explore the underlying mechanisms.


Assuntos
Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T/genética , Narcolepsia/genética , Adolescente , Criança , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
10.
Brain Res ; 1718: 194-200, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077648

RESUMO

BACKGROUND: Tree shrew, as a kind of small and inexpensive animal between insectivores and primates with the general anatomy being similar to human, could be considered as developed animal model for brain ischemia (BI) study. However, there is no neural behavior scores criterion from tree shrew with BI up to now. METHODS: To produce BI model of tree shrew, a novel systematic neurobehavioral assessment scale, named as neural behavior scores (NBS) including aggressive behavior, seeking behavior, gait, startle reflex, high jump and warped-tail phenomenon was firstly established and used in this study. Moreover, magnetic resonance imaging (MRI) was performed on the first day after the operation to detect the imaging changes caused by ischemia. Then TTC, HE staining and immunofluorescent staining for GFAP and NeuN, were performed 24 h after surgery respectively. RESULTS: NBS in BI group were significantly higher than that of sham operation group at 1d, 3d, 5d and 7d after ischemia. Meanwhile, compared with the sham operation group, the T2 images demonstrated significant higher signal and local brain swelling after cerebral ischemia in tree shrews. The staining of TTC and HE showed apparent infarction and necrosis of the cerebral region, and most of neurons exhibited a shrink. CONCLUSION: We have successfully established the BI model of tree shrew, confirmed by NBS (a new developed method), MRI, HE staining, TTC staining and immunofluorescence staining. It is the first time to report a novel neurobehavioral assessment scale for BI in tree shrew.

11.
Brain Res ; 1719: 77-88, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31082354

RESUMO

Neonatal hypoxic-ischemic encephalopathy (HIE) always results in severe neurologic dysfunction, nevertheless effective treatments are limited and the underlying mechanism also remains unclear. In this study, we firstly established the neonatal HIE model in the postnatal day 7 SD rats, Zea-Longa score and TTC staining were employed to assess the neurological behavior and infarct volume of the brain after cerebral hypoxia-ischemia (HI). Afterwards, protein chip was adopted to detect the differential proteins in the right cortex, hippocampus and lung, ultimately, PDGF was noticed. Then, immunohistochemistry, immunofluorescence double staining of NeuN/PDGF, and western blot were used to validate the expression level of PDGF in the cortex and hippocampus at 6 hours (h), 12 h and 24 h after HI. To determine the role of PDGF, the primary cortical neurons were prepared and performed PDGF shRNA administration. The results showed that HIE induced a severe behavioral dysfunction and brain infarction in neonatal rats, and the expression of PDGF in right cortex and hippocampus was remarkably increased after HI. Whereas, suppressing PDGF resulted in a significant loss of neurons and inhibition of neurite growth. Moreover, the protein level of P-PI3K and P-AKT signaling pathways were largely decreased following PDGF-shRNA application in the cortical neurons. In conclusion, PDGF suppression aggravated neuronal dysfunction, and the underlying mechanism is associated with inhibiting the phosphorylation of P-PI3K and P-AKT. Together, PDGF regulating PI3K and AKT may be an important panel in HIE events and therefore may provide possible strategy for the treatment of HIE in future clinic trail.

12.
ACS Appl Mater Interfaces ; 11(16): 14830-14839, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30945528

RESUMO

High-Ni layered oxides are potential cathodes for high energy Li-ion batteries due to their large specific capacity advantage. However, the fast capacity fade by undesirable structural degradation in liquid electrolyte during long-term cycling is a stumbling block for the commercial application of high-Ni oxides. In this work, a functional gel polymer electrolyte, grafted with sodium alginate, is introduced to increase the stability of high-Ni oxide cathodes at the levels of both the particle and electrode. An in situ generated ion-conducting layer appears on the interface through the chemical interaction between transition-metal cations of the cathode and the metalophilic reticulum group in sodium alginate. Such a tailoring layer can not only enhance the interfacial compatibility on the cathode/electrolyte interface, reducing the interfacial resistance, but also inhibit the HF corrosion, suppressing the dissolution of transition-metal cations and harmful gradient distribution of components through the oxide cathode at the electrode level. Meanwhile, detrimental microcracks in oxide microspheres and between primary crystallites are impressively inhibited at the particle level. The high-Ni oxide cathode with the metalophilic gel polymer electrolyte shows excellent cycle stability with large initial capacity of 204.9 mA h g-1 at a 1.0 C rate and high discharge capacity retention within 300 cycles at high temperature.

13.
Biomed Res Int ; 2019: 6821219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915356

RESUMO

Background: Glioma is the most common malignant brain tumor and the patients are prone to poor prognosis. Due to limited treatments, new drug exploration has become a general trend. Therefore, the objective of this study is to investigate the effect of the new drugs C18H17NO6 and its combination with Scutellarin on glioma cells and the underlying mechanism. Method: U251 and LN229 cells were administrated with C18H17NO6 and its combination with Scutellarin. The proliferation ability of glioma cells was determined by cell counting kit-8, plate clone formation assay, and EdU incorporation assay. The cell cycle and apoptosis detection were detected by flow cytometry. Moreover, TUNEL assay was also used for cell apoptosis analysis. Then, the transfer ability of cells was achieved through wound healing assay. Furthermore, polymerase chain reaction (PCR) test and western bolt analysis were used to detect the mRNA expression and protein expression, respectively. Lastly, immunofluorescence was for the purity identification of astrocyte. Result: The results showed that, with the increasing dose of C18H17NO6, the cell inhibition rate, the cells in G1 phase, and the apoptosis rate were gradually increased, but the clone number, proliferation rate, and the cells in G2 and S phases were gradually decreased in comparison with control group. However, with the increase of C18H17NO6, the transferred rate of U251 and LN229 was not significantly augmented, expect that on U251 in C18H17NO6 5 µM group. In addition, Scutellarin 200 µM has little effect on proliferation, with the inhibition rate 10-20% and proliferation rate except U251 in Scutellarin 200 µM group similar to that in control group. Moreover, compared to control group, Scutellarin 300 µM increased the U251 cells in G2 and S phases and the apoptosis rate of LN229 but decreased the LN229 cells in G2 and S phases. Besides, in Scutellarin 200 µM group, the transfer ability of LN229 was inhibited, but not in U251. Furthermore, if C18H17NO6 was combined with Scutellarin 200/300µM, the proliferation and transferred ability were suppressed and the apoptosis was elevated in LN229 cell in comparison with C18H17NO6 alone. Dramatically, the combined effect on U251 was the exact opposite. Importantly, there was little toxicity on astrocyte under the dose of C18H17NO6 and Scutellarin in the study. In molecular level, the mRNA and protein expression of Fas-associated factor 1 (FAF1) expression in U251 and LN229 were upregulated by C18H17NO6 and its combination with Scutellarin, especially the protein expression. Conclusion: C18H17NO6 could efficiently suppress cell proliferation and induce cell apoptosis in glioma cells, and its combination with Scutellarin had a promoting effect, in which the underlying mechanism referred to the upregulation of Fas-associated factor 1.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma , Glucuronatos/farmacologia , Proteínas de Neoplasias/biossíntese , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Humanos
14.
Ther Apher Dial ; 23(5): 425-436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30701705

RESUMO

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73-0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66-0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55-0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00-2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72-1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68-1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86-2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70-1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.


Assuntos
Predisposição Genética para Doença , Nefrolitíase/genética , Receptores de Calcitriol/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nefrolitíase/etnologia , Polimorfismo Genético , Adulto Jovem
15.
Cell Mol Neurobiol ; 39(3): 451-460, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30778712

RESUMO

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.


Assuntos
Ligante 4-1BB/metabolismo , Isquemia Encefálica/metabolismo , Ligante 4-1BB/sangue , Animais , Linfócitos B/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Membrana Celular/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
BMC Neurol ; 19(1): 30, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791893

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a complication that occurs during various diseases' treatment. Imaging examination is the gold standard for diagnosis. PRES frequently occurrence in patients with hematological malignancies results in poorer prognosis and higher mortality. We aim to establish a practical and operable scale for early prediction, assessment of the severity of the Posterior Reversible Encephalopathy Syndrome, and timely intervention for better prognosis. METHODS: The scale designed by reviewing the literature and by referring to clinical practice. We assessed the reliability and validity of the scale. Scale-based assessment of children undergoing chemotherapy for acute lymphoblastic leukemia conducted as early warning and intervention for those who may have PRES. RESULTS: Establishment of Posterior Reversible Encephalopathy Syndrome early warning scoring (PEWS) scale included three parts, as follows: (1) risk factors, including underlying disease, hypertension, Infection, and drug toxicity; (2) clinical features, including high cranial pressure, visual symptoms, seizure, and disturbance of consciousness; and (3) EEG features, including slow wave and epileptiform discharges. Utility assessment of PEWS scale showed that in 57 patients with acute lymphoblastic leukemia, 54 scored less than 10 and none of them detected as PRES. The other two had scores of 12 and 13 both diagnosed with PRES by brain MRI scan. CONCLUSIONS: PEWS scale can predict PRES early. PRES was highly suspected when the score was 10 points and more. Thus, prophylactic intervention can give to improve the prognosis of PRES.


Assuntos
Diagnóstico Precoce , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Adolescente , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Fatores de Risco
17.
Cytokine ; 115: 8-12, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30616035

RESUMO

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.

18.
Huan Jing Ke Xue ; 40(1): 437-444, 2019 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628303

RESUMO

Surface farmland soil samples were collected from 135 different sites in a 64 km2 area around a lead and zinc smelter in Jiaozuo City, China. The concentration of the selected heavy metals (Cu, Zn, Pb, Cr, Cd, Ni, V, and Co) was analyzed and the spatial distribution of these heavy metals in the farmland was determined using the kriging interpolation technique (ArcGis 10.1). The enrichment factor, potential ecological risk model, and potential health risk model were used to assess the contamination level and potential risk of heavy metals in farmland surface soil. The results show that the average contents of Cd, Pb, Cr, and Zn in farmland soil are higher than the background content of these metals in the Henan Province and the average content of Cd is 2.8 times higher than that of class Ⅱ of the environmental quality standard for soils in China (GB 15618-1995). The heavy metal contamination in the west of the study area is higher than that in the east and the soil around the lead and zinc smelter (within 3 km) is severely contaminated with Pb and Cd, which is consistent with the location of the industries causing the pollution. The enrichment factors show that the soil is severely contaminated with Cd; partial sampling points are seriously contaminated with Pb, Cu, and Zn; the Cr and Co pollution is small; and Ni and V are almost not affected by human activities. The results of the risk assessment indicate that Cd poses serious ecological and health risks, Pb and Cu pose serious ecological risks, and Cr poses a serious cancer risk.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Poluentes do Solo/análise , Zinco , China , Cidades , Fazendas , Humanos , Metalurgia , Medição de Risco , Solo/química , Análise Espacial
19.
World J Gastroenterol ; 25(2): 233-244, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30670912

RESUMO

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM: To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS: Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS: In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION: After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/genética , Redes Reguladoras de Genes/genética , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Biomarcadores Tumorais/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas/estatística & dados numéricos , Conjuntos de Dados como Assunto , Progressão da Doença , Neoplasias Esofágicas/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Software , Transcriptoma/genética
20.
J Pineal Res ; 66(1): e12532, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30320949

RESUMO

Paraquat (PQ), a broad-spectrum agricultural pesticide, causes cellular toxicity by increasing oxidative stress levels in various biological systems, including the reproductive system. PQ exposure causes embryotoxicity and reduces the developmental abilities of embryos. However, there is little information regarding the toxic effects of PQ on oocyte maturation. In this study, we studied the toxic effects of PQ exposure and the effects of melatonin on PQ-induced damage in bovine oocytes. PQ exposure disrupted nuclear and cytoplasmic maturation, which was manifested as decreased cumulus cell expansion, reduced first polar body extrusion, and abnormal distribution patterns of cortical granules and mitochondria. In addition, PQ treatment severely disrupted the ability of the resulted in vitro-produced embryos to develop to the blastocyst stage. Moreover, PQ exposure significantly increased the intracellular reactive oxygen species (ROS) level and early apoptotic rate, and decreased the glutathione (GSH) level, antioxidative CAT and GPx4 mRNA, and apoptotic-related Bcl-2/Bax mRNA ratio. These results indicated that PQ causes reproductive toxicity in bovine oocytes. Melatonin application resulted in significant protection against the toxic effects of PQ in PQ-exposed oocytes. The mechanisms underlying the role of melatonin included the inhibition of PQ-induced p38 mitogen-activated protein kinase (MAPK) activation, and restoration of abnormal trimethyl-histone H3 lysine 4 (H3K4me3) and trimethyl-histone H3 lysine 9 (H3K9me3) levels. These results reveal that melatonin serves as a powerful agent against experimental PQ-induced toxicity during bovine oocyte maturation and could form a basis for further studies to develop therapeutic strategies against PQ poisoning.


Assuntos
Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Paraquat/toxicidade , Animais , Antioxidantes/metabolismo , Bovinos , Feminino , Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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