RESUMO
BACKGROUND@#Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism.@*METHODS@#Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo . The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay.@*RESULTS@#In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N 6 -methyladenosine (m 6 A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m 6 A site on the 3'-untransated regions (3'-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells.@*CONCLUSION@#HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
Assuntos
Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Hipóxia , MicroRNAs/genética , RNA , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores Depuradores Classe B/metabolismo , Neoplasias Gástricas/genéticaRESUMO
Objective To investigate the effect of donepezil hydrochloride on the expression of Calpain Ⅰ-Cdk5/p25 pathway in the hippocampal CA1 area by cerebral ischemia and reperfusion in mice.Methods Mice were divided into model group,sham-operated group and donepezil-treated group.The expression of Calpain Ⅰ in hippocampal CA1 area was measured by immunohistochemistry staining respectively at 4,6 and 8 weeks post cerebral ischemia and reperfusion.Western blot was used to evaluate Cdk5 and p25 protein expression.Results The abilities of learning and memory performance was damaged significantly at 4,6 and 8 weeks after surgery compared to sham-operated group (P＜ 0.05).The expression of Calpain Ⅰ of model group were (0.098 ± 0.009),(0.129 ±0.01),(0.116 ± 0.01),which were higher than that of sham-operated group (0.03 ± 0.003),(0.031 ± 0.003),(0.029 ±0.003) and there was significant difference (P ＜ 0.05).The expression of Cdk5 in model group was (0.54 ± 0.05),(0.73 ± 0.07),(0.7 ± 0.06),which were higher than that of sham-operated group (0.23 ±0.02),(0.31 ± 0.02),(0.33 ± 0.02) and there was significant difference (P ＜ 0.05).The expression of p25 in model group was (0.44 ± 0.04),(0.51 ± 0.04),(0.55 ± 0.06),which were higher than that of sham-operated group(0.19 ± 0.02),(0.24 ± 0.02),(0.2 ± 0.02) and there was significant difference (P ＜ 0.05).The expression of Calpain Ⅰ of donepezil-treated group was (0.041 ± 0.004),(0.054 ± 0.004),(0.046 ± 0.003),which were lower than that of model group.The expression of Cdk5 was (0.28 ± 0.02),(0.33 ± 0.03),(0.38 ± 0.02),and expression of p25 was (0.26 ± 0.02),(0.25 ± 0.03),(0.21 ± 0.02),which were lower than that of model group respectively(P ＜ 0.05).Conclusion Donepezil hydrochloride probably improve the learning and memory abilities by reducing the expression of Calpain Ⅰ and Cdk5/p25.
RESUMO
Objective To investigate the pattern of the cerebral white matter lesions in patients with mild and moderate Alzheimer's disease(AD)and healthy controls using proton magnetic resonance spectroscopy(~1H-MRS)and diffusion tensor imaging(DTI).Methods Twenty AD patients and Twenty healthy controls were recrnited.All subjects underwent clinical examination,neuropsychological assessment.The quantitative analysis of N-acetylaspartate(NAA),myoinositol(mI),Chotine(Cho)and Creatine(Cr)resonance signals in region of interests(ROIs)located in the paraventricular white matter region bilaterally were measured.Ratios of NAA/Cr,mI/Cr and Cho/Cr were calculated in two groups.In addition,conventional MRI and DTI scanning were received,fractional anisotropy(FA)and mean diffusivity(MD)values of white matter in the same regions were measured respectively.Results No significant difference between two groups were observed in NAA/Cr ratio(P＞0.05).A significantly increased mI/Cr and Cho/Cr were found in AD patients than in controls(P＜0.05).FA and MD values in AD patients were 0.470±0.082 and 0.771±0.099,and in controls were 0.539±0.068 and 0.691±0.064,respectively.FA value decreased significantly in AD patients(P＜0.05),M D value increased significantly in AD patients(P＜0.05).After controlling for age-related,partial correlation analysis revealed a negtive correlation between mI/Cr and FA value in the patients with AD(P＜0.05).No correlation between mI/Cr and MD was found(P＞0.05).Conclusion The results suggest that not only the gray matter is injured,but also the white matter is abnormal in AD patients.Combining ~1H-MRS with DTI alterations could provide the valuable informations about white matter lesions in AD patients.
RESUMO
Objective To investigate the relationship of lacunar infarction (LI) and white matter lesion with cognitive impairment in patients with subcortical ischemic vascular disease (SIVD) Methods Fifty-three patients were diagnosed as SIVD according to the criteria of Erkinjuntti. The symptoms and signs were recorded by an interview and examination, and neuropsychological assessment and magnetic resonance imaging (MRI) were performed. A semi-automated MRI quantitative method was used to measure the volume of white matter hyperintensity (WMH) and the number of LI was counted. Correlation and the partial correlation analysis were performed to examine the relationship of general cognitive function with the volume of WMH and the number of LI. Results The pseudobulbar paralysis symptom and the upper motoneuron injury sign were the most common in these patients (18.9% and 37.7%). Correlation analysis showed that there was positive correlation between the volume of WMH and age (r = 0. 518, P < 0. 05), and there was negative correlcction between mini-metal state examination (MMSE) scures and the volume of WMH (r=-0.514, P<0. 05), After controlling confounding factors, only age was positively correlated with the volume of WMH (r=0. 400, P=0. 004). There were negative correlation between the number of LI, the volume of WMH and MMSE scores(r=-0. 456,-0. 514,-0. 385,-0. 382;all P<0. 05), and the years of education was positively correlated with MMSE scores (r= 0. 518, P< 0. 001). Conclusions Age may not be the main risk factor for cognitive impairment in patients with SIVD. The volume of WMH and the number of LI are independent risk factors for cognitive impairment in patients with SIVD. Patients with severer SIVD or more LI show poorer performance on cognitive function.
RESUMO
Objective: To observe the clinical efficacy of combined needle-embedding and SSRIs for depressive sleep disorder. Method: Upon admission, 71 depression cases were randomized into needle-embedding group of 24 cases, using combined needle-embedding and SSRIs, acupuncture group of 21 cases, using combined acupuncture and SSRIs, and medication group of 26 cases, using SSRIs alone. After 1, 2, 4 and 6 weeks of treatment, the HAMD sleep scores were compared. Result: The HAMD sleep scores in the needle-embedding and acupuncture group were remarkably superior to the medication group and there was significant statistical difference after 1, 2 and 4 weeks of treatment (P<0.01). However, there was no statistical difference after 6 weeks of treatment. Conclusion: SSRIs can improve HAMD sleep scores. The combined needle-embedding or acupuncture with SSRIs can work faster and better than medication alone. There was no statistical difference between needle-embedding and acupuncture group, however, needle-embedding can reduce the treatment frequencies and therefore has more active clinical meaning.
RESUMO
Objective To analyse the role of AEEG and MRI in diagnosis of epilepsy on its primary epileptic focus and pathologic lesions. Methods We reviewed the results of sixty epileptic patients on routine EEG, twenty-four hour active EEG(AEEG),CT scanning and MRI examinations. The relationship between epileptic discharges of AEEG and lesions of MRI was analyzed by using ? 2 test. Results AEEG showed a higher sensitivity in finding epileptic focus in 80% patients, as compared with the rate of 32% in routine EEG. The sensitivity on finding the cerebral lesion related to the epileptic focus by using MRI was 60%, as compared with the rate of 33% in CT scanning. There was a correlative relationship between the AEEG discharge foci and the lesions found by MRI( P