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Objective To study the clinical effect of levosimendan combined with recombinant human brain natriuretic peptide(rhBNP)on patients with acute heart failure.Methods A total of 100 patients with acute heart failure in the hospital from December 2019 to December 2021 were selected as the research sub-jects.According to different treatment options,the subjects were divided into the control group,levosimendan group,rhBNP group and combined treatment group,with 25 cases in each group.The control group received traditional conventional diuretic,tube expansion and other treatment;the levosimendan group was treated with levosimendan on the basis of the control group;the rhBNP group was treated with rhBNP on the basis of the control group;the combined treatment group was treated with levosimendan and rhBNP on the basis of the control group.The improvement of New York Heart Association(NYHA)classification,death,rehospitaliza-tion rate,6-minute walking distance,improvement of serological indicators and adverse reactions were recor-ded in each group.Results Before treatment,there was no significant difference in baseline data between the groups(P>0.05).On the 1 st and 3 rd day after treatment,the improvement of NYHA classification in the combined treatment group was better than that in the other groups(P<0.05),and the improvement of NY-HA classification in the levosimendan group and rhBNP group was better than that in the control group(P<0.05).The readmission rate within 6 months after treatment in the combined treatment group was lower than that in the other groups(P<0.05).At 5 and 9 days after treatment,the 6-minute walking distance in the combined treatment group was longer than that in the other groups(P<0.05).At 9 days after treatment,the left ventricular ejection fraction(LVEF)in the combined treatment group was higher than that in the other groups(P<0.05),and the level of N-terminal B-type natriuretic peptide(NT-proBNP)in the combined treatment group was lower than that in the other groups(P<0.05).No significant difference was found in the comparison of the occurrence of adverse reactions among the four groups(P>0.05).Conclusion The combina-tion of levosimendan and rhBNP in the treatment of patients with acute heart failure is superior to traditional treatment and monotherapy in early clinical improvement,and dose not increase the incidence of adverse reactions.
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Since the 19th century, the emergence of model systems has helped researchers further understand cellular signaling pathways, identify potential drug targets, and conduct environmental toxicological studies. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect brain biological processes and functions and eventually lead to neurological diseases. However, the brain is a complex and well-organized human organ, which is fundamentally different from any existing model system. Animal models may not be able to completely simulate the human brain in testing the neurotoxicity of environmental pollutants due to species differences. Human brain organoids, generated from human pluripotent stem cells, are emerging model systems for neurotoxicological research in line with the real situation of human body at the level of genome, transcriptome, and metabolome, and provide an effective platform for testing neurotoxicity of environmental toxins. We reviewed the latest development of brain organoids technology and its application in the evaluation of environmental neurotoxins, and provided new insights into the application of brain organoids in environmental neurotoxicology.
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@#Objective To investigate the effects of the long non-coding RNA LOXL1 antisense RNA 1 （LOXL1-AS1） on the apoptosis and inflammatory factor expression of human brain microvascular endothelial cells （HBMECs） induced by oxygen-glucose deprivation （OGD）. Methods HBMECs were divided into control group （normal culture）， OGD group （OGD injury）， OGD+si-NC group （transfection with si-NC plus OGD injury）， OGD+si-LOXL1-AS1 group （transfection with si-LOXL1-AS1 plus OGD injury）， OGD+miR-NC group （transfection with miR-NC plus OGD injury）， OGD+miR-761 group （transfection with miR-761 mimic plus OGD injury）， OGD+si-LOXL1-AS1+negative control group （transfection with si-LOXL1-AS1 and anti-miR-NC plus OGD injury）， and OGD+si-LOXL1-AS1+miR-761 inhibitor group （transfection with si-LOXL1-AS1 and miR-761 inhibitor plus OGD injury）. The expression of LOXL1-AS1 and miR-761 was measured by RT-qPCR. Cell viability was measured using cell counting kit-8. Cell apoptosis was determined by flow cytometry. The expression of B-cell lymphoma/leukemia-2 （Bcl-2） protein and Bcl-2-associated X （Bax） protein was measured by Western blotting. The levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay. Dual luciferase reporter assay was used to detect the complementary binding of LOXL1-AS1 and miR-761. Results Compared with the control group， the OGD group showed significant increases in LOXL1-AS1 expression， the cell apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels and significant decreases in the cell survival rate and Bcl-2 expression （all P<0.05）. After inhibiting LOXL1-AS1， the OGD+si-LOXL1-AS1 group showed significant decreases in LOXL1-AS1 expression， the apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels and significant decreases in the survival rate and Bcl-2 expression， compared with the OGD group and the OGD+si-NC group （all P<0.05）. LOXL1-AS1 targeted the expression of miR-761. After overexpressing miR-761， the OGD+miR-761 group showed significant increases in the survival rate and Bcl-2 expression and significant decreases in the apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels， compared with the OGD+miR-NC group （all P<0.05）. Compared with the OGD+si-LOXL1-AS1+negative control group， the OGD+si-LOXL1-AS1+miR-761 inhibitor group showed significantly decreased survival rate and Bcl-2 expression and significantly increased apoptosis rate， Bax expression， and IL-6， IL-1β， and TNF-α levels （all P<0.05）. Conclusion Inhibiting LOXL1-AS1 expression can up-regulate miR-761 to promote the survival of OGD-induced HBMECs and suppress the cells' apoptosis and expression of inflammatory factors.
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@#Objective To establish and verify a capillary isoelectric focusing-whole column imaging detection(CIEFWCID) method for the analysis of isoelectric point(pI) of recombinant human brain natriuretic peptide.Methods The ampholyte,space-occupying agent,protein concentration,focusing time were optimized by CIEF-WCID method,and the best condition for the detection of recombinant human brain natriuretic peptide was obtained.The repeatability,precision and durability of the developed method were verified,and three batches of recombinant human brain natriuretic peptide produced continuously were analyzed for pI.Results HR AESlyte 8-10.5 was selected as ampholyte,while 25 mmol/L sodium hydroxide as the space-occupying agent;The final concentration of the sample was 87.5 μg/mL and the focusing time was 8min.The relative standard deviation RSD of pI detection was 0.1% after six consecutive injections of the same sample;The RSD of pI detection of six samples was 0.1%;The pI RSD of the main peak was 0.1% at different final concentrations of the sample,and the pI RSD of the sample was 0.1% at different storage time,while the pI markers could not be changed arbitrarily.The pI was detected in three consecutive batches of recombinant human brain natriuretic peptide samples.Conclusion The developed CIEF-WCID method for pI analysis of recombinant human brain natriuretic peptide had good repeatability and precision and might be used for follow-up quality control of recombinant human brain natriuretic peptide.
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Objective To investigate the effect of long non-coding RNA (lncRNA) alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) targeting microRNA (miR) -106b-5p on oxidized low-density lipoprotein (ox-LDL) -induced injury of human brain microvascular endothelial cells. Methods Human brain microvascular endothelial cells (ox-LDL group) were induced by ox-LDL, normal cultured cells were control group (Ctrl); A2M-AS1 overexpression (pcDNAA2M-AS1 group), empty vector (pcDNA group), miR-106b-5p inhibitor (anti-miR-106b-5p group), negative control (anti-miR-NC group), pcDNA-A2M-AS1 with control mimic NC (miR-NC group), pcDNA-A2M-AS1 with miR-106b-5p mimic (miR-106b-5p mimics group) were transfected into cells and treated with ox-LDL, n = 9. Real-time PCR was used to detect the expression levels of A2M-AS1 and miR-106b-5p; Kits were used to detect malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)); Flow cytometry and TUNEL detected apoptosis; Dual luciferase reporter gene assay detected A2M-AS1 and miR-106b-5p targeting; Western blotting detected Bcl-2 and Bax protein expression. Results Compared with the Ctrl group, the expression level of A2M-AS1 in the ox-LDL group decreased, and the activity of SOD and CAT and the protein level of Bcl-2 decreased (P<0.05), while the expression level of miR-106b-5p and the level of MDA increased (P<0.05), and the rate of apoptosis and the protein level of Bax increased (P<0.05). Overexpressing A2M-AS1 or interfering with miR-106b-5p decreased the MDA level, apoptosis rate and Bax protein level after ox-LDL-induced cells, and increased SOD, CAT activity and Bcl-2 protein level (P<0.05). A2M-AS1 targeted miR-106b-5p; upregulation of miR-106b-5p reversed the effect of overexpressed lncRNA A2M-AS1 on ox-LDL-induced injury of human brain microvascular endothelial cells (P < 0.05). Conclusion A2M-AS1 attenuates ox-LDL-induced injury of human brain microvascular endothelial cells by targeting miR-106b-5p.
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Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integra-tion methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bio-informatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.
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Objective To explore the effects of recombinant human brain natriuretic peptide combined with levosimendan on cardiac function,myocardial fibrosis and safety in patients with acute heart failure(AHF).Methods 90 patients with AHF admitted to Changzhou First People's Hospital from May 2021 to April 2023 were randomly divided into the intervention group and the control group.The intervention group was treated with recombinant human brain natriuretic peptide combined with levosimendan,and the control group was treated with levosimendan.Both groups were treated for 14 days.Left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD)and heart rate(HR)were recorded before and after treatment,and mean arterial pressure(MAP)was calculated.The levels of cardiac troponin T(cTnT)and myocardial creatine kinase isoenzyme(CK-MB)were measured in both groups.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and high-sensitivity C-reactive protein(hs-CRP)inflammatory factors were detected in both groups to assess the inflammation of the two groups.Serum soluble human stromal lysin(sST2)and serum fibroblast growth factor-21(FGF-21)levels were detected in both groups to evaluate myocardial fibrosis levels.The incidence of adverse reactions in the two groups was observed to evaluate drug safety.Result A total of 90 AHF patients were included,with 45 cases in the intervention group and 45 cases in the control group.After 14 days of treatment,HR,CK-MB,IL-6,TNF-a,hs-CRP,sST2 and FGF-21 levels of the intervention group were lower than those of control group(P＜0.05),LVEF,cTnT and MAP were higher than those in control group(P＜0.05),and LVEDD level had no statistical difference(P＞0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusions Recombinant human brain natriuretic peptide combined with levosimendan can effectively improve cardiac function and myocardial fibrosis in patients with AHF with good safety.
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BACKGROUND Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.
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Biobanks are set to become the norm. The explosion of new and powerful technologies like genomics and other multiomics has catapulted research from individual laboratories to multi-institutional and international partners. Today, with increasing life span, and the rising incidence of brain diseases, Brain Banks have become an invaluable source for unravelling the pathogenesis of several brain disorders, and develop effective therapies. The article briefly reviews the evolution of brain banking, rise of global networks, with a brief overview of steps involved from donor recruitment, protocols of processing, storage, annotation, and tissue distribution. The ethics of biobanking is one of the most controversial issues in bioethics, the key issues being consent, confidentiality, and commercialisation. Regulatory authorities in different countries and in India, the Indian Council of Medical Research has taken a lead to formulate new ethical guidelines for research involving human participants protecting rights, and well-being of research participants. Although brain banks have been established in the 1960s, in India, the first Brain Bank was established in 1995 at the National Institute of Mental Health and Neurosciences, Bengaluru. Now a network with two more Brain banks is being established in the country. The challenges and benefits of establishing the first Brain Bank as a National Research Facility in India is shared. For optimising available resources and promote brain banking, it is essential for medical professionals, and the public to perceive the crucial advantage in conversion of biological waste into invaluable resources for neuroscience. This will be the greatest “gift of hope” that we can offer for the future generations to overcome hitherto untreatable disorders such as dementias.
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Background: Everyone has a different brain programming some people have a brilliant concentration but some people struggle to focus on things or to pay attention. This, research is focused on the importance of concentration for learners as the previous studies also concluded that higher levels of concentration are vulnerable to distractions. Hence this research is intended to assess the reports generated from the Aimtest tool administered by 8 Infinity Education Research group in India with the end view of identifying its implication to enhance the human concentration level. Materials and Methods: This prospective study operates on evocative research method which involved the use of documentary analysis, questionnaires and interviews with voluntary opted respondents carried by researchers' approach and analysis pertaining to the content of the data. In this pilot study, we recruited 159 individuals age 8 to 20 yearsResult: between the academic standard levels 4th to 12th who were chosen after consent for this assessment. The Aimtest calculated their Memory, concentration level and, reading speed with the proven formulas. We have found overall 83.64% satisfaction rate among all the categories. Based on the descriptive research our findings suggestConclusion: that this tool can be used to enhance the concentration level as well as it can also be embodied in academic institutions to improve on the learning ability of students.
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OBJECTIVE：To observe the clinical effect and safety of recombinant human brain natriuretic peptide （rhBNP） combined with levosimendan in the treatment of acute decompensated heart failure （ADHF）complicated with renal insufficiency. METHODS：A total of 156 patients with ADHF complicated with renal insufficiency admitted to the Dept. of Cardiology in the Affiliated Hospital of Southwest Medical University during Jan.-Dec. 2019 were randomly divided into rhBNP group ，levosimendan group and combination group ，with 52 patients in each group. All patients received rountine treatment. On this basis ，rhBNP group was given rhBNP for injection [after 1.5 μg/kg intravenous pulse injection，intravenous dripping for 24 h with 0.007 5 μg（/ kg· min）]；leosimendan group was given Leosimendan injection 12.5 mg [intravenous dripping for 1 h with 6-12 μg（/ kg·min），then intravenous dripping for 23 h with 0.1 μg（/ kg·min）]. Combination group received drug combination according to the administration method of single drug group. Three groups received treatment for consecutive 7 d. Cardiac function indexes [heart rate （HR），left ventricular ejection fraction （LVEF），left ventricular end-diastolic diameter （LVEDD）]，mean arterial pressure （MAP），pulmonary capillary pressure （PCWP），renal function indexes [estimated glomerular filtration rate （eGFR），serum creatinine （Scr）]，serum levels of cystatin C （Cys-c）and amino-terminal brain natriuretic peptide precursor （NT-proBNP）were observed in 3 groups before and after treatment. Clinical efficacy and the occurrence of ADR were recorded. RESULTS ：Three cases withdrew from the study in rhBNP group and 1 case in levosimendan group ；152 cases completed the study. Before treatment ，there was no statistical significance in cardiac function indexes ，MAP，PCMP，renal function indexes or serum levels of Cys-C and NT-proBNP among 3 groups（P＞0.05）. After treatment ，the HP ，MAP，PCWP and serum level of NT-proBNP in 3 group as well as serum level of Cys-C in combination group were decreased significantly （P＜0.05）；the LVEF in 3 group as well as the eGFR and Scr level in levosimendan group and combination group were significantly increased （P＜0.05），compared with before treatment ；above indexes of combination group were significantly better than those of rhBNP group and levosimendan group （P＜0.05）. Total effective rate of combination group was 94.23％ ，which was significantly higher than those of rhBNP group （77.55％）and levosimendan group （76.47％）（P＜0.05）. There was no significant difference in the incidence of ADR among 3 groups（P＞ 0.05）. CONCLUSIONS ：rhBNP combined with levosimendan in the treatment of ADHF complicated with renal insufficiency can significantly increase the clinical efficacy ，and improve cardiac and renal function but don ’t increase the incidence of ADR.
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According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.
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Animales , Humanos , Péptidos beta-Amiloides , Barrera Hematoencefálica , Medicamentos Herbarios Chinos , Células EndotelialesRESUMEN
BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.
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Humanos , Daño por Reperfusión/metabolismo , Hipoxia Encefálica/metabolismo , MicroARNs/fisiología , MicroARNs/genética , ARN Circular , Oxígeno , Encéfalo , Apoptosis , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Células Endoteliales , ARN Largo no Codificante , Glucosa/metabolismo , InflamaciónRESUMEN
Purpose: Enterovirus 71 (EV71) is one of the main pathogens causing hand, foot and mouth disease, which could even induce severe brain damage in some patients. As the underlying mechanism of the invasion and replication process still remains largely unknown, we investigated the role of candidate proteins expressed during EV71 invasion in human brain microvascular endothelial cells (HBMECs) to delineate the pathophysiological mechanism of EV-71 infection. Materials and Methods: Ninety-one candidate EV71-associated proteins which could bind the major capsid protein (viral protein 1 [VP1]) of EV71 on the HBMEC were identified by applying an analysis of glutathione-S-transferase pull-down coupling with liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). Seventy-eight kDa glucose-regulated protein 78 (GRP78) binding to the VP1 protein was further validated by co-immunoprecipitation, immunofluorescence and western blot analysis. To explore the role of GRP78 in EV71 infection, GRP78 was knocked down and overexpressed in HBMEC and was verified by TCID50 assay. Results: LC-ESI-MS/MS-identified 91 proteins were subjected to gene ontology analysis, and on molecular and biological function analysis revealed GRP78 act as an important binding protein in mediating EV71 infection. In addition, immunofluorescence demonstrated the co-localisation of GRP78 and VP1 in cytoplasm of the infected HBMEC. The TCID50 assay showed that knockdown of GRP78 could attenuate the replication capacity of EV71 in HBMEC, and the overexpression could increase the virus titre in HBEMC at 24 h post-infection suggesting that GRP78 was associated with the replication capacity of EV71 in HBMEC. Conclusion: These findings provided evidence that GRP78 plays an important role during the progression of EV71 infection as a mediator in HBMEC.
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Objective To investigate the clinical effects of levosimmentan combined with freeze-dried recombinant human brain natriuretic peptide in elderly patients with heart failure. Methods Eighty patients with heart failure diagnosed in our hospital from January 2015 to January 2018 were selected as subjects. According to the random number table prepared in Excel 2007,40 patients in the experimental group and the control group were given. For basic treatments such as diuresis,the experimental group was treated with levosimtan combined with lyophilized recombinant human brain natriuretic peptide,and the control group was treated with levosimtan and dobutamine. The left ventricle of the two groups before and after treatment was compared. End-diastolic period (LVEDD),left ventricular ejection fraction(LVEF),cardiac index(CI),stroke volume(SV),serum cystatin C (Cys-C),amino terminal brain natriuretic peptide precursor(NT-proBNP),mean arterial pressure(MAP), pulmonary capillary pressure(PCWP). Results Before treatment,the differences of LVEDD,LVEF,CI and SV levels between the experimental group and the control group were not statistically significant(P > 0.05). After treatment,the LVEDD of the experimental group was significantly lower than that of the control group(P < 0.05).The LVEF,CI and SV values in the experimental group were significantly higher than those in the control group (P < 0.05). There was no significant difference in serum Cys-C and NT-proBNP levels between the experimental group and the control group before treatment(P > 0.05). After treatment,the serum levels of Cys-C and NT-proB-NP in the experimental group were significantly lower than those in the control group(P < 0.05). Before treatment,the difference of MAP and PCWP levels between the experimental group and the control group was not statistically significant(P > 0.05). After treatment,the MAP and PCWP levels in the experimental group were significantly lower than those in the control group(P < 0.05). The incidence of adverse reactions in the experimental group was 10.00％ and the difference between the control group and the control group was not statistically significant(P > 0.05). Conclusions Levosimmentan combined with freeze-dried recombinant human brain natriuretic peptide in patients with senile heart failure can significantly improve cardiac function,reduce Cys-C,NT-proBNP levels,and improve hemodynamic parameters.
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In this study, the distribution of five Alzheimer's disease (AD)-related single nucleotide polymorphisms (SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs, clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC) Human Brain Bank. APOE ε4 (OR = 4.482, P = 0.004), the RS2305421 GG genotype (adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype (adjusted OR = 2.375, P = 0.028) were associated with a higher score on the ABC (Aβ plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD, the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína ADAM10 , Genética , Enfermedad de Alzheimer , Genética , Patología , Secretasas de la Proteína Precursora del Amiloide , Genética , Antiportadores , Genética , Apolipoproteína E4 , Genética , Pueblo Asiatico , Genética , Encéfalo , Patología , Disfunción Cognitiva , Genética , Patología , Predisposición Genética a la Enfermedad , Proteínas de la Membrana , Genética , Polimorfismo de Nucleótido SimpleRESUMEN
Advances in cellular and molecular biology underpin most current therapeutic advances in medicine. Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes.
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Humanos , Envejecimiento , Patología , Fisiología , Investigación Biomédica , Métodos , Encéfalo , Patología , Enfermedades Neurodegenerativas , Patología , Terapéutica , Bancos de Tejidos , Conservación de TejidoRESUMEN
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
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Humanos , Encéfalo , Encefalopatías , Quimioterapia , Técnicas de Cultivo de TejidosRESUMEN
Objective To evaluate the influence of fluoride on mitochondrial membrane potential of neuroblastoma SH-SY5Y cells,and on the expression levels of mitochondrial proteins mitofusion 1 (Mfn1) and fission 1 (Fis1).Methods A stable and feasible culture method of SH-SY5Y cells in vitro was established with different concentration of sodium fluoride [0.0 (control),0.4,2.0 and 4.0 mmol/L],and various periods exposure of 6,12,24,48 h;the mitochondrial membrane potential of SH-SY5Y cells was detected by mitochondrial membrane potential assay kit (JC-1);and the expression levels of Mfn1 and Fis1 proteins were detected by Western blotting.Results Compared with the control group (1.63 ± 0.18,1.13 ± 0.15,1.30 ± 0.02) for various periods exposure (6,12,48 h),the red/green fluorescence ratios of the mitochondrial membrane potential of SH-SY5Y cells exposed to 2.0 and 4.0 mmol/L of sodium fluoride were decreased significantly (1.01 ± 0.10,0.80 ± 0.04;0.75 ± 0.13,0.62 ± 0.10;0.82 ± 0.01,0.56 ± 0.04,P ＜ 0.05);compared with the control group (0.93 ± 0.03,1.05 ± 0.07,1.17 ± 0.04) for various periods exposure,the expression levels of mitochondrial Mfn1 protein were decreased significantly in 0.4,2.0,4.0 mmol/L sodium fluoride groups (6,12,48 h:0.75 ± 0.02,0.65 ± 0.05,0.57 ± 0.06;0.83 ± 0.06,0.79 ± 0.06,0.69 ±0.06;0.98 ± 0.05,0.73 ± 0.07,0.62 ± 0.09,P ＜ 0.05).Compared with the control group (0.90 ± 0.05) for exposure time 12 h,the expression levels of Fis1 protein were increased significantly in 2.0,4.0 mmol/L sodium fluoride groups (1.14 ± 0.06,1.23 ± 0.06,P ＜ 0.05).Conclusions The mitochondrial membrane potential and the expression levels of mitofusion 1 and fission 1 of SH-SY5Y cells treated with fluoride are abnormal,which might be associated with the theory of nerve cell damage from high oxidative stress.
RESUMEN
Objective To investigate the influence of inhibited gene expression of fisson 1 (Fis1) gene on the level of Fis1,mitofusin 1 (Mfn1) and mitochondrial membrane potential in SH-SY5Y cells with fluorine,to study the role of mitochondrial dynamic balance in the pathogenesis of chronic fluorosis.Methods SH-SY5Y cells were cultured in vitro,when adherent cells entered the logarithmic phase,using a group design,they were divided into four groups:blank control group (control),fluoride group [2 mmol/L sodium fluoride (NaF)],fluoride negative control group (2 mmol/L NaF + non-specific siRNA) and the gene-silencing group (2 mmol/L NaF + specific siRNA-Fis1).The protein expression levels of Fis1 and Mfn1 were measured by Western blotting;the mRNA expression levels of Fis1 and Mfn1 were measured by Real-time PCR;and the levels of the mitochondrial membrane potential was detected by mitochondrial membrane potential detection kit.Results Compared with control (1.37 ± 0.18,1.00 ± 0.04;1.57 ± 0.19,1.00 ± 0.04;1.00 ± 0.10),the expression levels of Fisl protein (1.72 ± 0.04) and mRNA (1.48 ± 0.13) in fluoride group were increased,the expression levels of Mfn1 protein (0.87 ± 0.02) and mRNA (0.69 ± 0.07) in fluoride group were decreased,the level of mitochondrial membrane potential (0.76 ± 0.13) was decreased (P ＜ 0.05).Compared with control,the expression levels of Fis1 protein (0.79 ± 0.07) and mRNA (0.06 ± 0.03) in gene-silencing group were decreased,the expression levels of Mfn1 protein (1.71 ± 0.04) and mRNA (1.52 ± 0.05) in gene-silencing group were increased (P ＜ 0.05),the level of mitochondrial membrane potential (0.94 ± 0.01) was decreased.Compared with fluoride group,the expression levels of Fis1 protein and mRNA in gene-silencing group were decreased,the expression levels of Mfn1 protein and mRNA in gene-silencing group were increased,the level of mitochondrial membrane potential in gene-silencing group was increased (P ＜ 0.05).Conclusion Gene expression inhibition of Fis1 gene can reduce the mitochondrial division and damage of mitochondrial membrane potential in SH-SY5Y cells induced by fluoride.