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BACKGROUND: Plant HSP20s are not only synthesized in response to heat stress but are also involved in plant biotic and abiotic stress resistance, normal metabolism, development, differentiation, survival, ripening, and death. Thus, HSP20 family genes play very important and diverse roles in plants. To our knowledge, HSP20 family genes in peach have not yet been characterized in detail, and little is known about their possible function in the development of red flesh in peach. RESULTS: In total, 44 PpHSP20 members were identified in the peach genome in this study. Forty-four PpHSP20s were classified into 10 subfamilies, CI, CII, CIII, CV, CVI, CVII, MII, CP, ER, and Po, containing 18, 2, 2, 10, 5, 1, 1, 2, 1, and 2 proteins, respectively. Among the 44 PpHSP20 genes, 6, 4, 4, 3, 7, 11, 5, and 4 PpHSP20 genes were located on chromosomes 1 to 8, respectively. In particular, approximately 15 PpHSP20 genes were located at both termini or one terminus of each chromosome. A total of 15 tandem PpHSP20 genes were found in the peach genome, which belonged to five tandemly duplicated groups. Overall, among the three cultivars, the number of PpHSP20 genes with higher expression levels in red flesh was greater than that in yellow or white flesh. The expression profiling for most of the PpHSP20 genes in the red-fleshed 'BJ' was higher overall at the S3 stage than at the S2, S4-1, and S4-2 stages, with the S3 stage being a very important period of transformation from a white color to the gradual anthocyanin accumulation in the flesh of this cultivar. The subcellular localizations of 16 out of 19 selected PpHSP20 proteins were in accordance with the corresponding subfamily classification and naming. Additionally, to our knowledge, Prupe.3G034800.1 is the first HSP20 found in plants that has the dual targets of both the endoplasmic reticulum and nucleus. CONCLUSIONS: This study provides a comprehensive understanding of PpHSP20s, lays a foundation for future analyses of the unknown function of PpHSP20 family genes in red-fleshed peach fruit and advances our understanding of plant HSP20 genes.
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Prunus persica , Genoma de Planta , Genes de Plantas/genética , Resposta ao Choque Térmico , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Frutas/genética , FilogeniaRESUMO
Land use change and ecological sensitivity studies are relevant to the dynamic stability of the overall regional ecological environment. In this study, Nanyang City, a South-North Water Transfer water source area, was used as the study area to analyse land use changes and landscape pattern changes in Nanyang City from 1990 to 2020 based on land use data. Hierarchical analysis (AHP method) was used and combined with six sensitivity factors to conduct a multi-factor comprehensive ecological sensitivity evaluation of Nanyang City. The results show that: (1) between 1990 and 2020, the transfer of water and construction land in Nanyang City was larger, increasing by 30.25% and 99.56% respectively, with a small decrease in the area of cultivated land and a small increase in the area of forest land; the overall rate of land use change in Nanyang City during the 30-year period was first slow and then fast. (2) At the level of patch types, the fragmentation of cultivated land and construction land is the highest; during the study period, the overall fragmentation of the study area tends to decrease; at the level of landscape, each landscape type develops in the direction of equilibrium. (3) The ecological sensitivity increases gradually from the urban cluster in the central plain area to the periphery, with the highly sensitive areas distributed in the water area, the medium sensitive areas in the mountainous area, and the low sensitive areas and insensitive areas in the cultivated land and town planning area.
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Conservação dos Recursos Naturais , Ecossistema , Água , Monitoramento Ambiental/métodos , Florestas , Cidades , ChinaRESUMO
BACKGROUND: Pediatric meningioma with YAP1 fusion is a rare subset of meningiomas. Currently, there are lack of integrated clinical, radiological, and pathological features on this subset. Here, we reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant and reviewed the relevant literature. CASE PRESENTATION: We presented a case of 12-year-old boy with meningioma adjacent to the superior sagittal sinus and falx. Simpson grade II gross total resection was performed after diagnosis. Pathologically, he was diagnosed as WHO grade I meningothelial meningioma with rhabdoid features. A next-generation sequencing-based gene panel was performed to determine the molecular features for potential treatment, and a novel MAML2-YAP1 fusion break point was identified. CONCLUSION: Pediatric meningioma with the fusion of YAP1 and MAML2 genes is more likely to have pathological features of rhabdiod cells, which needs to be validated in large-scale studies for exploring better treatment under the integrated diagnosis.
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Neoplasias Meníngeas , Meningioma , Masculino , Criança , Humanos , Meningioma/diagnóstico por imagem , Meningioma/genética , Fatores de Transcrição/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/genética , Transativadores/genéticaRESUMO
BACKGROUND: Peach (Prunus persica) is an important fruit crop that generally softens rapidly after harvest resulting in a short shelf-life. By contrast, stony hard (SH) peach fruit does not soften and hardly produces ethylene. To explore the candidate genes responsible for the SH phenotype, a high-density genetic map was constructed by restriction-site associated DNA sequencing technology. RESULTS: In the present study, the linkage map consisted of 1310 single nucleotide polymorphism markers, spanning 454.2 cM, with an average marker distance of 0.347 cM. The single nucleotide polymorphisms were able to anchor eight linkage groups to their corresponding chromosomes. Based on this high-density integrated peach linkage map and two years of fruit phenotyping, two potential quantitative trait loci for the SH trait were identified and positioned on the genetic map. Additionally, Prupe.6G150900.1, a key gene in abscisic acid (ABA) biosynthesis, displayed a differential expression profile identical to the ABA accumulation pattern: mRNA transcripts were maintained at a high level during storage of SH peaches but occurred at low levels in melting fruit. CONCLUSION: Thus Prupe.6G150900.1 might play a crucial role in the SH phenotype of peach in which ABA negatively regulates ethylene production. Also, this high-density linkage map of peach will contribute to the mapping of important fruit traits and quantitative trait loci identification.
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Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Prunus persica/genética , Locos de Características Quantitativas , Perfilação da Expressão Gênica , Mapeamento por Restrição , Análise de Sequência de DNARESUMO
Hebi is located in the northern part of China's Henan Province and is a typical receiving area for China's South-to-North Water Diversion Project. The assessment of habitat quality and water yield over a long time series is important for evaluating the stability of ecosystem services in Hebi and other receiving areas and for maintaining ecological security and promoting sustainable development. This paper aims to evaluate and dynamically analyse habitat quality and water yield in Hebi, and analyses the characteristics of changes in spatial and temporal patterns of land cover types, habitat quality and water yield in Hebi over the past 20 years, using 2000, 2005, 2010, 2015 and 2020 as horizontal years. The results indicate that: (1) During the study period, the overall land use type in Hebi City has been constantly changing, with the most significant conversion from arable land to other land types; combined with its landscape pattern index, Hebi City has a general characteristic of significant landscape fragmentation and complexity in land use. (2) Habitat quality in Hebi shows an overall trend towards better development, with water availability decreasing and then increasing; the zoning of ecosystem services in Hebi is divided into three classes: superior, good and general, with the area covered by the superior and general classes expanding year by year. (3) Correlation analysis by SPSS software shows that the correlation between habitat quality and landscape pattern index is greater than the correlation between habitat quality and climate change. Additionally, the correlation between water availability and climate change is greater than the correlation between water availability and landscape pattern index.
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Conservação dos Recursos Naturais , Ecossistema , China , Conservação dos Recursos Naturais/métodos , Abastecimento de Água , Água , Monitoramento Ambiental/métodosRESUMO
Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.
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Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme branching from glycolysis in the three-step serine biosynthetic pathway. Recent evidence has shown that PHGDH is amplified in human breast cancer and melanoma and plays a key role in cancer metabolism. However, PHGDH expression in glioma and a potential non-metabolic role in tumorigenesis have not been reported. We analyzed PHGDH levels in specimens from glioma patients and found that PHGDH, although negative in normal brain tissues, was highly expressed in astrocytic tumors and increasingly expressed in more aggressive cancer types. Inhibition of PHGDH expression in glioma cells downregulated the expression of VEGF, MMP-2, CHK2 and cyclin D1 and reduced glioma cell proliferation, invasion and tumorigenicity in vitro and in vivo. Interestingly, we found that the oncogenic transcription factor FOXM1 was also downregulated in PHDGH-silenced glioma cells. Using LC/LC MS analysis, we identified PHGDH as a novel binding partner of FOXM1. PHGDH interacted with and stabilized FOXM1 at the protein level, promoting the proliferation, invasion and tumorigenicity of glioma cells. Our data identified PHGDH as a potential prognostic marker of glial brain tumors and identified a non-metabolic role for PHGDH in glioma tumorigenesis, providing a novel angle of targeting the PHGDH-FOXM1 axis in future brain tumor therapy.
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Neoplasias Encefálicas/enzimologia , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Glioma/enzimologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Gliceraldeído-3-Fosfato Desidrogenases/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Transplante de Neoplasias/métodos , Interferência de RNA/fisiologia , RNA Mensageiro/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Ensaio Tumoral de Célula-TroncoRESUMO
Accurate medium and long-term runoff forecasts play a vital role in guiding the rational exploitation of water resources and improving the overall efficiency of water resources use. Machine learning is becoming a common trend in time series forecasting research. Least squares support vector machine (LSSVM) and grey model (GM(1,1)) have received much attention in predicting rainfall and runoff in the last two years. "Decomposition-forecasting" has become one of the most important methods for forecasting time series data. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) decomposition method has powerful advantages in dealing with nonlinear data. Least squares support vector machine (LSSVM) has strong nonlinear fitting ability and good robustness. Gray model (GM(1,1)) can solve the problems of little historical data and low serial integrity and reliability. Based on their respective advantages, a combined CEEMDAN-LSSVM-GM(1,1) model was developed and applied to the runoff prediction of the lower Yellow River. To verify the reliability of the model, the prediction results were compared with the single LSSVM model, the CEEMDAN-LSSVM model and the CEEMDAN-support vector machines (SVM)-GM(1,1). The results show that the combined CEEMDAN-LSSVM-GM(1,1) model has a high accuracy and the prediction results are better than other models, which provides an effective prediction method for regional medium and long-term runoff prediction and has good application prospects.
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Peach (Prunus persica (L.) Batsch) is a highly desirable fruit that is consumed around the world. However, the peach fruit is highly perishable after harvest, a characteristic that limits the distribution and supply to the market and causes heavy economic losses. Thus, peach fruit softening and senescence after harvest urgently need to be addressed. In the current study, transcriptomic analysis was performed to identify candidate genes associated with peach fruit softening and senescence, comparing peach fruit from cultivars with different flesh textures, namely melting and stony hard (SH) flesh textures during storage at room temperature. The mitogen-activated protein kinase signaling pathway-plant and plant hormone signal transduction pathways were associated with peach fruit softening and senescence according to the Venn diagram analysis and weighted gene co-expression network analysis. The expression levels of seven genes, including Prupe.1G034300, Prupe.2G176900, Prupe.3G024700, Prupe.3G098100, Prupe.6G226100, Prupe.7G234800, and Prupe.7G247500, were higher in melting peach fruit than in SH peach fruit during storage. Furthermore, the SH peach fruit softened rapidly after 1-naphthylacetic acid treatment, during which the levels of expression of these seven genes, determined by a quantitative reverse transcription polymerase chain reaction, were strongly induced and upregulated. Thus, these seven genes may play essential roles in regulating peach fruit softening and senescence.
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To investigate the peach fruit flesh types (soft-melting, hard-melting, stonyhard and non-melting) and harvest maturity level suitable for near-freezing temperature storage (NFTS), eight peach cultivars that had four flesh types were used as test materials. Changes in fruit respiration intensity and ethylene release rates, as well as the differences in quality indexes, such as soluble solids content (SSC), firmness, color difference, pigment content, soluble sugar and organic acid component content, of three fruit maturity levels (70%, 80% and 90% maturity) under NFTS conditions were analyzed and compared. The fruit quality indexes of peach having different maturity levels and flesh types changed little during NFTS. The SSC and total sugar content of hard-melting and stonyhard peach fruit were higher than those of other flesh types during NFTS. Those fruit maintained greater firmness at the end of the storage period. The differences in respiration intensity and ethylene release rate were small, but for fruit coloring, hard-melting fruit performed better than stonyhard fruit. The 80%, compared with the 90%, maturity stage maintained more fruit moisture, had less fruit mass loss and maintained a greater edible firmness. It effectively impeded the fruit senescence process and was the most suitable maturity for NFTS. Thus, the hard-melting peach maintained the highest commercial value and desirable storage characteristics under NFTS conditions, and its 80% maturity level was the most suitable for NFTS.
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Background: Most bone marrow mesenchymal stem cell (BMSC) death is caused by the harsh ischemia and hypoxic microenvironment, which impacts the therapeutic effects of transplanted BMSCs. Fibronectin type III domain-containing protein 5 (FNDC5) and its cleaved product, irisin, are reportedly involved in cerebral protective effect. Research into whether FNDC5 plays a key role in the survival rate of BMSCs and cerebral infarction (CI) remains inadequate. The present study aimed to clarify the protective role of FNDC5 on the low viability of transplanted BMSCs and improve CI treatment outcomes. Methods: A lentivirus vector, which drives the expression of FNDC5, was constructed and used to transfect BMSCs. Cell Counting Kit-8 (CCK8), flow cytometry, immunofluorescence, and western blot were performed to evaluate the function of FNDC5-overexpressing BMSCs (BMSCs-OE-FNDC5) exposed to hypoxic and serum deprivation (H/SD) stress. Transmission electron microscopy (TEM) was used to monitor autophagy. In addition, BMSCs were engrafted into a middle cerebral artery occlusion (MCAO) rat model with or without FNDC5-overexpression (OE-FNDC5). The survival rate of transplanted BMSCs was evaluated by 5-ethynyl-2'-deoxyuridine (EdU) labeling. The CI volume was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Results: H/SD stress caused increased cell autophagy, apoptosis, and decreased cell viability of BMSCs, while OE-FNDC5 alleviated these injuries. The in vivo results showed that transplantation of BMSCs-OE-FNDC5 reduced the infarct volume in the rat MCAO model. Furthermore, OE-FNDC5 decreased neuronal apoptosis. The improved therapeutic efficacy of BMSCs-OE-FNDC5 may be attributable to the obviously increased cell survival number after transplantation. Conclusions: These results indicated that FNDC5 overexpression promotes BMSC survival in a CI model, which might provide a potential therapeutic target.
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BACKGROUND AND PURPOSE: We present detailed results of using Neuroform stent-assisted coil embolization to treat complex cerebral aneurysms over a three-year period. MATERIAL AND METHODS: Only patients who underwent Neuroform stent-assisted coil embolization were included in this study. We assessed patients' history, aneurysm morphology, indications for stenting, and technical details of the procedures, as well as complications and the midterm follow-up data. RESULTS: This study included 26 patients with 39 aneurysms. A total of 32 of 39 aneurysms were treated by Neuroform stent-assisted embolization (SAC), whereas 3 aneurysms were stented without coiling, 2 aneurysms coiled without stenting and 2 aneurysms surgically clipped. The indications for use of stent included broad-neck aneurysms (n = 28), giant or large aneurysms (n = 6), and fusiform aneurysms (n = 5). Of the 32 aneurysms treated with Neuroform SAC, we achieved complete (100%) and near complete (> 95%) occlusion in 27 aneurysms, and partial (< 95%) occlusion in 5 aneurysms. Follow-up angiographic data available in 22 of 32 aneurysms treated with Neuroform SAC (68.7%) demonstrated recanalization in 3 aneurysms (13.6%), and stable occlusion in 19 aneurysms (86.4%). There was no delayed progressive embolization or in-stent stenosis. CONCLUSIONS: Direct and midterm follow-up results confirmed that Neuroform stent-assisted coil embolization was a safe and effective technique in the treatment of complex cerebral aneurysms. Although clinically significant complications were uncommon and the evaluation at midterm follow-up is encouraging, further studies need to assess the long-term stability and durability of the stent.
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Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Stents , Adulto , Angiografia Cerebral/métodos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Hypertension is one of the critical risk factors of cerebrovascular disease. Caveolin1 (Cav1) has been suggested to be involved in the development of hypertension; however, the underlying mechanism remains largely unknown. Therefore, the present study aimed to investigate the mechanism underlying Cav1 in hypertension. In the present study, the hypertension model was induced by infusion of angiotensin II (AngII) in rats. Cell Counting Kit8 assay was used to detect the viability of human umbilical vein endothelial cells (HUVECs). Flow cytometry was used to determine the apoptosis of HUVECs. Transmission electron microscopy was utilized to address the thickness of the vessel walls. Reverse transcriptionquantitative PCR, western blotting and immunofluorescence staining were used to assess the mechanism of cav1/Notch1 involved in hypertensive vascular remodeling. In the present study, an AngIIinduced hypertension model was successfully established in rats. With this model, it was found that the expression levels of cav1 and Notch1 were significantly increased in brain tissues in the hypertension group compared with the shamoperated group. In cultured HUVECs, knockdown of cav1 regulated AngIIinduced HUVEC viability and apoptosis, and modulated hypertensive vascular remodeling, which was mediated by the Notch pathway. The data of the present study demonstrated that the cav1/Notch signaling plays an important role in the regulation of AngIIinduced hypertension and vascular remodeling.
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Angiotensina II/efeitos adversos , Caveolina 1/metabolismo , Hipertensão/metabolismo , Remodelação Vascular/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Caveolina 1/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , Ratos , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para CimaRESUMO
The inhibitor of kappa B kinase epsilon is overexpressed in glioma and plays antiapoptotic role via activating nuclear factor-kappa B. microRNA-98 can suppress glioma, modulate the activities of nuclear factor-kappa B, and bind to the 3'-untranslated region of inhibitor of kappa B kinase epsilon messenger RNA. This study was aimed to investigate the modulation of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B by microRNA-98 in glioma. The results indicated that microRNA-98 was downregulated in glioma cell lines and human glioma tissues. Overexpression of microRNA-98 in U87MG and T98G glioma cells significantly increased the apoptosis induced by ultraviolet irradiation and suppressed nuclear factor-kappa B luciferase activity, nuclear factor-kappa B p50 subunit expression, and B-cell lymphoma-2 (Bcl-2) expression in glioma cells. Silencing inhibitor of kappa B kinase epsilon decreased the expression of nuclear factor-kappa B p50 subunit and the luciferase activity of nuclear factor-kappa B, while the nuclear factor-kappa B activity could be significantly retrieved when inhibitor of kappa B kinase epsilon was expressed in microRNA-98-transfected cells. These findings indicated that microRNA-98 could promote apoptosis of glioma cells via inhibiting inhibitor of kappa B kinase epsilon/nuclear factor-kappa B signaling and presented a novel regulatory pathway of microRNA-98 by direct suppression of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B expression in glioma cells.
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Glioma/genética , Quinase I-kappa B/genética , MicroRNAs/genética , Subunidade p50 de NF-kappa B/genética , Apoptose/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Humanos , Masculino , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais/genética , Fator de Transcrição RelA/genéticaRESUMO
MicroRNAs (miRNAs) are a group of non-coding RNAs that have functions in post-transcriptional gene regulation in plants. Although the most important economic component of peach trees (Prunus persica) is the fruit, not much is known about miRNAs in this organ. In this study, miRNAs and their targets were identified and characterized from libraries of small RNAs of peach fruit through Solexa based-sequencing and bioinformatics approaches. A total of 557 known peach miRNAs belonging to 34 miRNA families were identified, and some of these miRNAs were found to be highly conserved in at least four other plant species. Using the most current criteria for miRNA annotation, 275 putative novel miRNAs were predicted, and the sequencing frequencies of these novel miRNAs were less than those of the conserved miRNAs. In total, 3959 and 1614 target genes for 349 known and 193 novel miRNAs, respectively, were predicted with the criteria that a single target gene can be targeted by different miRNAs and that a single miRNA can also have a large number of target genes. Three targets were even found to be targeted by 13 novel miRNAs that contained the same complete miRNA sequence at different locations and had different scaffolds. The proteins predicted to be targeted by the miRNAs identified in this study encompass a wide range of transcription factors and are involved in many biological processes and pathways, including development, metabolism, stress responses and signal transduction. A total of 115 and 101 target genes were identified to be cleaved by 60 known miRNAs and 27 novel miRNAs through degradome sequencing, respectively. These miRNAs induce cleavage of their targets precisely at the position between nucleotides 10 and 11 of the miRNA sequences from the 5' to the 3' end. Thirty conserved miRNAs and 19 novel miRNAs exhibited differential expression profiles in the peach, and the expression patterns of some miRNAs appeared to be tissue- or developmental stage-specific. The findings of this study provide an important basis for the analysis of miRNAs, their targets and the functions of these targets in peach fruit.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Prunus persica/genética , RNA de Plantas/genéticaRESUMO
BACKGROUND: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM. METHODS: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs). Further, in an animal study, chronic cerebral hypoperfusion model rats were analyzed for the expression of SDF-1 and HIF-1. CXCR4 antagonist, AMD3100, was also used to detect its effects on cerebral vasculogenesis and SDF-1 expression. RESULTS: Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression. Cerebral AVM patients also had higher level of EPCs and SDF-1. In chronic cerebral hypoperfusion rats, SDF-1, HIF-1, and CD45 expressions were elevated. The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls. CONCLUSION: The SDF-1/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in cerebral AVM lesions, possibly via the recruitment of bone marrow EPCs.
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The relationship between single nucleotide polymorphism (SNP) of interleukin-17 (IL-17A), transforming growth factor ß (TGF-ß), as well as its receptor (TGFR-ß2) and susceptibility to intracerebral hemorrhage in patients with brain arteriovenous malformation (BAVM) was investigated in the present study. A total of 53 patients with BAVM and 120 healthy controls were recruited, all of whom were Han Chinese from South China. There were no statistically significant differences in the IL-17A-197 guanine/adenine (G/A) or TGF-ß1-509 cytosine/thymine (C/T) genotypes or gene frequencies between BAVM patients and controls (p>0.05), but the gene frequency of the TGFR-ß2-875 A/G genotype in patients with BAVM was significantly higher (p<0.05). Furthermore, the frequencies of the G allele of IL-17A-197 G/A and TGFR-ß2-875 A/G in BAVM patients with hemorrhage were higher than those without hemorrhage. TGFR-ß2-875 G/G genotype is a risk factor for BAVM, and the IL-17A-197 G/A and TGFR-ß2-875 A/G genotype is closely related to hemorrhage risk for patients with BAVM.
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Predisposição Genética para Doença , Interleucina-17/genética , Malformações Arteriovenosas Intracranianas/genética , Hemorragias Intracranianas/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Fator de Crescimento Transformador beta1/genética , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Testes Genéticos , Genótipo , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Masculino , Pessoa de Meia-Idade , Receptor do Fator de Crescimento Transformador beta Tipo II , Adulto JovemRESUMO
OBJECTIVE: To observe the clinical and pathological characteristics of brain arteriovenous malformations (BAVM) embolized with the non-adhesive aqueous embolic agent Onyx and evaluate its application in comprehensive treatment of BAVM. METHODS: Thirty-four patients underwent BAVM embolization using Onyx, and their clinical manifestations, architecture of the malformed vessels, emblization procedure, and complications associated with the procedures were recorded. The resected tissues after embolization with Onyx were observed with electron microscope, and the prognosis of the patients was estimated with modified Rankin Score (mRS). RESULTS: These patients included 21 male and 13 female patients with a mean age of 30.45-/+11.81 years and an estimated mean size of the nidus of 3.98-/+1.43 cm. The patients received a total of 52 endovascular treatment procedures with Onyx to embolize 86 feeding pedicals, which resulted in an average estimated size reduction of the nidus of (72.35-/+21.26)%. Complications associated with the procedure occurred in 7 patients, and 23 patients received surgical resection or radiosurgery after embolization. Follow-up of the patients for 6 months to 4 years showed that the mRS was below 3 in 32 cases and > or =3 in 2 cases. Vasodilatation, brain tissue edema surrounding the nidus, and inflammatory cell infiltration were observed in the resected tissues after embolization. In some major feeding pedicals, thrombus recanalization was observed after embolization with Onyx (diameter> or =3 mm). CONCLUSION: Endovascular treatment of BAVM with Onyx can achieve high occlusion rate, enhance the safety of operation and radiosurgery, and improve the clinical prognosis of the patients.