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Amyloid-ß1-42 (Aß1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-ß (Aß)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aß1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aß1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aß1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aß1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aß-induced neuronal damage in AD.
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Enfermedad de Alzheimer , MicroARNs , Neuroblastoma , Humanos , MicroARNs/genética , Línea Celular Tumoral , Péptidos beta-Amiloides/toxicidad , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Apoptosis/genética , Fragmentos de Péptidos/farmacología , Proteínas Proto-Oncogénicas c-bcl-6/genéticaRESUMEN
Neural stem cells (NSCs) persist in the dentate gyrus of the hippocampus into adulthood and are essential for both neurogenesis and neural circuit integration. Exosomes have also been shown to play vital roles in regulating biological processes of receptor cells as a medium for cell-to-cell communication signaling molecules. The precise molecular mechanisms of exosome-mediated signaling, however, remain largely unknown. Here, we found that exosomes produced by denervated hippocampi following fimbria-fornix transection could promote the differentiation of hippocampal neural precursor cells into cholinergic neurons in coculture with NSCs. Furthermore, we found that 14 circular RNAs (circRNAs) were upregulated in hippocampal exosomes after fimbria-fornix transection using high-throughput RNA-Seq technology. We further characterized the function and mechanism by which the upregulated circRNA Acbd6 (acyl-CoA-binding domain-containing 6) promoted the differentiation of NSCs into cholinergic neurons using RT-quantitative PCR, Western blot, ELISA, flow cytometry, immunohistochemistry, and immunofluorescence assay. By luciferase reporter assay, we demonstrated that circAcbd6 functioned as an endogenous miR-320-5p sponge to inhibit miR-320-5p activity, resulting in increased oxysterol-binding protein-related protein 2 expression with subsequent facilitation of NSC differentiation. Taken together, our results suggest that circAcbd6 promotes differentiation of NSCs into cholinergic neurons via miR-320-5p/oxysterol-binding protein-related protein 2 axis, which contribute important insights to our understanding of how circRNAs regulate neurogenesis.
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Diferenciación Celular , Neuronas Colinérgicas , MicroARNs , Células-Madre Neurales , ARN Circular , Receptores de Esteroides , Animales , Diferenciación Celular/genética , Neuronas Colinérgicas/citología , MicroARNs/genética , MicroARNs/metabolismo , Células-Madre Neurales/citología , ARN Circular/genética , ARN Circular/metabolismo , Ratas , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismoRESUMEN
OBJECTIVE: To explore the effect of the 2016 Chinese second child policy and different maternal ages on adverse perinatal outcomes. METHODS: Clinical data were collected from 22 monitoring hospitals in Hebei Province from January 1, 2013, to December 31, 2021. A total of 413,892 parturient were divided into 3 groups based on delivery age: 20-34, 35-39, and 40-55 years old. The clinical data were analyzed to explore the relationship among the 2016 Chinese second-child policy, maternal age, and various pregnancy risks. RESULTS: Pregnancy complications showed an upward trend from 2013 to 2021.The top 10 incidences of pregnancy complications in Hebei Province were anemia, small for gestational age (SGA), large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM), premature delivery, preeclampsia (PE), postpartum hemorrhage (PPH), placenta previa, and placental abruption. The two-child policy was implemented in 2016. The incidence of pregnancy complications, anemia, GDM, PE, placental abruption, cesarean delivery, premature delivery, SGA, LGA, macrosomia in 2016-2021 was significantly higher than that in 2013-2015 (P<0.05), and the proportion of women of advanced maternal age (AMA, ≥ 35 years old) increased from 2013 to 2021. Advanced maternal age was a risk factor for most assessed adverse pregnancy outcomes, including GDM, PE, placenta previa, placenta abruption, cesarean delivery, PPH, premature delivery, SGA, LGA and macrosomia. CONCLUSION: After the adjustment of the "second-child" policy, the incidence of pregnancy complications increased. Moreover, the risk of adverse pregnancy outcomes in AMA has increased. Early prevention and intervention should be implemented to cope with the occurrence of adverse perinatal outcomes.
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Política de Planificación Familiar , Edad Materna , Complicaciones del Embarazo , Resultado del Embarazo , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Desprendimiento Prematuro de la Placenta/epidemiología , China/epidemiología , Diabetes Gestacional/epidemiología , Pueblos del Este de Asia/estadística & datos numéricos , Macrosomía Fetal/epidemiología , Placenta Previa/epidemiología , Hemorragia Posparto/epidemiología , Preeclampsia/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Política de Planificación Familiar/tendencias , Factores de Edad , Persona de Mediana EdadRESUMEN
In the adult mammalian brain, neural stem cells (NSCs) are the precursor cells of neurons that contribute to nervous system development, regeneration, and repair. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cell fate determination and differentiation by negatively regulating gene expression. Here, we identified a post-transcriptional mechanism, centred around miR-130a-3p that regulated NSC differentiation. Importantly, overexpressing miR-130a-3p promoted NSC differentiation into neurons, whereas inhibiting miR-130a-3p function reduced the number of neurons. Then, the quantitative PCR, Western blot and dual-luciferase reporter assays showed that miR-130a-3p negatively regulated acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. Additionally, inhibition of Acsl4 promoted NSC differentiation into neurons, whereas silencing miR-130a-3p partially suppressed the neuronal differentiation induced by inhibiting Acsl4. Furthermore, overexpressing miR-130a-3p or inhibiting Acsl4 increased the levels of p-AKT, p-GSK-3ß and PI3K. In conclusion, our results suggested that miR-130a-3p targeted Acsl4 to promote neuronal differentiation of NSCs via regulating the Akt/PI3K pathway. These findings may help to develop strategies for stem cell-mediated treatment for central nervous system diseases.
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MicroARNs , Células-Madre Neurales , Animales , Diferenciación Celular/genética , Glucógeno Sintasa Quinasa 3 beta , Mamíferos/genética , Mamíferos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Sistema Nervioso/metabolismo , Células-Madre Neurales/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genéticaRESUMEN
Exosomes transfer signaling molecules such as proteins, lipids, and RNAs to facilitate cell-cell communication and play an important role in the stem cell microenvironment. In previous work, we demonstrated that rat fimbria-fornix transection (FFT) enhances neurogenesis from neural stem cells (NSCs) in the subgranular zone (SGZ). However, how neurogenesis is modulated after denervation remains unknown. Here, we investigated whether exosomes in a denervated hippocampal niche may affect neurogenesis. Using the FFT rat model, we extracted hippocampal exosomes and identified them using western blots, transmission electron microscopy (TEM), and nanoparticle size measurement. We also used RNA sequencing and bioinformatic analysis of exosomes to identify noncoding RNA expression profiles and neurogenesis-related miRNAs, respectively. RNA sequencing analysis demonstrated 9 upregulated and 15 downregulated miRNAs. miR-3559-3P and miR-6324 increased gradually after FFT. Thus, we investigated the function of miR-3559-3P and miR-6324 with NSC proliferation and differentiation assays. Transfection of miR-3559-3p and miR-6324 mimics inhibited the proliferation of NSCs and promoted the differentiation of NSCs into neurons, while miR-3559-3p and miR-6324 inhibitors promoted NSC proliferation and inhibited neuronal differentiation. Additionally, the exosome marker molecules CD9, CD63, and Alix were expressed in exosomes extracted from the hippocampal niche. Finally, TEM showed that exosomes were â¼100 nm in diameter and had a "saucer-like" bilayer membrane structure. Taken together, these findings suggest that differentially expressed exosomes and their related miRNAs in the denervated hippocampal niche can promote differentiation of NSCs into neurons.
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Exosomas/metabolismo , Hipocampo/fisiología , Células-Madre Neurales/citología , Neurogénesis , Animales , Femenino , Fórnix/cirugía , Hipocampo/citología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Glioma multiforme (GBM) is the most common malignant primary brain tumors. Despite the considerable advances in GBM treatment, it is still one of the most lethal forms of brain tumor. New clinical biomarkers and therapeutic targets are immediately required. MicroRNAs (miRNAs) are a class of small, evolutionarily conserved noncoding RNAs and have emerged as the key regulators of many cancers. Here in this study, we showed that miR-674-5p was probably an important regulator of glioma cell growth. After the transfection with miR-674-5p mimic or inhibitor, we found that the expression level of miR-674-5p was negatively related with cell proliferation and migration in C6 cells. Based on the prediction of the target genes of miR-674-5p on the website, we chose Cullin 4B (Cul4b), a gene upregulated in GBM, and proved that it was a target of miR-674-5p. In addition, we explored the role of miR-674-5p in glioma growth in vivo. Taken together, the present study indicated that miR-674-5p suppressed glioma cell proliferation and migration by targeting Cul4b.
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Neoplasias Encefálicas , Proteínas Cullin , Glioma , MicroARNs , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioma/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , RatasRESUMEN
Insoluble dietary fiber (IDF) is a nutritional component constituting the building block of plant cell walls. Our understanding of the role of IDF in plant-based foods has advanced dramatically in recent years. In this Review, we summarize research progress on the subtypes, structure, analysis, and extraction methods of IDF. The impact of different food processing methods on the properties of IDF is discussed. The role of gut microbiota in the health benefits of IDF is introduced. This review provides a better understanding of the chemical features and biological functions of IDF, which may promote the future application of IDF in functional food products. Further investigation of the mechanisms underlying the health benefits of IDF enables the development of effective strategies for the prevention and treatment of human diseases.
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MicroRNA-33-3p (miR-33-3p) has been widely investigated for its roles in lipid metabolism and mitochondrial function; however, there are few studies on miR-33-3p in the context of neurological diseases. In this study, we investigated the functional role of miR-33-3p in rat pheochromocytoma PC12 cells. A miR-33-3p mimic was transduced into PC12 cells, and its effects on proliferation, apoptosis, and differentiation were studied using the MTS assay, EdU labeling, flow cytometry, qRT-PCR, western blot, ELISA, and immunofluorescence. We found that miR-33-3p significantly suppressed PC12 cell proliferation, but had no effect on apoptosis. Furthermore, miR-33-3p promoted the differentiation of PC12 cells into Tuj1-positive and choline acetyltransferase-positive neuron-like cells. Mechanistically, miR-33-3p repressed the expression of Slc29a1 in PC12 cells. Importantly, knocking down Slc29a1 in PC12 cells inhibited proliferation and induced differentiation into neuron-like cells. In conclusion, this study showed that miR-33-3p regulated Slc29a1, which in turn controlled the proliferation and differentiation of PC12 cells. Thus, we hypothesize that the miR-33-3p/Slc29a1 axis could be a promising therapeutic target for recovering neurons and the cholinergic nervous system.
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Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , MicroARNs/metabolismo , Animales , Apoptosis/fisiología , Ciclo Celular/fisiología , Células HEK293 , Humanos , Células PC12 , RatasRESUMEN
To investigate the effect of CXCL12 on regeneration of radial glia like cells after traumatic brain injury (TBI). We randomly divided 48 rats into 4 groups: (1) the sham group, rats were performed craniotomy only, (2) the control group, saline were injected into the ipsilateral cortex after TBI, (3) the CXCL12 group, CXCL12 were injected, and (4) the CXCL12â¯+â¯AMD3100 group, a mixture of CXCL12 and AMD3100 were injected. Seven days after TBI, the brain tissues were subjected to immunofluorescence double-labeled staining of BrdU/Nestin, BLBP/Nestin, BLBP/Vimentin, BLBP/SOX2, BLBP/CXCR4, BLBP/DCX. Western Blot assay was used to measure the levels of Nestin, BLBP, and Vimentin. Compared with the control group, CXCL12 treatment significantly increased the number of cells stained with BrdU/Nestin, BLBP/Nestin, and BLBP/Vimentin around the injured cortex and corpus callosum areas. CXCL12â¯+â¯AMD3100 treatment significantly decreased the number of these cells compared with the CXCL12 treatment and control group. The protein levels of Nestin, BLBP, and Vimentin had the same change trends as those of the immunofluorescence staining. The BLBP/Vimentin positive cells presented with the astrocyte pattern around the injured cortex area but with the RGCs pattern around the injured corpus callosum area. The BLBP positive cells also expressed CXCR4 and SOX2. Altogether, CXCL12 promotes the proliferation of neural precursor cells after TBI by combing to its receptor, CXCR4. The proliferating neural precursor cells presents radial glial cell like cells. The RGCs-like cells can differentiate into immature neurons and promote the migration of immature neurons.
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Lesiones Traumáticas del Encéfalo/metabolismo , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/administración & dosificación , Células Ependimogliales/metabolismo , Neurogénesis/efectos de los fármacos , Receptores CXCR4/metabolismo , Animales , Astrocitos/metabolismo , Bencilaminas/administración & dosificación , Lesiones Traumáticas del Encéfalo/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Cuerpo Calloso/metabolismo , Cuerpo Calloso/patología , Ciclamas/administración & dosificación , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Proteína de Unión a los Ácidos Grasos 7/metabolismo , Técnica del Anticuerpo Fluorescente , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Nestina/metabolismo , Neuronas/metabolismo , Neuropéptidos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/antagonistas & inhibidores , Factores de Transcripción SOXB1/metabolismo , Vimentina/metabolismoRESUMEN
Amine-functionalized silicon nanoparticles (A-SiNPs) with intense green fluorescence and photostability are synthesized via a one-step, low-cost hydrothermal method under mild conditions using 3-aminopropyl triethoxysilane (APTES) as a silicon source and L-ascorbic acid (AA) as a reducing reagent. The amine-rich surface not only improves water dispersability and stability of the A-SiNPs but also offers a specific copper(II) ion (Cu2+) coordination capability. The as-prepared A-SiNPs can be directly employed for Cu2+ detection in "turn-off" mode, resulting from Cu2+ coordination-induced fluorescence quenching effect. Under optimal conditions, Cu2+ detection was accomplished with a linear range from 1 to 500 µM and a limit of detection (LOD) at 0.1 µM, which was much lower than the maximum level (~ 20 µM) of Cu2+ in drinking water permitted by the US Environmental Protection Agency (EPA). In addition, the A-SiNPs were successfully used to detect Cu2+ in spiked river water, demonstrating its good selectivity and potential application for analysis of surface water samples. Graphical abstract.
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Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p, and miR-210-3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.
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Anticonvulsivantes/farmacología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Células-Madre Neurales/metabolismo , Ácido Valproico/farmacología , Animales , Diferenciación Celular , Células Cultivadas , Femenino , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Neurogénesis , Ratas , Ratas Sprague-DawleyRESUMEN
A high-resolution colorimetric immunoassay platform has been developed based on enzyme-catalyzed multicolor generation and smartphone-assisted signal readout. The multi-color generation is accomplished in this system through the urease-catalyzed urea hydrolysis-induced color change of the pH indicator phenol red, from yellow to orange to red over pH 6.6 to 8.0. The color change is easily tailored by controlling the urease activity via the inhibitor silver ion (Ag+), the amount of which is in turn adjusted by alkaline phosphatase (ALP)-catalyzed ascorbic acid (AA) production. An ALP-linked colorimetric immunoassay is readily realized based on the above urease catalyzed multicolor generation system. Under optimal conditions, a limit of detection (LOD) of 1.73 ng mL-1 and a dynamic range from 0 to 18 ng mL-1 are achieved with rabbit IgG as a model analyte. A colored picture for each test is directly taken using a smartphone and then quantitatively analyzed with the free software ImageJ, eliminating the use of expensive and desktop equipment. The dose-dependent multicolor display is easier to distinguish with the naked eye for qualitative or semiquantitative detection over the traditional one-color system. The developed immunoassay scheme provides a promising platform for on-site testing or applications in resource-poor areas.
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Colorimetría , Inmunoensayo , Teléfono Inteligente , Fosfatasa Alcalina/química , Animales , Ácido Ascórbico/química , Límite de Detección , Conejos , Plata , Urea/química , Ureasa/químicaRESUMEN
BACKGROUND: The denervated hippocampus provides a proper microenvironment for the survival and neuronal differentiation of neural progenitors. While thousands of lncRNAs were identified, only a few lncRNAs that regulate neurogenesis in the hippocampus are reported. The present study aimed to perform microarray expression profiling to identify long noncoding RNAs (lncRNAs) that might participate in the hippocampal neurogenesis, and investigate the potential roles of identified lncRNAs in the hippocampal neurogenesis. RESULTS: In this study, the profiling suggested that 74 activated and 29 repressed (|log fold-change|>1.5) lncRNAs were differentially expressed between the denervated and the normal hippocampi. Furthermore, differentially expressed lncRNAs associated with neurogenesis were found. According to the tissue-specific expression profiles, and a novel lncRNA (lncRNA2393) was identified as a neural regulator in the hippocampus in this study. The expression of lncRNA2393 was activated in the denervated hippocampus. FISH showed lncRNA2393 specially existed in the subgranular zone of the dentate gyrus in the hippocampus and in the cytoplasm of neural stem cells (NSCs). The knockdown of lncRNA2393 depletes the EdU-positive NSCs. Besides, the increased expression of lncRNA2393 was found to be triggered by the change in the microenvironment. CONCLUSION: We concluded that expression changes of lncRNAs exists in the microenvironment of denervated hippocampus, of which promotes hippocampal neurogenesis. The identified lncRNA lncRNA2393 expressed in neural stem cells, located in the subgranular zone of the dentate gyrus, which can promote NSCs proliferation in vitro. Therefore, the question is exactly which part of the denervated hippocampus induced the expression of lncRNA2393. Further studies should aim to explore the exact molecular mechanism behind the expression of lncRNA2393 in the hippocampus, to lay the foundation for the clinical application of NSCs in treating diseases of the central nervous system.
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Hipocampo/metabolismo , Neurogénesis/genética , ARN Largo no Codificante/genética , Animales , Diferenciación Celular/genética , Proliferación Celular , Análisis por Conglomerados , Desnervación , Femenino , Perfilación de la Expresión Génica , Silenciador del Gen , Masculino , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Ratas , Reproducibilidad de los Resultados , TranscriptomaRESUMEN
Adult hippocampal neurogenesis is essential for learning and memory, and its dysfunction is involved in neurodegenerative diseases. However, the molecular mechanisms underlying adult hippocampal neurogenesis are still largely unknown. Our previous studies indicated that the transcription factor Brn4 was upregulated and promoted neuronal differentiation of neural stem cells (NSCs) in the surgically denervated hippocampus in rats. In this study, we use high-throughput RNA sequencing to explore the molecular mechanisms underlying the enhancement of adult hippocampal neurogenesis induced by lentivirus-mediated Brn4 overexpression in vivo. After 10 days of the lentivirus injection, we found that the expression levels of genes related to neuronal development and maturation were significantly increased and the expression levels of genes related to NSC maintenance were significantly decreased, indicating enhanced neurogenesis in the hippocampus after Brn4 overexpression. Through RNA sequencing, we found that 658 genes were differentially expressed in the Brn4-overexpressed hippocampi compared with GFP-overexpressed controls. Many of these differentially expressed genes are involved in NSC division and differentiation. By using quantitative real-time PCR, we validated the expression changes of three genes, including Ctbp2, Notch2, and Gli1, all of which are reported to play key roles in neuronal differentiation of NSCs. Importantly, the expression levels of Ctbp2 and Notch2 were also significantly changed in the hippocampus of Brn4 KO mice, which indicates that the expression levels of Ctbp2 and Notch2 may be directly regulated by Brn4. Our current study provides a solid foundation for further investigation and identifies Ctbp2 and Notch2 as possible downstream targets of Brn4. © 2017 Wiley Periodicals, Inc.
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Regulación de la Expresión Génica/fisiología , Hipocampo , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis/fisiología , Factores del Dominio POU/metabolismo , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Ratones , Ratones Noqueados , Ratas , Ratas Sprague-DawleyRESUMEN
To investigate the effect of CXCL12 on migration of neural precursor cells after traumatic brain injury (TBI). We randomly divided 48 rats into four groups: (1) the sham group, rats were performed craniotomy only, (2) the control group, saline were injected into the ipsilateral cortex after TBI, (3) the CXCL12 group, CXCL12 were injected into the ipsilateral cortex after TBI, and (4) the CXCL12 + AMD3100 group, CXCL12 and AMD3100 were mixed together and injected into the ipsilateral cortex after TBI. At 7 days after TBI, the brain tissues were subjected to immunofluorescent double-labeled staining with the antibodies of CXCR4/DCX, MMP-2/DCX, MMP-2/GFAP, MMP-2/NeuN. Western blot assay was used to measure the protein levels of MMP-2. Compared with the control group, the number of CXCR4/DCX and MMP-2 positive cells around the injured corpus callosum area were significantly increased in the CXCL12 treatment group. The area occupied by these cells expanded and the shape changed from chain distribution to radial. CXCL12 + AMD3100 treatment significantly decreased the number and distribution area of CXCR4/DCX and MMP-2 positive cells compared with the CXCL12 treatment and control group. The DCX positive cells could not form chain or radial distribution. The protein expressions of MMP-2 had the similar change trends as the results of immunofluorescent staining. MMP-2 could be secreted by DCX, GFAP and NeuN positive cells. CXCL12/CXCR4 axis can improve the migration of the neuroblasts along the corpus callosum by stimulating the MMP-2 secretion of different types of cells.
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Lesiones Traumáticas del Encéfalo/metabolismo , Movimiento Celular/fisiología , Quimiocina CXCL12/administración & dosificación , Cuerpo Calloso/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Receptores CXCR4/metabolismo , Animales , Bencilaminas , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/patología , Movimiento Celular/efectos de los fármacos , Cuerpo Calloso/efectos de los fármacos , Cuerpo Calloso/patología , Ciclamas , Proteína Doblecortina , Compuestos Heterocíclicos/administración & dosificación , Inyecciones Intraventriculares , Masculino , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/antagonistas & inhibidoresRESUMEN
Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries.
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Movimiento Celular , Quimiocina CXCL12/metabolismo , Células Ependimogliales/metabolismo , Hipocampo/citología , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Animales , Quimiocina CXCL12/genética , Regulación hacia Abajo , Femenino , Fluorescencia , Fórnix/lesiones , Fórnix/metabolismo , Fórnix/patología , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Regulación hacia ArribaRESUMEN
The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation.
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Hipoxia-Isquemia Encefálica/terapia , Trasplante de Células Madre Mesenquimatosas , Neuronas/citología , Cordón Umbilical/citología , Animales , Diferenciación Celular/fisiología , Humanos , Hipoxia-Isquemia Encefálica/fisiopatología , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
CXCL12 and its physiologic receptor CXCR4 are involved in controlling cell survival, proliferation and migration in adult tissues. This study aimed to investigate the effects of CXCL12 on cortical neuron apoptosis in rats after traumatic brain injury (TBI) and the potential mechanisms involved. At 3 days after TBI, in situ terminal transferase d-UTP nick-end labeling assay (TUNEL) showed that the apoptotic index (AI) deceased significantly in the CXCL12 treatment group compared with the control group (p < 0.05). Immunofluorescence double-labeled staining revealed that most of the TUNEL positive cells were NeuN positive neurons. The change trends of active caspase-3 expression were similar as those of the AI. The Bcl-2:Bax ratio was upregulated in the CXCL12 group compared with the control group. However, the effect of CXCL12 could be partially reverted by the additional use of AMD3100 (a kind of antagonist of CXCR4) (p < 0.05). Our results indicated that after TBI in rats CXCL12 combing CXCR4 receptors could inhibit the caspase-3 pathway by upregulating Bcl-2:Bax ratio, which protect neurons from apoptosis.
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Apoptosis , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Corteza Cerebral/citología , Quimiocina CXCL12/metabolismo , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Apoptosis/efectos de los fármacos , Bencilaminas , Caspasa 3/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Ciclamas , Compuestos Heterocíclicos/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/metabolismo , Ratas , Receptores CXCR4/antagonistas & inhibidores , Regulación hacia ArribaRESUMEN
Consumer acceptance of Keitt mangoes (Mangifera indica L.) is significantly affected by their slow postharvest ripening. This work used gaseous chlorine dioxide (ClO2(g)) to prepare the ready-to-eat Keitt mango and explored the potential mechanisms for the mango ripening. Harvested mangoes were treated with 20 mg·L-1 of ClO2(g) or ethephon for 3 h (25 °C) and left in a climatic chamber with a temperature of 25 ± 1 °C and a relative humidity of 85 ± 5% for 4 d. The results showed that ClO2(g) treatment significantly promoted the orange coloration of mango flesh compared to the untreated control group. Moreover, ClO2(g) treatment significantly elevated the total soluble solids, total soluble sugar, and total carotenoids content of mangoes, whereas the firmness and titratable acidity were reduced. ClO2(g)-treated mangoes reached the edible window on day 2, as did mangoes treated with ethephon at the same concentration, except that the sweetness was prominent. The residual ClO2 level of the mangoes was <0.3 mg/kg during the whole storage time, which is a safe level for fruit. In addition, ClO2(g) significantly advanced the onset of ethylene peaks by 0.5 days and increased its production between days 0.5 and 2 compared to the control group. Consistently, the genes involved in ethylene biosynthesis including miACS6, miACO1, and miACO were upregulated. In sum, ClO2(g) can be a potential technique to reduce the time for harvested mango to reach the edible window, and it functions in modulating postharvest ripening by inducing ethylene biosynthesis.
RESUMEN
Gestational diabetes mellitus (GDM) is an unique metabolic disorder that occurs during pregnancy. Both GDM and advanced age increase the risk of adverse pregnancy outcomes. This study used a GDM cohort study to investigate the role of age in the adverse pregnancy outcomes for pregnant women with GDM. From 2015 to 2021, 308,175 pregnant women were selected, and the data received from 22 hospitals by the Hebei Province Maternal Near Miss Surveillance System. There were 24,551 pregnant women with GDM that were divided into five groups by age (20-24, 25-29, 30-34, 35-39, 40-44 years old). Because the prevalence of adverse pregnancy outcomes was lower in pregnant women with GDM aged 25-29, they were used as a reference group (P < 0.05). Compared with GDM women aged 25-29 years, GDM women aged 35-44 years had a significant higher risk of cesarean delivery (aOR: 2.86, 95% CI 2.52-3.25) (P < 0.001), abnormal fetal position (aOR: 1.78, 95% CI 1.31-2.37) (P < 0.001), pre-eclampsia (aOR: 1.28, 95% CI 1.01-1.61) (P < 0.05), macrosomia (aOR: 1.25, 95% CI 1.08-1.45) (P < 0.05), and large for gestational age (LGA) (aOR: 1.16, 95% CI 1.02-1.31) (P < 0.05), GDM women aged 40-44 years had a higher risk of placenta previa (aOR: 2.53, 95% CI 1.01-6.35) (P < 0.05), anemia (aOR: 3.45, 95% CI 1.23-9.68) (P < 0.05) and small for gestational age (aOR: 1.32, 95% CI 1.01-1.60) (P < 0.05). Advanced maternal age was an independent risk factor for abnormal fetal position, pre-eclampsia, anemia, macrosomia, and LGA in pregnant women with GDM.