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1.
Cell Commun Signal ; 22(1): 155, 2024 02 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424563

RESUMEN

BACKGROUND: Vascular endothelial cells are pivotal in the pathophysiological progression following spinal cord injury (SCI). The UTX (Ubiquitously Transcribed Tetratripeptide Repeat on Chromosome X) serves as a significant regulator of endothelial cell phenotype. The manipulation of endogenous neural stem cells (NSCs) offers a compelling strategy for the amelioration of SCI. METHODS: Two mouse models were used to investigate SCI: NSCs lineage-traced mice and mice with conditional UTX knockout (UTX KO) in endothelial cells. To study the effects of UTX KO on neural differentiation, we harvested extracellular vesicles (EVs) from both UTX KO spinal cord microvascular endothelial cells (SCMECs) and negative control SCMECs. These EVs were then employed to modulate the differentiation trajectory of endogenous NSCs in the SCI model. RESULTS: In our NSCs lineage-traced mice model of SCI, a marked decrease in neurogenesis was observed post-injury. Notably, NSCs in UTX KO SCMECs mice showed enhanced neuronal differentiation compared to controls. RNA sequencing and western blot analyses revealed an upregulation of L1 cell adhesion molecule (L1CAM), a gene associated with neurogenesis, in UTX KO SCMECs and their secreted EVs. This aligns with the observed promotion of neurogenesis in UTX KO conditions. In vivo administration of L1CAM-rich EVs from UTX KO SCMECs (KO EVs) to the mice significantly enhanced neural differentiation. Similarly, in vitro exposure of NSCs to KO EVs resulted in increased activation of the Akt signaling pathway, further promoting neural differentiation. Conversely, inhibiting Akt phosphorylation or knocking down L1CAM negated the beneficial effects of KO EVs on NSC neuronal differentiation. CONCLUSIONS: In conclusion, our findings substantiate that EVs derived from UTX KO SCMECs can act as facilitators of neural differentiation following SCI. This study not only elucidates a novel mechanism but also opens new horizons for therapeutic interventions in the treatment of SCI. Video Abstract.


Asunto(s)
Vesículas Extracelulares , Molécula L1 de Adhesión de Célula Nerviosa , Células-Madre Neurales , Traumatismos de la Médula Espinal , Animales , Ratones , Diferenciación Celular , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Vesículas Extracelulares/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/farmacología , Células-Madre Neurales/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia
2.
BMC Infect Dis ; 24(1): 794, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112970

RESUMEN

BACKGROUND: COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children. METHODS: This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection. RESULTS: Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29-0.31, P < 0.05). CONCLUSIONS: In children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Desensibilización Inmunológica , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/inmunología , Niño , Estudios Retrospectivos , Masculino , Femenino , Preescolar , SARS-CoV-2/inmunología , Inyecciones Subcutáneas , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/métodos , Adolescente , Animales , Pyroglyphidae/inmunología , Alérgenos/inmunología , Alérgenos/efectos adversos , Alérgenos/administración & dosificación , Lactante
3.
J Neuroinflammation ; 20(1): 259, 2023 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951955

RESUMEN

Spinal cord injury (SCI) can prompt an immediate disruption to the blood-spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI.


Asunto(s)
Cadenas Ligeras de Miosina , Traumatismos de la Médula Espinal , Animales , Ratones , Ratas , Barrera Hematoencefálica/metabolismo , Células Endoteliales/metabolismo , Histona Demetilasas/genética , Cadenas Ligeras de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Permeabilidad , Fosforilación , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismo
4.
Mar Drugs ; 22(1)2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38248640

RESUMEN

Chemical epigenetic cultivation of the sponge-derived fungus Pestalotiopsis sp. SWMU-WZ04-1 contributed to the identification of twelve polyketide derivatives, including six new pestalotiopols E-J (1-6) and six known analogues (7-12). Their gross structures were deduced from 1D/2D NMR and HRESIMS spectroscopic data, and their absolute configurations were further established by circular dichroism (CD) Cotton effects and the modified Mosher's method. In the bioassay, the cytotoxic and antibacterial activities of all compounds were evaluated. Chlorinated benzophenone derivatives 7 and 8 exhibited inhibitory effects on Staphylococcus aureus and Bacillus subtilis, with MIC values varying from 3.0 to 50 µg/mL. In addition, these two compounds were cytotoxic to four types of human cancer cells, with IC50 values of 16.2~83.6 µM. The result showed that compound 7 had the probability of being developed into a lead drug with antibacterial ability.


Asunto(s)
Pestalotiopsis , Policétidos , Humanos , Antibacterianos/farmacología , Bacillus subtilis , Hongos , Policétidos/farmacología
5.
J Anat ; 240(2): 268-278, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34622448

RESUMEN

The structure of spinal motion segments and spinal vasculature is complicated. Visualizing the three-dimensional (3D) structure of the spine may provide guidance for spine surgery. However, conventional imaging techniques fail to simultaneously obtain 3D images of soft and hard tissues, and achieving such coimaging states of the spine and its vascular networks remains a challenge. Synchrotron radiation micro-CT (SRµCT) provides a relatively effective and novel method of acquiring detailed 3D information. In this study, specimens of the thoracic spine were obtained from six mice. SRµCT was employed to acquire 3D images of the structure, and histologic staining was performed for comparisons with the SRµCT images. The whole spinal motion segments and the spinal vascular network were simultaneously explored at high resolution. The mean thickness of the cartilaginous end plates (CEPs) and the volume of the intervertebral discs (IVDs) were calculated. The surface of the CEPs and the facet joint cartilage (FJC) were presented as heat maps, which allowed for direct visualization of the thickness distribution. Regional division revealed heterogeneity among the ventral, central, and dorsal parts of the CEPs and between the superior and inferior parts of the facet processes. Moreover, the connections and spatial morphology of the spinal vascular network were visualized. Our study indicates that SRµCT imaging is an ideal method for high-resolution visualization and 3D morphometric analysis of the whole spinal motion segments and spinal vascular network.


Asunto(s)
Disco Intervertebral , Articulación Cigapofisaria , Animales , Imagenología Tridimensional/métodos , Ratones , Sincrotrones , Microtomografía por Rayos X/métodos
6.
Mol Biol Rep ; 49(6): 5585-5593, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35543829

RESUMEN

BACKGROUND: Semiliquidambar cathayensis is a traditional medicinal plant and endemic species in China. Its roots, branches, leaves, bark, and nectar are known to have therapeutic effects against rheumatoid arthritis, lumbar muscle strain, and several other diseases. However, limited knowledge regarding the molecular properties of S. cathayensis highlights the need for further research in order to elucidate the underlying pathways governing the synthesis of its active ingredients and regulation of its accumulation processes. METHODS: We conducted transcriptome sequencing of the leaf, stem and root epidermises, and stem and root xylems of S. cathayensis with three biological replicates. Moreover, candidate genes involved in terpenoid biosynthesis, such as IDI, FPPS, DXR, SQS, GPPS, and HMGR were selected for quantitative real-time PCR analysis. RESULTS: We identified 88,582 unigenes. Among which, 36,144 unigenes were annotated to the nr protein database, 21,981 to the Gene Ontology database, 11,565 to the Clusters of Orthologous Groups database, 24,209 to the Pfam database, 21,685 to the SWISS-PROT database, and 12,753 to the Kyoto Encyclopedia of Genes and Genomes (KEGG), with 5072 unigenes common to all six databases. Of those annotated using the KEGG database, 187 unigenes were related to the terpenoid metabolism pathway, and expression analysis of the related genes indicated that the mevalonate and methylerythritol 4-phosphate pathways play different roles in terpenoid biosynthesis in different tissues of S. cathayensis. CONCLUSIONS: These findings greatly expand gene resources of S. cathayensis and provide basic data for the study of the biosynthetic pathways and molecular mechanisms of terpenoids.


Asunto(s)
Hamamelidaceae , Transcriptoma , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Hamamelidaceae/genética , Anotación de Secuencia Molecular , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Terpenos/metabolismo , Transcriptoma/genética
7.
BMC Pregnancy Childbirth ; 22(1): 412, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35578202

RESUMEN

OBJECTIVE: To understand the use of online antenatal education classes accessed via the Mother and Child Health Handbook app during the COVID-19 pandemic in order to provide a basis and suggestions for optimizing Internet education during pregnancy under public health emergencies. METHODS: We compared and analyzed the use of online antenatal education classes via the Mother and Child Health Handbook app in Hangzhou in 2019 and 2020 (during the COVID-19 pandemic). RESULTS: Between January 1, 2019, and December 31, 2020, a total of 229,794 pregnant women created files and registered for the app, including 124,273 women in 2019 and 105,521 women in 2020. More pregnant women participated in online antenatal education learning (n = 36,379/34.5% vs. 29,226/23.5%, p = 0.000) in 2020 than in 2019. The proportion of pregnant women in the 18-34-year-old group who participated in online learning was higher than that in the advanced age group, and the difference was statistically significant (2019: 24.3% vs. 18.8%, p = 0.000) (2020: 35.7% vs. 27.4%, p = 0.000). More pregnant women accessed online antenatal education during early pregnancy (n = 13,463/37.0% vs. 9088/31.1%, p = 0.000) in 2020 than in 2019. Similar percentages of pregnant women participated in online antenatal education during mid-pregnancy (n = 15,426/52.8% vs. 19,269/53.0%, p = 0.639) in 2019 and 2020. Fewer pregnant women accessed online antenatal education during late pregnancy (n = 10,246/28.2% vs. 9476/32.4%, p = 0.000) in 2020 than in 2019. Fewer pregnant women choose to take 'Puerperal Health' courses in 2020 than in 2019 (early pregnancy: 36.20% vs. 42.79%, p = 0.000; mid-pregnancy: 41.65% vs. 48.19%, p = 0.000; late pregnancy: 55.31% vs. 58.41%, p = 0.000). Fewer pregnant women choose to take 'Psychological Adjustment' courses in 2020 than in 2019 (early pregnancy: 21.59% vs. 29.60%, p = 0.000; mid-pregnancy: 26.20% vs. 40.50%, p = 0.000; late pregnancy: 12.79% vs. 42.53%, p = 0.000). More pregnant women choose to study 'Nutrition and Exercise' in 2020 than in 2019 (early pregnancy: 44.48% vs. 25.95%, p = 0.000; mid-pregnancy: 47.77% vs. 40.75%, p = 0.000; late pregnancy: 55.94% vs. 42.99%, p = 0.000). "Pregnancy Care and Fetal Development" was the most selected course by pregnant women in early pregnancy (2019: 67.50%; 2020: 71.39%) and middle pregnancy (2019: 67.01%; 2020: 82.05%), and the proportion in 2020 was higher than it was in 2019. "Baby care" was the most selected course by pregnant women in late pregnancy, and the proportion in 2020 was higher than it was in 2019 (78.31% vs. 72.85%). CONCLUSION: During the COVID-19 pandemic, online antenatal education was well-used by pregnant women. More women participated in the online antenatal education modules during the COVID-19 pandemic than during 2019.The proportion of choosing different courses for pregnant women before and after the COVID-19 epidemic varied, and the learning course needs of pregnant women in different trimesters were different.


Asunto(s)
COVID-19 , Educación a Distancia , Aplicaciones Móviles , Educación Prenatal , Adolescente , Adulto , Niño , Femenino , Humanos , Pandemias , Embarazo , Mujeres Embarazadas/psicología , Atención Prenatal , Adulto Joven
8.
Mar Drugs ; 20(11)2022 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-36421989

RESUMEN

Five undescribed polyketide derivatives, pestaloketides A-E (1-5), along with eleven known analogues (6-16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 µM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 µM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads.


Asunto(s)
Policétidos , Humanos , Policétidos/farmacología , Pestalotiopsis , Simulación del Acoplamiento Molecular , Hongos , Antiinflamatorios/farmacología
9.
BMC Musculoskelet Disord ; 23(1): 619, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35761205

RESUMEN

STUDY DESIGN: This is a retrospective study. BACKGROUND: To assess and compare the clinical outcomes of posterior unilateral limited laminectomy (ULL) or bilateral laminectomy (BL) debridement and bone grafting fusion combined with internal fixation among aged patients with single-segment thoracic and lumbar tuberculosis (SST/LTB). MATERIALS AND METHODS: We performed a retrospective study on aged patients (age > 65 years old) with SST/LTB from January 2010 to October 2018. We reviewed 36 aged patients who were treated with BL and 31 aged patients treated with ULL. All participants had undergone and finished a three-year follow-up. The outcomes were evaluated by the improvement of neurological function, correction Cobb angle, bone fusion time, and back pain, as well as operative time, blood loss, hospital stay, and postoperative complications. RESULTS: The operative time, blood loss volume, and incidence of complications in group B were significantly less than those in group A (P < 0.01). The postoperative kyphotic angle in both groups was reduced significantly compared to the preoperative status (P < 0.01). The percentage of neurological improvement was 92.9% in group A and 90.9% in group B. All patients achieved solid bone fusion after surgery. At three-year follow-up, the angle loss in group B was significantly less than that in group A (P < 0.01); Furthermore, patients in group B had a lower average visual analog scale score of back pain and Oswestry Disability Index score than patients in group A (P < 0.05). CONCLUSIONS: For aged patients with SST/LTB, ULL is a safer and more effective surgical treatment than BL.


Asunto(s)
Desbridamiento , Laminectomía , Fusión Vertebral , Tuberculosis de la Columna Vertebral , Anciano , Trasplante Óseo , Desbridamiento/efectos adversos , Desbridamiento/métodos , Humanos , Laminectomía/efectos adversos , Laminectomía/métodos , Vértebras Lumbares/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Tuberculosis de la Columna Vertebral/cirugía
10.
Acta Neurochir (Wien) ; 164(10): 2637-2644, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36070003

RESUMEN

BACKGROUND: Posterior limited unilateral fenestration approach is extensively used in the treatment of many spinal diseases. But whether it is suitable for spinal tuberculosis (TB) is rarely reported. Hence, the current study evaluated the feasibility and efficacy of the posterior limited unilateral fenestration (PLUF) debridement, bone grafting fusion, and instrumentation to treat single-segment thoracic and lumbar TB. METHODS: Eighty-three patients (45 male and 38 female) aged 17-79 years old with the single-segment thoracic and lumbar TB who underwent PLUF debridement, bone grafting fusion, and instrumentation from our hospital were recruited for this study. The operation time, blood loss volume, postoperative complication rate, kyphotic Cobb angle, neurological functional improvement defined by the American Spinal Injury Association (ASIA) classification, the visual analogue scale (VAS) score, and the bone fusion time were utilized for assessing the clinical feasibility and efficacy. RESULTS: The average follow-up time was 46.9 ± 13.1 (24-72) months. At the last follow-up, the mean kyphotic Cobb angle was significantly reduced from preoperative 23.0° ± 15.3° to postoperative 8.3° ± 11.0° (p < 0.001). Based on the ASIA classification, 89.2% (33 out of 37) patients with preoperative neurological impairment indicated good neurological improvement after the surgery. The VAS pain score significantly decreased from preoperative 6.9 ± 1.1 to 1.3 ± 0.7 3 months after operation (p < 0.001). All the patients achieved solid bony fusion within 13 months of surgery. CONCLUSIONS: For patients with single-segment thoracic and lumbar TB, PLUF debridement, bone grafting fusion, and instrumentation are a feasible and effective surgical treatment.


Asunto(s)
Cifosis , Fusión Vertebral , Tuberculosis de la Columna Vertebral , Adolescente , Adulto , Anciano , Trasplante Óseo/efectos adversos , Desbridamiento/efectos adversos , Femenino , Humanos , Cifosis/etiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/cirugía , Adulto Joven
11.
Nano Lett ; 21(16): 7070-7078, 2021 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-34100613

RESUMEN

Using a three-dimensional (3D) Li-ion conducting ceramic network, such as Li7La3Zr2O12 (LLZO) garnet-type oxide conductor, has proved to be a promising strategy to form continuous Li ion transfer paths in a polymer-based composite. However, the 3D network produced by brittle ceramic conductor nanofibers fails to provide sufficient mechanical adaptability. In this manuscript, we reported a new 3D ion-conducting network, which is synthesized from highly loaded LLZO nanoparticles reinforced conducting polymer nanofibers, by creating a lightweight continuous and interconnected LLZO-enhanced 3D network to outperform conducting heavy and brittle ceramic nanofibers to offer a new design principle of composite electrolyte membrane featuring all-round properties in mechanical robustness, structural flexibility, high ionic conductivity, lightweight, and high surface area. This composite-nanofiber design overcomes the issues of using ceramic-only nanoparticles, nanowires, or nanofibers in polymer composite electrolyte, and our work can be considered as a new generation of composite electrolyte membrane in composite electrolyte development.

12.
Histochem Cell Biol ; 155(4): 477-489, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33398435

RESUMEN

Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRµCT) and the Golgi-cox staining were used. We optimized the Golgi-Cox method (GCM) and developed a modified GCM (M-GCM), which improved background staining, reduced the number of artefacts, and diminished the impact of incomplete vasculature compared to the current GCM. Moreover, we achieved high-resolution 3D imaging of the detailed neuronal network in the spinal cord through the combination of SRµCT and M-GCM. Our results showed that the M-GCM increased the contrast between the neuronal structure and its surrounding extracellular matrix. Compared to the GCM, the M-GCM also diminished the impact of the artefacts and incomplete vasculature on the 3D image. Additionally, the 3D neuronal architecture was successfully quantified using a combination of SRµCT and M-GCM. The SRµCT was shown to be a valuable non-destructive tool for 3D visualization of the neuronal network in the broad 3D region of the spinal cord. Such a combinatorial method will, therefore, transform the presentation of Golgi staining from 2 to 3D, providing significant improvements in the 3D rendering of the neuronal network.


Asunto(s)
Aparato de Golgi/química , Imagenología Tridimensional , Neuronas/citología , Médula Espinal/citología , Coloración y Etiquetado , Microtomografía por Rayos X , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Sincrotrones
13.
PLoS Biol ; 16(6): e2004880, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29879109

RESUMEN

N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here, we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout (cKO) mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion-induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.


Asunto(s)
Adenosina/análogos & derivados , Cerebelo/embriología , Metiltransferasas/metabolismo , ARN Mensajero/genética , Adenosina/metabolismo , Empalme Alternativo/genética , Animales , Apoptosis/genética , Células Cultivadas , Cerebelo/anomalías , Cerebelo/patología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Regulación de la Expresión Génica/genética , Metilación , Metiltransferasas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/patología , Estabilidad del ARN/genética , ARN Mensajero/metabolismo
14.
Mol Ther ; 27(12): 2134-2146, 2019 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-31495776

RESUMEN

The regeneration of the blood vessel system post spinal cord injury (SCI) is essential for the repair of neurological function. As a significant means to regulate gene expression, epigenetic regulation of angiogenesis in SCI is still largely unknown. Here, we found that Ubiquitously Transcribed tetratricopeptide repeat on chromosome X (UTX), the histone H3K27 demethylase, increased significantly in endothelial cells post SCI. Knockdown of UTX can promote the migration and tube formation of endothelial cells. The specific knockout of UTX in endothelial cells enhanced angiogenesis post SCI accompanied with improved neurological function. In addition, we found regulation of UTX expression can change the level of microRNA 24 (miR-24) in vitro. The physical binding of UTX to the promotor of miR-24 was indicated by chromatin immunoprecipitation (ChIP) assay. Meanwhile, methylation sequencing of endothelial cells demonstrated that UTX could significantly decrease the level of methylation in the miR-24 promotor. Furthermore, miR-24 significantly abolished the promoting effect of UTX deletion on angiogenesis in vitro and in vivo. Finally, we predicted the potential target mRNAs of miR-24 related to angiogenesis. We indicate that UTX deletion can epigenetically promote the vascular regeneration and functional recovery post SCI by forming a regulatory network with miR-24.


Asunto(s)
Células Endoteliales/citología , Epigénesis Genética , Eliminación de Gen , Histona Demetilasas/fisiología , Regeneración , Traumatismos de la Médula Espinal/terapia , Animales , Movimiento Celular , Proliferación Celular , Metilación de ADN , Células Endoteliales/fisiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/genética , Regiones Promotoras Genéticas , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patología
15.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31434093

RESUMEN

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Asunto(s)
Silenciador del Gen , Antígenos de Histocompatibilidad/genética , N-Metiltransferasa de Histona-Lisina/deficiencia , N-Metiltransferasa de Histona-Lisina/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/prevención & control , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patología , Apoptosis/genética , Cadherinas/biosíntesis , Adhesión Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/prevención & control , Neoplasias del Cuello Uterino/genética
16.
J Synchrotron Radiat ; 26(Pt 3): 607-618, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-31074423

RESUMEN

There has been increasing interest in using high-resolution micro-tomography to investigate the morphology of neurovascular networks in the central nervous system, which remain difficult to characterize due to their microscopic size as well as their delicate and complex 3D structure. Synchrotron radiation X-ray imaging, which has emerged as a cutting-edge imaging technology with a high spatial resolution, provides a novel platform for the non-destructive imaging of microvasculature networks at a sub-micrometre scale. When coupled with computed tomography, this technique allows the characterization of the 3D morphology of vasculature. The current review focuses on recent progress in developing synchrotron radiation methodology and its application in probing neurovascular networks, especially the pathological changes associated with vascular abnormalities in various model systems. Furthermore, this tool represents a powerful imaging modality that improves our understanding of the complex biological interactions between vascular function and neuronal activity in both physiological and pathological states.


Asunto(s)
Sistema Nervioso Central/irrigación sanguínea , Microvasos/diagnóstico por imagen , Sincrotrones , Microtomografía por Rayos X/métodos , Animales , Humanos
17.
Reprod Fertil Dev ; 31(2): 366-376, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30253120

RESUMEN

Fetal bovine serum (FBS) supplementation has beneficial effects on invitro porcine embryonic development, but the underlying mechanisms are unclear. In the present study we found that the addition of FBS to PZM-3 increased the number of cells in porcine blastocysts and hatching rate invitro primarily by promoting proliferation of the inner cell mass and further differentiation. Moreover, based on the following results, we surmise that FBS benefits blastocyst development by activating Rho-associated kinase (ROCK) signalling: (1) the ROCK signalling inhibitor Y-27632 decreased the blastocyst rate and the number of cells in blastocysts, whereas FBS rescued the developmental failure induced by Y-27632; (2) the mRNA levels of two ROCK isoforms, ROCK1 and ROCK2, were significantly increased in blastocysts derived from medium containing FBS; and (3) FBS increased RhoA/Rho-kinase expression in the nucleus of embryonic cells. These results indicate that FBS promotes the invitro development of porcine embryos by activating ROCK signalling in a chemically defined medium.


Asunto(s)
Blastocisto/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Suero , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Amidas/farmacología , Animales , Blastocisto/metabolismo , Medios de Cultivo , Técnicas de Cultivo de Embriones , Desarrollo Embrionario/fisiología , Femenino , Piridinas/farmacología , Transducción de Señal/fisiología , Porcinos
18.
J Synchrotron Radiat ; 24(Pt 2): 482-489, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28244444

RESUMEN

The spinal cord is the primary neurological link between the brain and other parts of the body, but unlike those of the brain, advances in spinal cord imaging have been challenged by the more complicated and inhomogeneous anatomy of the spine. Fortunately with the advancement of high technology, phase-contrast synchrotron radiation microtomography has become widespread in scientific research because of its ability to generate high-quality and high-resolution images. In this study, this method has been employed for nondestructive imaging of the internal microstructure of rat spinal cord. Furthermore, digital virtual slices based on phase-contrast synchrotron radiation were compared with conventional histological sections. The three-dimensional internal microstructure of the intramedullary arteries and nerve fibers was vividly detected within the same spinal cord specimen without the application of a stain or contrast agent or sectioning. With the aid of image post-processing, an optimization of vessel and nerve fiber images was obtained. The findings indicated that phase-contrast synchrotron radiation microtomography is unique in the field of three-dimensional imaging and sets novel standards for pathophysiological investigations in various neurovascular diseases.


Asunto(s)
Microvasos , Fibras Nerviosas , Médula Espinal/diagnóstico por imagen , Animales , Imagenología Tridimensional , Microscopía de Contraste de Fase , Microvasos/diagnóstico por imagen , Ratas , Médula Espinal/irrigación sanguínea , Sincrotrones , Microtomografía por Rayos X
19.
BMC Musculoskelet Disord ; 18(1): 504, 2017 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-29187182

RESUMEN

BACKGROUND: Sacroiliac joint tuberculosis(SJT) is relatively uncommon, but it may cause severe sacroiliac joint destruction and functional disorder. Few studies in the literature have been presented on SJT, reports of surgical treatment for SJT are even fewer. In this study, we retrospectively reviewed surgical management of patients with severe SJT of 3 different types and proposed to reveal the clinical manifestations and features and aim to determine the efficiency and security of such surgical treatment. METHODS: We reviewed 17 patients with severe SJT of 3 different types who underwent posterior open-window focal debridement and bone graft for joint fusion. Among them,five patients with anterior sacral abscess had anterior abscess curettage before debridement. Two patients with lumbar vertebral tuberculosis received one-stage posterior tuberculous debridement, interbody fusion and instrumentation. Follow-up was performed 36 months (26 to 45 months) using the following parameters: erythrocyte sedimentation rate(ESR), status of joint bony fusion on CT scan, visual analogue scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: Buttock pain and low back pain were progressively relieved with time. 6 months later, pain was not obvious, and ESR resumed to normal levels within 3 months. Solid fusion of the sacroiliac joint occurred within 12 months in all cases. No complications or recurrence occurred. At final follow-up, all patients had no pain or only minimal discomfort over the affected joint and almost complete functional recovery. CONCLUSIONS: Posterior open-window focal debridement and joint fusion is an efficient and secure surgical method to treat severe SJT. If there is an abscess in the front of the sacroiliac joint, anterior abscess curettage should be performed as a supplement.


Asunto(s)
Absceso/cirugía , Desbridamiento/métodos , Dolor/cirugía , Articulación Sacroiliaca/cirugía , Fusión Vertebral , Tuberculosis de la Columna Vertebral/cirugía , Absceso/complicaciones , Absceso/diagnóstico por imagen , Absceso/microbiología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/microbiología , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Mycobacterium/aislamiento & purificación , Dolor/etiología , Dimensión del Dolor , Estudios Retrospectivos , Articulación Sacroiliaca/diagnóstico por imagen , Articulación Sacroiliaca/microbiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Tuberculosis de la Columna Vertebral/complicaciones , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/microbiología , Adulto Joven
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(12): 1345-51, 2015 Dec.
Artículo en Zh | MEDLINE | ID: mdl-26739077

RESUMEN

OBJECTIVE: To investigate the clinical efficacy and feasibility of surgical treatment for thoracic spinal tuberculosis with intraspinal abscesses by internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion via a posterior only approach.
 METHODS: A total of 37 pantients (24 males and 13 females) with thoracic spinal tuberculosis complicated with intraspinal abscess lesions were admitted to our hospital, with age 13-68(39.7 ± 9.1) years old. Spinal lesions of segmental kyphosis Cobb angle was 8°-62° (29.6° ± 3.6°). Frankel grade system was used to assess neurological function. According to the system, there were 3, 7, 19 and 8 cases for grade B, C, D and E, respectively. All 37 cases were treated with internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion via a posterior only approach.
 RESULTS: The mean duration for follow-up was 24-90 (53.0 ± 15.7) months. Intraoperative dural tear occurred in 1 cases with cerebrospinal fluid leakage after operation; 2 cases showed postoperative neurological complications; delayed wound healing occurred in 2 cases. The postoperative kyphotic angle was 5°-21° (8.3° ± 1.3°). The kyphotic angle was 8°-26° (10.1° ± 1.9°) at the last follow-up. By the time of the last follow-up, all patients with preoperative neurological symptoms improved at different degree. According to Frankel classification, 2 cases recovered from grade B to D, 1 case from grade B to E, 3 cases from grade C to D, 4 cases from grade C to E, 13 cases from grade D to E. No failure in fixation and pseudarthrosis. All patients obtained satisfactory bone graft fusion.
 CONCLUSION: Posterior internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion might be a effective and feasible method for treatment of thoracic spinal tuberculosis with intraspinal abscess lesions.


Asunto(s)
Absceso/cirugía , Descompresión Quirúrgica , Tuberculosis de la Columna Vertebral/cirugía , Absceso/patología , Adolescente , Adulto , Anciano , Trasplante Óseo , Niño , Desbridamiento , Femenino , Fijación Interna de Fracturas , Humanos , Cifosis/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Fusión Vertebral , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Tuberculosis de la Columna Vertebral/patología , Adulto Joven
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