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1.
J Neurosci ; 43(44): 7351-7360, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37684030

RESUMEN

Bilateral common carotid artery (CCA) stenosis (BCAS) is a useful model to mimic vascular cognitive impairment and dementia (VCID). However, current BCAS models have the disadvantages of high cost and incompatibility with magnetic resonance imaging (MRI) scanning because of metal implantation. We have established a new low-cost VCID model that better mimics human VCID and is compatible with live-animal MRI. The right and the left CCAs were temporarily ligated to 32- and 34-gauge needles with three ligations, respectively. After needle removal, CCA blood flow, cerebral blood flow, white matter injury (WMI) and cognitive function were measured. In male mice, needle removal led to ∼49.8% and ∼28.2% blood flow recovery in the right and left CCA, respectively. This model caused persistent and long-term cerebral hypoperfusion in both hemispheres (more severe in the left hemisphere), and WMI and cognitive dysfunction in ∼90% of mice, which is more reliable compared with other models. Importantly, these pathologic changes and cognitive impairments lasted for up to 24 weeks after surgery. The survival rate over 24 weeks was 81.6%. Female mice showed similar cognitive dysfunction, but a higher survival rate (91.6%) and relatively milder white matter injury. A novel, low-cost VCID model compatible with live-animal MRI with long-term outcomes was established.SIGNIFICANCE STATEMENT Bilateral common carotid artery (CCA) stenosis (BCAS) is an animal model mimicking carotid artery stenosis to study vascular cognitive impairment and dementia (VCID). However, current BCAS models have the disadvantages of high cost and incompatibility with magnetic resonance imaging (MRI) scanning due to metal implantation. We established a new asymmetric BCAS model by ligating the CCA to various needle gauges followed by an immediate needle removal. Needle removal led to moderate stenosis in the right CCA and severe stenosis in the left CCA. This needle model replicates the hallmarks of VCID well in ∼90% of mice, which is more reliable compared with other models, has ultra-low cost, and is compatible with MRI scanning in live animals. It will provide a new valuable tool and offer new insights for VCID research.


Asunto(s)
Disfunción Cognitiva , Demencia Vascular , Masculino , Ratones , Femenino , Humanos , Animales , Constricción Patológica/complicaciones , Disfunción Cognitiva/etiología , Modelos Animales de Enfermedad , Demencia Vascular/diagnóstico por imagen , Demencia Vascular/etiología , Demencia Vascular/patología , Cognición , Ratones Endogámicos C57BL
2.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 219-224, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38650130

RESUMEN

Mitochondrial DNA damage in retinal ganglion cells (RGCs) may be closely related to lesions of glaucoma. RGCs were cultured with different concentrations of glucose and grouped into 3 groups, namely normal control (NC) group, Low-Glu group, and High-Glu group. Cell viability was measured with cell counting kit-8, and cell apoptosis was measured using flow cytometry. The DNA damage was measured with comet assay, and the morphological changes of damaged mitochondria in RGCs were observed using TEM. Western blot analyzed the expression of MRE11, RAD50, and NBS1 protein. Cell viability of RGCs in Low-Glu and High-Glu groups were lower than that of NC group in 48 and 96 h. The cell apoptosis in NC group was 4.9%, the Low-Glu group was 12.2% and High-Glu group was 24.4%. The comet imaging showed that NC cells did not have tailings, but the low-Glu and high-Glu group cells had tailings, indicating that the DNA of RGCs had been damaged. TEM, mitochondrial membrane potential, ROS, mitochondrial oxygen consumption, and ATP content detection results showed that RGCs cultured with high glucose occurred mitochondrial morphology changes and dysfunction. MRE11, RAD50, and NBS1 protein expression associated with DNA damage repair pathway in High-Glu group declined compared with Low-Glu group. Mitochondrial DNA damage caused by high glucose will result in apoptosis of retinal ganglion cells in glaucoma.


Asunto(s)
Apoptosis , Supervivencia Celular , Daño del ADN , ADN Mitocondrial , Glucosa , Potencial de la Membrana Mitocondrial , Especies Reactivas de Oxígeno , Células Ganglionares de la Retina , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Glucosa/toxicidad , Glucosa/farmacología , ADN Mitocondrial/metabolismo , ADN Mitocondrial/genética , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Adenosina Trifosfato/metabolismo , Proteína Homóloga de MRE11/metabolismo , Proteína Homóloga de MRE11/genética , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ácido Anhídrido Hidrolasas/genética , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Humanos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Ensayo Cometa , Animales
3.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33500348

RESUMEN

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin-dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.


Asunto(s)
Alelos , Impresión Genómica , Proteínas Represoras/genética , Animales , Metilación de ADN/genética , Embrión de Mamíferos/metabolismo , Femenino , Ratones , RNA-Seq , Receptores Notch/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/genética
4.
Mikrochim Acta ; 191(6): 350, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806865

RESUMEN

Gold nanomaterials have been widely explored in electrochemical sensors due to their high catalytic property and good stability in multi-medium. In this paper, the reproducibility of the signal among batches of gold nanorods (AuNRs)-modified electrodes was investigated to improve the data stabilization and repeatability. Ordered and random self-assembled AuNRs-modified electrodes were used as electrochemical sensors for the simultaneous determination of dopamine (DA) and topotecan (TPC), with the aim of obtaining an improved signal stability in batches of electrodes and realizing the simultaneous determination of both substances. The morphology and structure of the assemblies were analyzed and characterized by UV-Vis spectra, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray powder diffraction (XRD). Electrochemical studies showed that the ordered AuNRs/ITO electrodes have excellent signal reproducibility among several individuals due to the homogeneous mass transfer in the ordered arrangement of the AuNRs. Under the optimized conditions, the simultaneous detection results of DA and TPC showed good linearity in the ranges 1.75-45 µM and 1.5-40 µM, and the detection limits of DA and TPC were 0.06 µM and 0.17 µM, respectively. The results showed that the prepared ordered AuNR/ITO electrode had high sensitivity, long-term stability, and reproducibility for the simultaneous determination of DA and TPC, and it was expected to be applicable for real sample testing.


Asunto(s)
Dopamina , Técnicas Electroquímicas , Electrodos , Oro , Límite de Detección , Nanotubos , Topotecan , Dopamina/análisis , Oro/química , Topotecan/análisis , Topotecan/química , Reproducibilidad de los Resultados , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Nanotubos/química , Humanos
5.
Inflamm Res ; 72(5): 1001-1019, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37014439

RESUMEN

OBJECTIVE AND DESIGN: The prevalence of intracranial aneurysms (IAs) has increased globally. We performed bioinformatics analysis to identify key biomarkers associated with IA formation. METHODS AND RESULTS: We conducted a comprehensive analysis combined with multi-omics data and methods to identify immune-related genes (IRGs) and immunocytes involved in IAs. Functional enrichment analyses showed enhanced immune responses and suppressed organizations of extracellular matrix (ECM) during aneurysm progression. xCell analyses showed that the abundance of B cells, macrophages, mast cells, and monocytes significantly increased from levels in control to unruptured aneurysms and to ruptured aneurysms. Of 21 IRGs identified by overlapping, a three-gene (CXCR4, S100B, and OSM) model was constructed through LASSO logistic regression. The diagnostic ability of the three biomarkers in discriminating aneurysms from the control samples demonstrated a favorable diagnostic value. Among the three genes, OSM and CXCR4 were up-regulated and hypomethylated in IAs, while S100B was down-regulated and hypermethylated. The expression of the three IRGs was further validated by qRT-PCR and immunohistochemistry and mouse IA model using scRNA-seq analysis. CONCLUSION: The present study demonstrated heightened immune response and suppressed ECM organization in aneurysm formation and rupture. The three-gene immune-related signature (CCR4, S100B, and OSM) model may facilitate IA diagnosis and prevention.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Animales , Ratones , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/epidemiología , Multiómica , Biomarcadores , Aneurisma Roto/diagnóstico , Aneurisma Roto/epidemiología , Aneurisma Roto/genética
6.
Transfus Apher Sci ; 62(2): 103576, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36117044

RESUMEN

BACKGROUND: ABO incompatibility is not a contraindication but would affect the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The dynamic change of blood phenotype is not only related to the patient's status, but also the basis for the implementation of compatible blood transfusion. The criteria for judging a complete transformation to donor-type and the principle of blood transfusion at relapse need to be unified. We aimed to illustrate the significance of blood group monitoring after allo-HSCT. MATERIAL AND METHODS: We collected 263 patients underwent ABO incompatible allo-HSCT from January 2010 to December 2019, and monitored blood type regularly according to the frequency of the patient's return visits till complete conversion or death. Non-parametric test was used to find differences among incompatible groups. We analyzed factors potentially influence blood type conversion by Binary Logistic model. Cox regression model was used to illustrate the relationship between blood-type conversion and prognosis. RESULTS: The median days of conversion were 107, 91 and 108 in major-, minor- and bidirectional groups respectively. Blood type conversion correlated with HLA compatibility (P = 0.012, OR=2.69) and acute graft-versus-host-disease (P = 0.001, OR=0.06). Patients with incomplete blood type conversion had a higher death rate than those with complete blood type conversion(P = 0.003, OR=3.703). DISCUSSION: Blood type monitoring can help to evaluate the prognosis of transplantation and assess the risk of death. It is recommended to monitor the changes of blood group antigens and antibodies, especially within a year after transplantation, to predict the risk of adverse events (such as GVHD, recurrence, death, etc.).


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Sistema del Grupo Sanguíneo ABO , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Incompatibilidad de Grupos Sanguíneos , Pronóstico , Enfermedad Injerto contra Huésped/etiología
7.
Altern Ther Health Med ; 29(1): 80-84, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36112791

RESUMEN

Context: Epidemiological data has shown that retinal detachment (RD) can occur at any age but has a poor prognosis in the adolescent population, which can cause huge obstacles to their life and learning. Although medications can achieve some curative effect, they have potential side effects and differences in individual efficacy. Objective: • The study intended to explore the clinical significance of visual training in improving recovery of postoperative visual function after external reduction of retinal detachment in adolescent patients. Design: The research team designed a prospective randomized controlled study. Setting: The study took place at Guiyang First People's Hospital in Guiyang, Guizhou, China. Participants: Participants were 110 adolescents with retinal detachments who underwent external reduction surgery, each on one eye for 110 eyes in total, and who were patients at the hospital between June 2015 and June 2019. Intervention: The research team assigned 52 participants to the visual-function training group, the intervention group, and 58 participants to the control group, according to the random-number-table method. Each group participated in training method for six months. Outcome Measures: To compare the groups, the research team measured visual function using the Visual Function scale (VF), binocular fusion function using the Worth Four Light Test (W4LT), and stereoscopic vision using the Titmus Stereo Test. The team obtained preoperative and postoperative data-at baseline, one day before surgery and postoperatively at one month and 3 months, and postintervention at 6 months. Results: Both groups had visual impairment after surgery. For visual function, the intervention group's scores after surgery increased gradually and were significantly higher than those of the control group at each follow-up time (P < .05). No significant difference in binocular fusion function existed between the groups at baseline or at one month after surgery (P > .05). At 3 months after surgery and postintervention, the proportions of participants in the intervention group with normal binocular fusion function were 86.54% and 88.46%, respectively, compared to that of the control group, at 68.97% and 70.69%, respectively. The intervention group's recovery was significantly better than that of the control group at 3 months after surgery and postintervention, at P < .028 and P < .022, respectively. No significant difference existed between the groups in stereoscopic vision at baseline, at 9.62% and 12.07%, respectively (P > .05). The proportion of participants in the intervention group with normal, binocular, stereoscopic vision increased gradually, and at one and 3 months after surgery and postintervention was 67.31%, 82.69%, and 88.46%, respectively. The intervention group's recovery was significantly better than that of the control group at one and 3 months after surgery and postintervention, at P < .028, P < .010, and P < .013, respectively. Conclusions: Visual training can effectively promote the recovery of visual function after external reduction of RD in adolescents and improve patients' prognoses. Moreover, long-term persistence can achieve significant effects, making the training worthy of clinical promotion.


Asunto(s)
Desprendimiento de Retina , Humanos , Adolescente , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Estudios Prospectivos , Relevancia Clínica , Agudeza Visual , China
8.
Molecules ; 28(16)2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37630390

RESUMEN

Guanine crystals with unique optical properties in organisms have been extensively studied and the biomineralization principles of guanine are being established. This review summarizes the fundamental physicochemical properties (solubility, tautomers, bands, and refractivity), polymorphs, morphology of biological and synthetic forms, and the reported biomineralization principles of guanine (selective recrystallization of amorphous precursor, preassembled scaffolds, additives, twinning, hypoxanthine doping, fluorescence, and assembly). The biomineralization principles of guanine will be helpful for the synthesis of guanine crystals with excellent properties and the design of functional organic materials for drugs, dyes, organic semiconductors, etc.

9.
Molecules ; 28(17)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37687147

RESUMEN

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

10.
Epilepsia ; 63(2): 463-473, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34874064

RESUMEN

OBJECTIVE: This work was undertaken to study the functional connectivity differences between non-seizure-free and seizure-free patients with temporal lobe epilepsy (TLE) and to identify imaging predictors for drug responsiveness in TLE. METHODS: In this prospective study, 52 patients with TLE who presented undetermined antiseizure medication responsiveness and 55 demographically matched healthy controls were sequentially recruited from Xiangya Hospital. Functional magnetic resonance imaging data were acquired during a Chinese version of the verbal fluency task. The patients were followed up until the outcome could be classified. The subject groups were compared in terms of activation profile, task-residual functional connectivity (trFC), and generalized psychophysiological interaction (gPPI) analyses. Moreover, we extracted imaging characteristics for logistic regression and receiver operating characteristic evaluation. RESULTS: With a mean follow-up of 1.1 years, we identified 27 non-seizure-free patients and 19 seizure-free patients in the final analyses. The Chinese character verbal fluency task successfully activated the language network and cognitive control network (CCN) and deactivated the default mode network (DMN). In the non-seizure-freedom group, the trFC between the hippocampus and bilateral brain networks was attenuated (p < .05, familywise error corrected). For the gPPI analysis, group differences were mainly located in the precuneus, middle frontal gyrus, and inferior parietal lobule (p < .001, uncorrected; k ≥ 10). The regression model presented high accuracy when predicting non-seizure-free patients (area under the curve = .879, 95% confidence interval = .761-.998). SIGNIFICANCE: In patients with TLE who would not achieve seizure freedom with current antiseizure medications, the functional connectivity between the hippocampus and central nodes of the DMN, CCN, and language network was disrupted, leading to language decline. Independent of hippocampal sclerosis, abnormalities, especially the effective connectivity from the hippocampus to the DMN, were predictive biomarkers of drug responsiveness in patients with TLE.


Asunto(s)
Epilepsia del Lóbulo Temporal , Encéfalo/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos
11.
Inflamm Res ; 71(10-11): 1347-1364, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36057911

RESUMEN

OBJECTIVES: This study aimed to identify the role of ferroptosis in intracranial aneurysm (IA). METHODS: GSE122897, GSE75436, GSE15629, and GSE75434 datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed ferroptosis-related genes (DEFRGs) were selected to construct a diagnostic model integrating with machine learning. Then, a consensus clustering algorithm was performed to classify IA patients into distinct ferroptosis-related clusters. Functional analyses, including GO, KEGG, GSVA, and GSEA analyses, were conducted to elucidate the underlying mechanisms. ssGSEA and xCell algorithms were performed to uncover the immune characteristics. RESULTS: We identified 28 DEFRGs between IAs and controls from the GSE122897 dataset. GO and KEGG results showed that these genes were enriched in cytokine activity, ferroptosis, and the IL-17 signaling pathway. Immune analysis showed that the IAs had higher levels of immune infiltration. A four FRGs model (MT3, CDKN1A, ZEP69B, and ABCC1) was established and validated with great IA diagnostic ability. We divided the IA samples into two clusters and found that cluster 2 had a higher proportion of rupture and immune infiltration. We identified 10 ferroptosis phenotypes-related markers in IAs. CONCLUSION: Ferroptosis and the immune microenvironment are closely associated with IAs, providing a basis for understanding the IA development.


Asunto(s)
Ferroptosis , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/metabolismo , Ferroptosis/genética , Perfilación de la Expresión Génica , Biomarcadores/metabolismo , Transducción de Señal
12.
Neurosurg Rev ; 45(4): 2909-2918, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35589870

RESUMEN

Seizures are the second most common manifestations of brain arteriovenous malformations (bAVMs). This study was conducted to investigate the clinical and angioarchitectural features of bAVMs with seizures and provide guidelines for the clinical management of these patients. We collected clinical and radiological data on patients with bAVMs diagnosed by digital subtraction angiography between January 2013 and December 2020 and dichotomized the patients into the seizures and non-seizures groups. We identified differences in demographic and angiographic features. Logistic regression and random forest (RF) models were developed and compared. The diagnostic capacity was assessed using receiver operating characteristic (ROC) curves. A nomogram was constructed, and the clinical impact was determined by decision curve analysis. A total of 414 patients with bAVMs were included in the analysis, of which 78 (18.8%) had bAVM-related seizures. In the multivariable logistic regression model, the location and side of bAVMs were independently associated with seizures. In RF models, the maximal diameter of veins and the cross-sectional area of feeding arteries and draining veins were the most important features. ROC curves showed that the RF model was not better than MLR in predicting seizures. Decision curve analysis revealed that the use of a constructed nomogram to stratify the seizure patients was beneficial at all threshold probabilities in our study. The side and location of bAVMs are specific angioarchitectural features independently associated with the occurrences of seizures with bAVMs.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales , Angiografía de Substracción Digital , Encéfalo , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Curva ROC , Estudios Retrospectivos
13.
Proc Natl Acad Sci U S A ; 116(10): 4643-4650, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30760601

RESUMEN

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function. To investigate the role of UCHL1 and its adduction by reactive lipids in inhibiting repair and recovery of function following ischemic injury, a knock-in (KI) mouse expressing the UCHL1 C152A mutation was generated. Neurons derived from KI mice had less cell death and neurite injury after hypoxia. UCHL1 C152A KI and WT mice underwent middle cerebral artery occlusion (MCAO) or sham surgery. White matter injury was significantly decreased in KI compared with WT mice 7 d after MCAO. Histological analysis revealed decreased tissue loss at 21 d after injury in KI mice. There was also significantly improved sensorimotor recovery in postischemic KI mice. K63- and K48-linked polyubiquitinated proteins were increased in penumbra of WT mouse brains but not in KI mouse brains at 24 h post MCAO. The UCHL1 C152A mutation preserved excitatory synaptic drive to pyramidal neurons and their excitability in the periinfarct zone; axonal conduction velocity recovered by 21 d post MCAO in KI mice in corpus callosum. These results demonstrate that UCHL1 activity is an important determinant of function after ischemia and further demonstrate that the C152 site of UCHL1 plays a significant role in functional recovery after stroke.


Asunto(s)
Axones/enzimología , Isquemia Encefálica/enzimología , Isquemia Encefálica/fisiopatología , Ubiquitina Tiolesterasa/metabolismo , Animales , Isquemia Encefálica/genética , Muerte Celular , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Mutación , Neuronas/citología , Neuronas/enzimología , Recuperación de la Función , Ubiquitina Tiolesterasa/genética
14.
J Neuroinflammation ; 18(1): 187, 2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34454529

RESUMEN

BACKGROUND: Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na+/H+ exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS). METHODS: Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR. RESULTS: Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP+ astrocytes and Iba1+ microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation. CONCLUSION: Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.


Asunto(s)
Astrocitos/efectos de los fármacos , Estenosis Carotídea/tratamiento farmacológico , Cognición/efectos de los fármacos , Gliosis/tratamiento farmacológico , Guanidinas/uso terapéutico , Sulfonas/uso terapéutico , Sustancia Blanca/efectos de los fármacos , Animales , Astrocitos/patología , Estenosis Carotídea/patología , Circulación Cerebrovascular/efectos de los fármacos , Disfunción Cognitiva/patología , Gliosis/patología , Guanidinas/farmacología , Inflamación/patología , Ratones , Microglía/efectos de los fármacos , Microglía/patología , Intercambiador 1 de Sodio-Hidrógeno/antagonistas & inhibidores , Sulfonas/farmacología , Sustancia Blanca/patología
15.
J Med Virol ; 93(5): 2805-2809, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33107614

RESUMEN

The emerging pandemic of coronavirus disease 2019 (COVID-19) has affected over 200 countries and resulted in a shortage of diagnostic resources globally. Rapid diagnosis of COVID-19 is vital to control the spreading of the disease, which, however, is challenged by limited detection capacity and low detection efficiency in many parts of the world. The pooling test may offer an economical and effective approach to increase the virus testing capacity of medical laboratories without requiring more laboratory resources such as laboratory workers, testing reagents, and equipment. In this study, the sample pools of 6 and 10 were detected by a real-time reverse transcription-polymerase chain reaction assay targeting ORF1ab and N genes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Each pool consisted of five or nine negative SARS-CoV-2 samples and one positive counterpart with varying viral loads. Two different strategies of sample pooling were investigated and the results were compared comprehensively. One approach was to pool the viral transport medium of the samples in the laboratory, and the other was to pool swab samples during the collection process. For swab pooling strategy, qualitative results of SARS-CoV-2 RNA, specific tests of ORF1ab and N genes, remained stable over the different pool sizes. Together, this study demonstrates that the swab pooling strategy may serve as an effective and economical approach for screening SARS-CoV-2 infections in large populations, especially in countries and regions where medical resources are limited during the pandemic and may thus be potential for clinical laboratory applications.


Asunto(s)
Prueba de COVID-19/métodos , COVID-19/diagnóstico , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Prueba de Ácido Nucleico para COVID-19/métodos , Proteínas de la Nucleocápside de Coronavirus/genética , Pruebas Diagnósticas de Rutina/métodos , Humanos , Tamizaje Masivo/métodos , Fosfoproteínas/genética , Poliproteínas/genética , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Manejo de Especímenes/métodos , Carga Viral , Proteínas Virales/genética
16.
Soft Matter ; 17(7): 1955-1962, 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33427846

RESUMEN

Biogenic guanine crystals exhibit excellent optical properties owing to their extremely high refractive index. However, there is no report related to the highly-ordered guanine assemblies in the synthetic systems. Herein, ß-phase anhydrous guanine (ß-AG) microrods were formed in mixed solvents of formamide and water in the presence of small organic molecules such as uric acid, pyrrole (Py), N-methyl-2-pyrrolidone (NMP), N-vinyl-2-pyrrolidone (NVP). The one-dimensional (1D) assembly of ß-AG microrods form spontaneously in water, which is the first reported highly ordered 1D assembly of organic micro- or nanocrystals in the solution. The obtained ß-AG microrods obtained in Py system can form reversible 1D assembly in water after being treated in organic solvents such as ethanol, acetone and isopropanol, which have high solubility in water. However, no reversible 1D assembly but only dispersed or aggregated guanine microrods formed in water after similar treatment in the other three organic solvents such as n-hexane, dichloroethane and petroleum ether with low solubility in water. Similar reversible assembly features can also be observed in other three systems, standard system, and NVP and NMP systems. The reversible 1D assemblies of guanine microrods in water and organic solvents with high solubility in water indicate that there is a strong interaction between the (100) planes of ß-AG microrods in water. The oriented 1D assembly of guanine microrods with long axes perpendicular to the horizontal magnetic field can form in water under magnetic field.


Asunto(s)
Guanina , Agua , 2-Propanol , Solubilidad , Solventes
17.
Soft Matter ; 17(19): 5025-5033, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33912882

RESUMEN

Similar to the crystal growth process, additives have a strong influence on the dissolution process of crystals. Studies on the dissolution process may shed light on understanding the biomineralization and bioinspired crystallization process. The influence of different kinds of additives including surfactants and polymers on the dissolution process of calcite {104} planes was investigated in detail in this work. The additives can be classified into three kinds according to their influence on the dissolution process of calcite under different concentration windows. The additives show three different kinds of dissolution behaviors with the increase of additive concentrations according to the tomographic variation of the calcite surface after the dissolution process. There are four dissolution modes of calcite while changing the additive concentrations in the solution. Rhombohedral etch pits with [4[combining macron]41] and [481[combining macron]] step edges are formed on the calcite {104} planes after the dissolution process at low additive concentrations (mode I). Calcite micropyramids begin to appear on the calcite surface and the densities of micropyramids increase with the increase of the additive concentrations until they cover the entire calcite surface after the dissolution process at medium additive concentrations (mode II). Instead of micropyramids, large pyramids with [481[combining macron]] and [4[combining macron]41] step edges and a size of about 50 µm form after the dissolution process at high additive concentrations (modes III and IV). We propose that the different anisotropic dissolution behaviors of calcite are strongly related to the concentrations and the adsorption features of the additives on the calcite surface. The additives may act as inhibitors of calcite dissolution, possibly through adsorption on calcite surfaces without preferred adsorption, or adsorption at specific kink sites or step edges. The influence of additives on the oriented dissolution of calcite is generally related to the adsorption density and homogeneity of additives on the calcite substrates.

18.
Nanotechnology ; 32(26)2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33684904

RESUMEN

In the past decades, defect engineering has become an effective strategy to significantly improve the hydrogen evolution reaction (HER) efficiency of electrocatalysts. In this work, a facile chemical vapor deposition (CVD) method is firstly adopted to demonstrate defect engineering in high-efficiency HER electrocatalysts of vanadium diselenide nanostructures. For practical applications, the conductive substrate of carbon cloth (CC) is selected as the growth substrate. By using a four-time CVD method, uniform three-dimensional microflowers with defect-rich small nanosheets on the surface are prepared directly on the CC substrate, displaying a stable HER performance with a low Tafel slope value of 125 mV dec-1and low overpotential voltage of 295 mV at a current density of 10 mA cm-2in alkaline electrolyte. Based on the results of x-ray photoelectron spectra and density functional theory calculations, the impressive HER performance originates from the Se vacancy-related active sites of small nanosheets, while the microflower/nanosheet homoepitaxy structure facilitates the carrier flow between the active sites and conductive substrate. All the results present a new route to achieve defect engineering using the facile CVD technique, and pave a novel way to prepare high-activity layered electrocatalysts directly on a conductive substrate.

19.
Neuroradiology ; 63(8): 1305-1311, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33475769

RESUMEN

PURPOSE: Previous studies have indicated that cerebral arterial morphology is linked to aging and some cerebrovascular diseases. However, the mechanisms of morphological changes remain unclear. This study evaluated age-related positional changes in the basilar artery (BA) bifurcation based on longitudinal computed tomography angiography (CTA) data. METHODS: This retrospective study evaluated clinical and imaging data from 72 subjects who underwent two CTA scans between July 2011 and August 2019. Three-dimensional (3D) models were reconstructed for each subject based on the two CTA scans with the longest separating interval. Skull landmarks were used to fuse the two models, and the fused model was used to evaluate positional changes in the BA bifurcation. Univariable and multivariable analyses were used to identify variables that were correlated to BA bifurcation shifting. Pearson's correlation test was used to analyze the correlation between the shifting distance and change in the BA bifurcation angle. RESULTS: Significant differences between aneurysm and non-aneurysm cases were observed in terms of sex (p = 0.004), CTA scan interval (p = 0.023), and BA bifurcation shifting distance (p = 0.007). Multivariable linear regression analysis revealed that the BA bifurcation shifting distance was significantly correlated with the CTA scan interval (p = 0.038) and the presence of aneurysms (p < 0.001). Furthermore, the shifting distance was positively correlated with widening of the BA bifurcation angle (p = 0.002). CONCLUSIONS: Aging-related widening of the BA bifurcation angle may be related to distal shifting of the BA bifurcation's position, and larger distal shifting of the BA bifurcation may be associated with the risk of aneurysm formation.


Asunto(s)
Arteria Basilar , Aneurisma Intracraneal , Arteria Basilar/diagnóstico por imagen , Angiografía Cerebral , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Estudios Longitudinales , Estudios Retrospectivos , Cráneo
20.
BMC Med Inform Decis Mak ; 21(1): 142, 2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33941166

RESUMEN

BACKGROUND: In many cases, both the rupture rate of cerebral arteriovenous malformation (bAVM) in patients and the risk of endovascular or surgical treatment (when radiosurgery is not appropriate) are not low, it is important to assess the risk of rupture more cautiously before treatment. Based on the current high-risk predictors and clinical data, different sample sizes, sampling times and algorithms were used to build prediction models for the risk of hemorrhage in bAVM, and the accuracy and stability of the models were investigated. Our purpose was to remind researchers that there may be some pitfalls in developing similar prediction models. METHODS: The clinical data of 353 patients with bAVMs were collected. During the creation of prediction models for bAVM rupture, we changed the ratio of the training dataset to the test dataset, increased the number of sampling times, and built models for predicting bAVM rupture by the logistic regression (LR) algorithm and random forest (RF) algorithm. The area under the curve (AUC) was used to evaluate the predictive performances of those models. RESULTS: The performances of the prediction models built by both algorithms were not ideal (AUCs: 0.7 or less). The AUCs from the models built by the LR algorithm with different sample sizes were better than those built by the RF algorithm (0.70 vs 0.68, p < 0.001). The standard deviations (SDs) of the AUCs from both prediction models with different sample sizes displayed wide ranges (max range > 0.1). CONCLUSIONS: Based on the current risk predictors, it may be difficult to build a stable and accurate prediction model for the hemorrhagic risk of bAVMs. Compared with sample size and algorithms, meaningful predictors are more important in establishing an accurate and stable prediction model.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales , Algoritmos , Área Bajo la Curva , Encéfalo , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/epidemiología , Modelos Logísticos
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