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1.
Mol Psychiatry ; 28(6): 2398-2411, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37085711

RESUMEN

Central nervous system axons have minimal capacity to regenerate in adult brains, hindering memory recovery in Alzheimer's disease (AD). Although recent studies have shown that damaged axons sprouted in adult and AD mouse brains, long-distance axonal re-innervation to their targets has not been achieved. We selectively visualized axon-growing neurons in the neural circuit for memory formation, from the hippocampus to the prefrontal cortex, and showed that damaged axons successfully extended to their native projecting area in mouse models of AD (5XFAD) by administration of an axonal regenerative agent, diosgenin. In vivo transcriptome analysis detected the expression profile of axon-growing neurons directly isolated from the hippocampus of 5XFAD mice. Secreted protein acidic and rich in cysteine (SPARC) was the most expressed gene in axon-growing neurons. Neuron-specific overexpression of SPARC via adeno-associated virus serotype 9 delivery in the hippocampus recovered memory deficits and axonal projection to the prefrontal cortex in 5XFAD mice. DREADDs (Designer receptors exclusively activated by designer drugs) analyses revealed that SPARC overexpression-induced axonal growth in the 5XFAD mouse brain directly contributes to memory recovery. Elevated levels of SPARC on axonal membranes interact with extracellular rail-like collagen type I to promote axonal remodeling along their original tracings in primary cultured hippocampal neurons. These findings suggest that SPARC-driven axonal growth in the brain may be a promising therapeutic strategy for AD and other neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Diosgenina , Ratones , Animales , Enfermedad de Alzheimer/genética , Diosgenina/metabolismo , Diosgenina/farmacología , Diosgenina/uso terapéutico , Osteonectina/metabolismo , Osteonectina/uso terapéutico , Axones/metabolismo , Hipocampo/metabolismo , Modelos Animales de Enfermedad , Ratones Transgénicos
2.
Neuroendocrinology ; 114(3): 223-233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37827139

RESUMEN

INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.


Asunto(s)
Epilepsia , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/genética , Epilepsia/epidemiología , Epilepsia/genética , Glucosa , China , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales/metabolismo
3.
BMC Neurol ; 22(1): 130, 2022 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-35382802

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) affects the occurrence and prognosis of acute ischemic stroke (AIS). However, the impact of diabetes on thrombus characteristics is unclear. The relationship between the composition and ultrastructure of clots and DM with admission hyperglycemia was investigated. METHODS: Consecutive patients with AIS who underwent endovascular thrombus retrieval between June 2017 and May 2021 were recruited. The thrombus composition and ultrastructure were evaluated using Martius scarlet blue stain and scanning electron microscopy. Clot perviousness was evaluated via thrombus attenuation increase on computed tomography angiography (CTA) versus non-contrast CT. Patients with admission hyperglycemia DM (ahDM) and those without DM (nonDM) were compared in terms of thrombus composition, ultrastructure, and perviousness. RESULTS: On admission, higher NIHSS scores (17 vs. 12, respectively, p = 0.015) was evident in ahDM patients. After the 90-day follow-up, the rates of excellent outcomes (mRS 0-1) were lower in patients with ahDM (16.6%, p = 0.038), but functional independence (mRS 0-2) and handicapped (mRS 3-5) were comparable between patients with ahDM and nonDM. The outcome of mortality was higher in patients with ahDM (33.3%, p = 0.046) than in nonDM patients. Clots in patients with ahDM had more fibrin (39.4% vs. 25.0%, respectively, p = 0.007), fewer erythrocyte components (21.2% vs. 41.5%, respectively, p = 0.043), equivalent platelet fraction (27.7% vs. 24.6%, respectively, p = 0.587), and higher WBC counts (4.6% vs. 3.3%, respectively, p = 0.004) than in nonDM patients. The percentage of polyhedral erythrocytes in thrombi was significantly higher in ahDM patients than in nonDM patients (68.9% vs. 45.6%, respectively, p = 0.007). The proportion of pervious clots was higher in patients nonDM than in patients with ahDM (82.61% vs. 40%, respectively, p = 0.026). CONCLUSION: Patients with ahDM presented with greater stroke severity on admission and poorer functional outcomes after 3 months. Clots in patients with ahDM had more fibrin, leucocytes, and fewer erythrocyte components than in patients nonDM. The content of polyhedral erythrocytes and impervious clots proportion were significantly higher in thrombi of patients with AIS and ahDM. Further research is required to validate these findings.


Asunto(s)
Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Hiperglucemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hiperglucemia/complicaciones , Accidente Cerebrovascular/etiología , Trombectomía/métodos , Trombosis/complicaciones , Trombosis/patología
4.
BMC Neurol ; 21(1): 398, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34645398

RESUMEN

BACKGROUND: The significance of carotid webs (CaWs) in ischemic stroke is becoming acknowledged. Histological features of clot composition in situ and secondary cerebrovascular embolized thrombi caused by CaW have not been described concurrently. Understanding clots' histological composition is essential for understanding the pathophysiology of clot formation in CaW. CASE PRESENTATION: A 50-year-old male patient with acute ischemic stroke, which was believed to be caused by ipsilateral CaW, was admitted to the hospital. Mechanical thrombectomy was used to retrieve thromboemboli from the middle cerebral artery. One month thereafter, the patient underwent carotid endarterectomy, and in situ CaW thrombi were retrieved. Histological analysis by hematoxylin and eosin staining revealed that histopathologic embolized thrombi appeared as typical mixed thrombi, 46.03% fibrin/platelet ratio, 48.12% RBCs, and 5.85% white blood cells. In situ thrombi had a higher fibrin/platelet ratio (68.0%), fewer RBCs (17.2%), and 14.8% white blood cells. CONCLUSION: The histopathology of large vessel occlusion stroke embolized thrombi by CaW is similar to that of other stroke etiologies. However, the clot composition of embolized thrombi significantly differs from that of in situ thrombi. CaW's in situ thrombi showed predominantly fibrin, and embolized thrombi had equivalent contents of red blood cells and fibrin/platelets. Histopathological differences between in situ and embolized thrombi suggest new research directions for the etiology of embolization. Further studies are required to confirm these results.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Trombosis , Fibrina , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/terapia , Trombectomía , Trombosis/etiología
5.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-34445457

RESUMEN

Strigolactones (SLs) regulate plant shoot development by inhibiting axillary bud growth and branching. However, the role of SLs in wintersweet (Chimonanthus praecox) shoot branching remains unknown. Here, we identified and isolated two wintersweet genes, CCD7 and CCD8, involved in the SL biosynthetic pathway. Quantitative real-time PCR revealed that CpCCD7 and CpCCD8 were down-regulated in wintersweet during branching. When new shoots were formed, expression levels of CpCCD7 and CpCCD8 were almost the same as the control (un-decapitation). CpCCD7 was expressed in all tissues, with the highest expression in shoot tips and roots, while CpCCD8 showed the highest expression in roots. Both CpCCD7 and CpCCD8 localized to chloroplasts in Arabidopsis. CpCCD7 and CpCCD8 overexpression restored the phenotypes of branching mutant max3-9 and max4-1, respectively. CpCCD7 overexpression reduced the rosette branch number, whereas CpCCD8 overexpression lines showed no phenotypic differences compared with wild-type plants. Additionally, the expression of AtBRC1 was significantly up-regulated in transgenic lines, indicating that two CpCCD genes functioned similarly to the homologous genes of the Arabidopsis. Overall, our study demonstrates that CpCCD7 and CpCCD8 exhibit conserved functions in the CCD pathway, which controls shoot development in wintersweet. This research provides a molecular and theoretical basis for further understanding branch development in wintersweet.


Asunto(s)
Arabidopsis , Calycanthaceae/genética , Dioxigenasas , Genes de Plantas , Proteínas de Plantas , Raíces de Plantas , Plantas Modificadas Genéticamente , Arabidopsis/enzimología , Arabidopsis/genética , Calycanthaceae/enzimología , Dioxigenasas/biosíntesis , Dioxigenasas/genética , Proteínas de Plantas/biosíntesis , Proteínas de Plantas/genética , Raíces de Plantas/enzimología , Raíces de Plantas/genética , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética
6.
Cerebrovasc Dis ; 49(4): 382-387, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32756062

RESUMEN

INTRODUCTION: Safety of carotid artery stenting (CAS) in patients having carotid stenosis with coexistent unruptured intracranial aneurysms (UIAs) is rarely reported. Thus, we studied the 3-month outcome of CAS in the presence of coexistent UIAs in our institution. METHODS: A retrospective analysis of patients receiving CAS at our institution from September 2011 to December 2019 was carried out. Patients were stratified into 2 groups: group of CAS with UIAs (CAS-UIA) and group of CAS without UIAs (CAS). The main complications within 3 months after stenting were TIA, ischemic stroke, symptomatic intracranial hemorrhage (sICH), rupture of UIAs, and death. The baseline characteristics and complications of the 2 groups were compared. RESULTS: Five hundred fifty-six patients (CAS, n = 468; CAS-UIA, n = 88) were included and 604 stenting procedures were performed. More patients had hypertension in the CAS-UIA group (87.5 vs. 73.7%, p = 0.006). There was no significant difference in TIAs, ischemic stroke, sICH, and death within 3 months after stenting between the CAS and CAS-UIA groups. None of the 113 coexistent UIAs detected in 88 patients had aneurysm rupture within 3 months after CAS. CONCLUSIONS: In our large cohort of CAS patients, coexistent UIAs are not uncommon. Stenting of a carotid artery in the presence of coexistent UIAs could be conducted safely. Together with 3-month dual antiplatelet therapy, CAS did not increase the rupture risk of the coexistent UIAs within 3 months.


Asunto(s)
Estenosis Carotídea/terapia , Procedimientos Endovasculares/instrumentación , Aneurisma Intracraneal/complicaciones , Stents , Anciano , Aneurisma Roto/etiología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/mortalidad , Terapia Antiplaquetaria Doble , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/mortalidad , Hemorragias Intracraneales/etiología , Ataque Isquémico Transitorio/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Factores de Tiempo , Resultado del Tratamiento
7.
Int J Mol Sci ; 21(13)2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-32630004

RESUMEN

In Alzheimer's disease (AD), amyloid ß (Aß) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aß have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aß deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aß, they could hardly be recovered. Therefore, we speculated that only removal of Aß was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aß-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aß-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Axones/efectos de los fármacos , Magnoliopsida , Fitoterapia , Extractos Vegetales/uso terapéutico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Axones/metabolismo , Células Cultivadas , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Extractos Vegetales/farmacología
8.
J Reconstr Microsurg ; 35(7): 499-504, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30836413

RESUMEN

BACKGROUND: End-to-end, end-to-side, and side-to-side microvascular anastomoses are the main types of vascular bypass grafting used in microsurgery and neurosurgery. Currently, there has been no animal model available for practicing all three anastomoses in one operation. The aim of this study was to develop a novel animal model that utilizes the rat abdominal aorta (AA), common iliac arteries (CIAs), and the median sacral artery (MSA) for practicing these three types of anastomosis. METHODS: Eight adult Sprague-Dawley rats were anesthetized and then laparotomized. The AA, MSA, and bilateral CIAs were exposed and separated from the surrounding tissues. The length and diameter of each artery were measured. The relatively long segment of the AA without major branches was selected to perform end-to-end anastomosis. One side of the CIAs (or AA) and MSA were used for end-to-side anastomosis. The bilateral CIAs were applied to a side-to-side and another end-to-side anastomosis. RESULTS: Anatomical dissection of the AA, CIAs, and MSA was successfully performed on eight Sprague-Dawley rats; four arterial-to-arterial anastomoses were possible for each animal. The AA trunk between the left renal artery and right iliolumbar arteries was 15.60 ± 0.76 mm in length, 1.59 ± 0.15 mm in diameter, for an end-to-end anastomosis. The left CIA was 1.06 ± 0.08 mm in diameter, for an end-to-side anastomosis with the right CIA. The MSA was 0.78 ± 0.07 mm in diameter, for another end-to-side anastomosis with the right CIA or AA. After finishing end-to-side anastomosis in the proximal part of bilateral CIAs, the distal portion was juxtaposed for an average length of 5.6 ± 0.25 mm, for a side-to-side anastomosis. CONCLUSION: This model can comprehensively and effectively simulate anastomosis used in revascularization procedures and can provide more opportunities for surgical education, which may lead to more routine use in microvascular anastomosis training.


Asunto(s)
Anastomosis Quirúrgica/educación , Microcirugia/educación , Procedimientos Quirúrgicos Vasculares/educación , Animales , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley
9.
CNS Neurosci Ther ; 30(7): e14827, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38992878

RESUMEN

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.


Asunto(s)
Anticonvulsivantes , Epilepsia , Levetiracetam , Saliva , Humanos , Levetiracetam/farmacocinética , Levetiracetam/sangre , Femenino , Saliva/química , Saliva/metabolismo , Embarazo , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangre , Anticonvulsivantes/análisis , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/sangre , Adulto Joven , Monitoreo de Drogas/métodos , Piracetam/análogos & derivados , Piracetam/análisis , Piracetam/farmacocinética , Piracetam/sangre , Estudios Prospectivos , Estudios de Cohortes , Espectrometría de Masas en Tándem/métodos
10.
J Pharm Sci ; 113(5): 1385-1394, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38176454

RESUMEN

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.


Asunto(s)
Anticonvulsivantes , Epilepsia , Embarazo , Humanos , Femenino , Levetiracetam , Anticonvulsivantes/farmacocinética , Mujeres Embarazadas , Epilepsia/tratamiento farmacológico , Peso Corporal , China
11.
Ultrasound Med Biol ; 50(8): 1134-1142, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38692941

RESUMEN

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.


Asunto(s)
Inteligencia Artificial , Ecocardiografía , Humanos , Femenino , Ecocardiografía/métodos , Masculino , Persona de Mediana Edad , Adulto , Solución Salina , Anciano , Algoritmos , Medios de Contraste , Adolescente , Adulto Joven
12.
Mol Neurobiol ; 60(3): 1250-1266, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36437381

RESUMEN

Galectin-1 (Gal-1), a member of the Galectin family, is expressed in various tissues and responsible for multiple biological activities. Previous studies reported that extracellular Gal-1 participated in axonal growth and repair, and Gal-1 knockout mice exhibited memory impairment. However, no study has demonstrated the direct contribution of intracellular Gal-1 upregulation in neurons to promoting axonal regeneration in the brain and recovering memory function. In the present study, we found that axonal growth is promoted by overexpression of Gal-1 via adeno-associated virus serotype 9 delivery in primary cultured hippocampal neurons. Moreover, Gal-1 was expressed on the membranes of growth cones in hippocampal neurons and interacted with a novel axonal guidance molecule, Secernin-1, which was secreted from prefrontal cortex (PFC) neurons. Gal-1-overexpression-driven axonal growth was enhanced when recombinant (extracellular) Secernin-1 was treated to the axonal site in a neuron device chamber. Direct binding of extracellular Secernin-1 with Gal-1 was detected through immunoprecipitation and immunocytochemistry, demonstrating that Gal-1 possibly works as an axonal guidance receptor for Secernin-1 in hippocampal neurons. In the PFC, the expression of Gal-1 in axonal shafts and terminals of hippocampal neurons was decreased in the 5XFAD mouse model of Alzheimer's disease (AD). Overexpression of Gal-1 in hippocampal neurons recovered memory deficits and induced axonal regeneration toward the PFC in 5XFAD mice. This study suggests that the enhanced interaction of Secernin-1 and Gal-1 can be harnessed as a therapeutic strategy for long-distance and direction-specific axonal regeneration in AD.


Asunto(s)
Axones , Galectina 1 , Proteínas del Tejido Nervioso , Animales , Ratones , Axones/fisiología , Galectina 1/metabolismo , Ratones Noqueados , Neuronas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Regeneración
13.
Front Neurol ; 14: 1128366, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37260610

RESUMEN

Intracranial dural arteriovenous fistula (DAVF) can induce remote myelopathy via spinal perimedullary venous drainage. In the present study, we report a rare case of intracranial pial arteriovenous malformation (AVM)-related myelopathy. A 52-year-old man presented with progressive, predominantly proximal weakness and muscle atrophy in bilateral upper limbs, urinary retention, and hyperreflexia in bilateral upper and lower limbs. Brain and cervicothoracic MRI showed longitudinal myelopathy extending from the medulla oblongata to the T6 level, with perimedullary enlarged veins from the C1 to T12 level, and remarkable enhancement in bilateral anterior horns from the C2 to C7 level. Cerebral angiography revealed a choroidal fissure AVM, which was supplied by the left anterior choroidal artery and drained exclusively by an inferior ventricular vein descending toward the spinal perimedullary veins. After endovascular embolization of the feeding pedicle, nidus, and proximal segment of the draining vein, the patient's neurological deficits rapidly improved, and a significant recovery was achieved 3 months after the procedure. This rare case indicates that intracranial pial AVM can also cause extensive congestive myelopathy with similar mechanisms underlying intracranial and craniocervical DAVF cases, and gray matter in the spinal cord might be more susceptible to ischemia induced by intraspinal venous hypertension.

14.
Front Plant Sci ; 14: 1186816, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37416877

RESUMEN

Introduction: Metabolic engineering of anthocyanin synthesis is an active research area for pigment breeding and remains a research hotspot involving AtPAP1 and ZmLc transcription factors. Caladium bicolor is a desirable anthocyanin metabolic engineering receptor, with its abundant leaf color and stable genetic transformation system. Methods: We transformed C. bicolor with AtPAP1 and ZmLc and successfully obtained transgenic plants. We then used a combination of metabolome, transcriptome, WGCNA and PPI co-expression analyses to identify differentially expressed anthocyanin components and transcripts between wild-type and transgenic lines. Results: Cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and peonidin-3-O-rutinoside are the main components of anthocyanins in the leaves and petioles of C. bicolor. Exogenous introduction of AtPAP1 and ZmLc resulted in significant changes in pelargonidins, particularly pelargonidin-3-O-glucoside and pelargonidin-3-O-rutinoside in C. bicolor. Furthermore, 5 MYB-TFs, 9 structural genes, and 5 transporters were found to be closely associated with anthocyanin synthesis and transport in C. bicolor. Discussion: In this study, a network regulatory model of AtPAP1 and ZmLc in the regulation of anthocyanin biosynthesis and transport in C. bicolor was proposed, which provides insights into the color formation mechanisms of C. bicolor, and lays a foundation for the precise regulation of anthocyanin metabolism and biosynthesis for economic plant pigment breeding.

15.
Epilepsia Open ; 8(2): 456-465, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36808903

RESUMEN

OBJECTIVE: A right-to-left shunt (RLS) can mediate the hypoxic state, and hypoxemia is relevant for the development of drug-resistant epilepsy (DRE). The objective of this study was to identify the relationship between RLS and DRE and further investigate the contribution of RLS to the oxygenation state in patients with epilepsy (PWEs). METHODS: We performed a prospective observational clinical study of PWEs who underwent contrast medium transthoracic echocardiography (cTTE) between January 2018 and December 2021 at West China Hospital. The collected data included demographics, clinical features of epilepsy, antiseizure medications (ASMs), RLS identified by cTTE, electroencephalography (EEG), and magnetic resonance imaging (MRI). Arterial blood gas was also assessed in PWEs with or without RLS. The association between DRE and RLS was quantified using multiple logistic regression, and the parameters of oxygen levels were furtherly analyzed in PWEs with or without RLS. RESULTS: A total of 604 PWEs who completed cTTE were included in the analysis, of which 265 were diagnosed with RLS. The proportion of RLS was 47.2% in the group of DRE, and the proportion of RLS was 40.3% in the group of non-DRE. Having RLS was associated with DRE in multivariate logistic regression analysis (adjusted OR = 1.53, P = 0.045). In the analysis of blood gas, the partial oxygen pressure in PWEs with RLS was lower than those without RLS (88.74 mmHg versus 91.84 mmHg, P = 0.044). SIGNIFICANCE: Right-to-left shunt could be an independent risk factor of DRE, and low oxygenation might be a possible reason.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Foramen Oval Permeable , Humanos , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/complicaciones , Ecocardiografía , Epilepsia/complicaciones , Medios de Contraste , Hipoxia/complicaciones , Oxígeno
16.
J Neuroendocrinol ; 35(3): e13250, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36942563

RESUMEN

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m2 ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m2 ), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m2 ), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.


Asunto(s)
Epilepsia , Hormonas Peptídicas , Síndrome del Ovario Poliquístico , Femenino , Humanos , Adolescente , Estudios Transversales , Hormona Luteinizante , Factores de Riesgo , Epilepsia/tratamiento farmacológico , Levetiracetam/uso terapéutico , Hormona Antimülleriana/uso terapéutico , Obesidad
17.
Front Plant Sci ; 14: 1328603, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38312354

RESUMEN

Chimonanthus praecox is a famous traditional flower in China with high ornamental value. It has numerous varieties, yet its classification is highly disorganized. The distinctness, uniformity, and stability (DUS) test enables the classification and nomenclature of various species; thus, it can be used to classify the Chimonanthus varieties. In this study, flower traits were quantified using an automatic system based on pattern recognition instead of traditional manual measurement to improve the efficiency of DUS testing. A total of 42 features were quantified, including 28 features in the DUS guidelines and 14 new features proposed in this study. Eight algorithms were used to classify wintersweet, and the random forest (RF) algorithm performed the best when all features were used. The classification accuracy of the outer perianth was the highest when the features of the different parts were used for classification. A genetic algorithm was used as the feature selection algorithm to select a set of 22 reduced core features and improve the accuracy and efficiency of the classification. Using the core feature set, the classification accuracy of the RF model improved to 99.13%. Finally, K-means was used to construct a pedigree cluster tree of 23 varieties of wintersweet; evidently, wintersweet was clustered into a single class, which can be the basis for further study of genetic relationships among varieties. This study provides a novel method for DUS detection, variety identification, and pedigree analysis.

19.
Chin Neurosurg J ; 8(1): 37, 2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36461080

RESUMEN

BACKGROUND: Endovascular treatment (EVT) is an alternative option for symptomatic intracranial atherosclerotic disease (ICAD). However, the effect of EVT treatment on ICAD plaques is still unclear. This study describes the ICAD plaque characteristics after EVT treatment and analyzes the effect of different EVT treatments on plaque characteristics. METHOD: From 2017 January to 2022 January, ICAD patients who underwent endovascular treatment and had follow-up high-resolution magnetic resonance image (HRMRI) were enrolled in the study. Multiple plaque characteristics, including plaque enhancement, plaque burden, were measured based on preoperative, and follow-up HRMRI. Plaque characteristics and postoperative plaque changes were analyzed between different treatment groups. RESULT: Finally, 50 intracranial atherosclerotic plaques in 45 patients were included. Including 28 male patients and 17 female, media age 63.0 years old. Among 50 plaques, 41 received percutaneous angioplasty (including 22 plain balloons and 19 drug-coated balloons (DCB)) and the other 9 underwent stenting. Stenosis rate, plaque burden and eccentricity index at the lesion site were significantly decreased after EVT compared with preoperative periods (p <0.001). And only the DCB group showed a significant reduction in plaque enhancement at follow-up (p < 0.001). No significant preoperative and postoperative changes in other plaque characteristics were found. CONCLUSION: EVT treatment could compromise the characteristics of intracranial periarterial atherosclerotic plaques, and DCB treatment may result in a reduction in plaque enhancement after treatment.

20.
Front Neurol ; 13: 1008328, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36176562

RESUMEN

Introduction: Kinking of the cervical carotid or vertebral artery is a common structural abnormality in patients with cerebrovascular disease. However, there is no consensus about the relationship between kinking and ischemic stroke/TIA. We aim to determine the effect of arterial kinking on ischemic stroke/TIA. Methods: A retrospective study was performed on patients who underwent cerebral angiography with DSA between January 2014 and December 2018. Demographic information and comorbidities were recorded. Each anatomical circulation system was defined as an observation unit. Kinking and stenosis of each circulation unit were recorded. Ischemia stroke or TIA within 6 months and its location were assessed as an outcome. Logistic regression with a generalized estimating equation approach was used for the analysis. Results: A total of 1,062 patients (mean age 57.9 ± 14.5 years, 740 males and 322 females) were included in the study. Of the patients, 369 (35%) had kinking and 771 (73%) had ischemic stroke/TIA. There were 110 left anterior, 90 right anterior, and 308 posterior circulation units, among which 343 had mild, 160 had moderate, and 243 had severe kinking. Multivariate regression analysis showed that ischemic stroke/TIA was associated with severe kinking (OR 1.39, 95% CI 1.03-1.88, P = 0.03). Posterior circulation was more vulnerable to acute ischemia than left anterior and right anterior circulation (OR 3.58, 95% CI 2.81-4.56, P < 0.0001). Conclusion: Severe kinking of the cervical carotid or vertebral artery may be associated with a higher risk of ischemic stroke/TIA, especially when the kinking is located in the posterior circulation.

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