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1.
Complement Ther Med ; 83: 103055, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38782080

RESUMEN

BACKGROUND: Dizziness often occurs after microvascular decompression (MVD), and therapeutic options are limited. The aim of this trial was to determine the potential efficacy of transcutaneous electrical acupoint stimulation (TEAS), against dizziness and its safety in patients undergoing MVD. METHODS: Adult patients scheduled to undergo MVD for hemifacial spasm under total intravenous anesthesia were randomized at a 1:1 ratio to receive, after extubation, 30-min TEAS in the mastoid region as well as Fengchi acupoints (GB20) and Neiguan acupoints (PC6) or 30-min sham stimulation. The primary outcome was the incidence of dizziness at 2 h after surgery. Secondary outcomes included dizziness, postoperative nausea and vomiting (PONV) or headache severity, rescue medication, changes in intraocular pressure before and after surgery, length of stay, dizziness symptoms 4 weeks after discharge, and surgical complications. RESULTS: A total of 86 patients (51.9 ± 9.4 years of age; 67 women) were enrolled. One patient (in the TEAS arm) was excluded from analysis due to conversion to sevoflurane anesthesia. The rate of dizziness at 2 h after surgery was 31.0 % (13/42) in the TEAS arm vs. 53.5 % (23/43) in the sham control arm (P = 0.036). TEAS was also associated with significantly lower severity of dizziness, based on a 10-point scale, during the first 24 h after surgery. None of the other secondary efficacy outcomes differed significantly between the two arms. All postoperative complications were Clavien-Dindo grade I or II. The rate of postoperative complications was 21.4 % (9/42) in the TEAS arm vs. 16.3 % (7/43) in the sham control arm (P = 0.544). CONCLUSIONS: Compared with sham control, TEAS was associated with a lower incidence of dizziness within 2 h and lower severity of dizziness within 24 h post-operatively, but no improvement in other outcomes, in adult patients undergoing MVD for hemifacial spasm.


Asunto(s)
Puntos de Acupuntura , Mareo , Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Persona de Mediana Edad , Femenino , Masculino , Espasmo Hemifacial/cirugía , Estimulación Eléctrica Transcutánea del Nervio/métodos , Mareo/etiología , Mareo/terapia , Cirugía para Descompresión Microvascular/métodos , Cirugía para Descompresión Microvascular/efectos adversos , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/terapia
2.
Heliyon ; 10(6): e27722, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38501006

RESUMEN

Found in many fruits and plants, Ursolic acid (UA), a pentacyclic triterpene that occurs naturally, is recognized for its anti-cancer effects, especially in combating glioblastoma. However, the intricate molecular mechanisms underpinning its anti-tumor actions are still not fully understood, despite the recognition of these effects. By examining the functions of epithelial-mesenchymal transition (EMT) and angiogenesis, crucial for glioblastoma progression, and their regulation through Transforming Growth Factor Beta (TGFß) - a key marker for glioblastoma, our research aims to fill this knowledge gap. This study explores how ursolic acid can block the progression of glioblastoma by precisely targeting TGFß-triggered EMT and angiogenesis. The findings show that UA successfully blocks the spread, movement, and invasion of glioblastoma cells. Accompanying this, there is a significant reduction in the expression of TGFß and crucial EMT indicators like snail and vimentin. Furthermore, UA shows a reduction in angiogenesis that depends on the dosage, highlighted by decreased vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs). Interestingly, increased TGFß expression in U87 and U251 glioblastoma cell lines was found to weaken UA's anti-tumor properties, shedding more light on TGFß's critical function in glioblastoma's pathology. Supporting these laboratory results, UA also showed considerable inhibition of tumor growth in a glioblastoma xenograft mouse model. Overall, our research emphasizes Ursolic acid's promise as a new treatment for glioblastoma and clarifies its action mechanism, mainly by inhibiting TGFß signaling and thereby EMT and angiogenesis.

3.
Medicine (Baltimore) ; 103(7): e36837, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363944

RESUMEN

BACKGROUND: Intracerebral hemorrhage (ICH) secondary injury is serious and affects patient's prognosis. The Zhenzhu Pills used to treat subacute ICH in Tibet has shown to have a certain curative effect. Network pharmacology and molecular docking technology are employed to explore the potential mechanism of Zhenzhu Pills. The components and potential targets of Zhenzhu Pills were screened from the Traditional Chinese Medicine Systems Pharmacology database. The Gene Expression Omnibus Series 24265 was used to screen differentially expressed genes between perihematomal tissue and normal brain. METHODS: The herbs-components-targets network was established, with weighted eigenvalue to identify the core components and targets of Zhenzhu Pills treatment of ICH secondary injury. Targets' bioinformatics enrichment was proceeded by gene ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, molecular docking was used to identify the hydrogen bonding activity between the key components and action targets. RESULTS: Five herbal drugs were screened from Traditional Chinese Medicine Systems Pharmacology database, with a total of 48 components and 234 targets. The Gene Expression Omnibus Series 24265 dataset was evaluated and 920 differentially expressed genes were identified. A total of 29 intersection targets of Zhenzhu Pills were explored in the treatment of ICH secondary injury. Drugs-components-targets network analysis showed that the pivotal targets were prostaglandin G/H synthase 2, interleukin 6, heme oxygenase-1, vascular endothelial growth factor, and vascular cell adhesion molecule 1, and the core components were quercetin, luteolin, and kaempferol. Gene ontology and KEGG pathway enrichment analysis showed that biological processes such as cell chemotaxis, wound healing, leukocyte migration, and regulation of body fluid levels played an important role in the secondary injury of ICH. The results of KEGG pathway analysis were mainly related to advanced glycation end products-receptor for advanced glycation end products signal pathway and tumor necrosis factor signal pathway. Molecular docking of 3 flavonoids with 5 core targets with the results also showed active hydrogen bonding. CONCLUSIONS: This study provides insights into the potential mechanisms of Zhenzhu Pills in the treatment of secondary injuries resulting from ICH and highlights specific components, targets, and molecular pathways involved in this therapeutic effect. These possible therapeutic mechanisms include inhibiting inflammation, edema, oxidative stress, and so on.


Asunto(s)
Lesiones Encefálicas , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Factor A de Crecimiento Endotelial Vascular , Hemorragia Cerebral/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China
4.
Mol Neurobiol ; 61(8): 5950-5957, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38261256

RESUMEN

Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.


Asunto(s)
Epilepsia , Predisposición Genética a la Enfermedad , Análisis de la Aleatorización Mendeliana , Enfermedades Neurodegenerativas , Polimorfismo de Nucleótido Simple , Humanos , Polimorfismo de Nucleótido Simple/genética , Epilepsia/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/epidemiología , Estudio de Asociación del Genoma Completo , Factores de Riesgo
5.
Artículo en Inglés | MEDLINE | ID: mdl-38290454

RESUMEN

Objective: This study investigates the efficacy of DWI combined with intraoperative ultrasound for deep brain glioma treatment, analyzing changes in Karnofsky performance status (KPS) scores and imaging signs. Objectives include elucidating the approach's advantages, addressing knowledge gaps, and contributing insights into its effectiveness for enhancing deep brain glioma management. Methods: In this retrospective study, we analyzed a total of 346 patients with deep brain glioma who underwent surgical treatment at our hospital from July 2015 to January 2022. After applying inclusion and exclusion criteria, 310 patients were selected and categorized into a control group (n = 150) and an observation group (n = 160) based on different auxiliary techniques of surgical treatment. The degree of resection and Karnofsky performance status (KPS) scores were assessed at 1 day preoperatively, 1 week, and 1 month postoperatively for both groups. Additionally, we conducted a comprehensive analysis of DWI and ultrasound imaging signs among patients with different grades of deep brain glioma. The study duration covered the specified period, and statistical analyses were performed to evaluate the outcomes. Results: In our study, the observation group demonstrated significantly improved resection degrees, with a total resection rate of 82.50% compared to the control group's 65.33%. Preoperative Karnofsky performance status scores showed no significant difference between groups (P > .05), but postoperative scores at 1 week and 1 month were significantly higher in the observation group (P < .05). Intraoperative ultrasound and DWI revealed distinct imaging signs differentiating low-grade and high-grade patients. These results highlight the efficacy of DWI combined with intraoperative ultrasound resection in enhancing resection outcomes and influencing postoperative Karnofsky performance status. Conclusions: DWI combined with intraoperative ultrasonic resection in deep brain glioma has a significant effect, with specific imaging signs, which can effectively improve the total resection rate and KPS score, and is worthy of clinical promotion. DWI combined with intraoperative ultrasound has important clinical significance in the resection of deep brain gliomas. The better resection results and improved postoperative Karnofsky performance-status score that we observed suggest a possible benefit in patient outcomes, which could influence treatment strategies. The precise imaging signs identified by this method provide valuable guidance for targeted and effective tumor resection.

6.
Eur J Neurol ; 31(2): e16121, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37933887

RESUMEN

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.


Asunto(s)
Estimulación Encefálica Profunda , Distonía , Trastornos Distónicos , Síndrome de Meige , Núcleo Subtalámico , Humanos , Síndrome de Meige/terapia , Síndrome de Meige/etiología , Distonía/terapia , Calidad de Vida , Estimulación Encefálica Profunda/efectos adversos , Estudios Prospectivos , Trastornos Distónicos/terapia , Resultado del Tratamiento , Globo Pálido
8.
Eur J Pharmacol ; 958: 176074, 2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37742812

RESUMEN

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

9.
Exp Ther Med ; 26(1): 339, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37383368

RESUMEN

The current overall incidence of subarachnoid hemorrhage (SAH) is ~9/100,000 individuals/year and rupture of an intracranial aneurysm is the main cause of SAH, accounting for ~85% of cases. Only a small number of cases of paraplegia after intracranial aneurysmal SAH have so far been reported and its pathogenesis has remained to be fully elucidated. The present study reports the case of a patient with an aneurysm localized in the medial and inferior lateral wall of the C5 segment of the right internal carotid artery that was treated by coil interventional embolization. The muscle strength of both lower extremities of the patient was grade I and grade 0 before and after the operation, respectively. Lumbar and thoracic magnetic resonance imaging examinations revealed slight hematoma in the subarachnoid space below the L2 level. At two weeks after the operation, the muscle strength of both lower extremities was grade II, while the muscle strength was grade III and grade V at 30 and 60 days after the operation, respectively.

10.
Eur J Pharmacol ; 948: 175697, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-36997048

RESUMEN

BACKGROUND: Platycodin D (PD) is a major bioactive component of Platycodon grandiflorum, a medicinal herb that is widely used in China, and is effective against various human cancers, including glioblastoma multiforme (GBM). S phase kinase-related protein 2 (Skp2) is oncogenic and overexpressed in various human tumors. It is highly expressed in GBM and its expression is correlated with tumor growth, drug resistance and poor prognosis. In this study, we investigated whether inhibition of glioma progression by PD is mediated by decreasing expression of Skp2. METHODS: Cell Counting Kit-8 (CCK-8) and Transwell assays were used to determine the effects of PD on GBM cell proliferation, migration, and invasion in vitro. mRNA and protein expression were determined by real time polymerase chain reaction (RT-PCR) and western blotting, respectively. The U87 xenograft model was used to verify the anti-glioma effect of PD in vivo. Expression levels of Skp2 protein were analyzed by immunofluorescence staining. RESULTS: PD suppressed proliferation and motility of GBM cells in vitro. The expression of Skp2 in U87 and U251 cells was significantly reduced by PD. PD mainly decreased the cytoplasmic expression of Skp2 in glioma cells. Skp2 protein expression was downregulated by PD, resulting in upregulation of its downstream targets, p21and p27. The inhibitory effect of PD was enhanced by Skp2 knockdown in GBM cells and reversed in cells with Skp2 overexpression. CONCLUSION: PD suppresses glioma development by regulation of Skp2 in GBM cells.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Neoplasias Encefálicas/genética , Glioma/patología , Proliferación Celular , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica
11.
Biomed Res Int ; 2023: 7656069, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36845638

RESUMEN

Objectives: Delayed cerebral ischemia (DCI) contributes to poor aneurysm prognosis. Subarachnoid hemorrhage and DCI have irreversible and severe consequences once they occur; therefore, early prediction and prevention are important. We investigated the risk factors for postoperative complications of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring mechanical ventilation in intensive care and validated a prediction model. Methods: We retrospectively analyzed patients with aSAH who were treated in a French university hospital neuro-ICU between January 2010 and December 2015. The patients were randomized into a training group (144) and verification groups (60). Nomograms were validated in the training and verification groups, where receiver operating characteristic curve analysis was used to verify model discrimination; calibration curve and Hosmer-Lemeshow test were used to determine model calibration; and decision curve analysis (DCA) was used to verify clinical validity of the model. Results: External ventricular drain (EVD), duration of mechanical ventilation, and treatment were significantly associated in the univariate analysis; EVD and rebleeding were significantly associated with the occurrence of DCI after aSAH. Binary logistic regression was used to select five clinicopathological characteristics to predict the occurrence of DCI in patients with aSAH requiring mechanical ventilation nomograms of the risk of DCI. Area under the curve values for the training and verification groups were 0.768 and 0.246, with Brier scores of 0.166 and 0.163, respectively. Hosmer-Lemeshow calibration test values for the training and verification groups were x 2 = 3.824 (P = 0.923) and x 2 = 10.868 (P = 0.285), respectively. Calibration curves showed good agreement. DCA indicated that the training and verification groups showed large positive returns in the broad risk range of 0-77% and 0-63%, respectively. Conclusions: The predictive model of concurrent DCI in aSAH has theoretical and practical values and can provide individualized treatment options for patients with aSAH who require mechanical ventilation.


Asunto(s)
Isquemia Encefálica , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Estudios Retrospectivos , Respiración Artificial/efectos adversos , Infarto Cerebral/complicaciones , Isquemia Encefálica/complicaciones
12.
Neurosurgery ; 92(5): 1073-1079, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728352

RESUMEN

BACKGROUND: Bilateral pallidal deep brain stimulation (DBS) has been broadly accepted as a feasible surgical procedure for treating various forms of dystonia, but its effects on motor function, neuropsychological status, and mood in patients with Meige syndrome have rarely been examined. OBJECTIVE: To evaluate the effects of bilateral globus pallidus internus DBS (GPi-DBS) on the motor performance, quality of life, neuropsychological status, and mood of patients with primary Meige syndrome. METHODS: Between January 2015 and April 2019, the database of 35 patients with Meige syndrome who underwent bilateral GPi-DBS in our institution was retrospectively reviewed. The severity of dystonia, health-related quality of life, cognitive function, and mood were assessed using standardized and validated rating scales at baseline. Repeat assessment of the same domains was performed at 1 year and 3 years after neurostimulation in a similar manner. RESULTS: One year and 3 years after bilateral GPi-DBS, Burke-Fahn-Marsden Dystonia Rating Scale movement scores were improved by 65% and 72% and Burke-Fahn-Marsden Dystonia Rating Scale disability scores were improved by 49% and 57%, respectively. The significant improvement in health-related quality of life observed at 1 year was sustained at 3 years. Relative to baseline and to the 1-year assessment, cognitive functions and mood remained stable after 3 years of neurostimulation. No deaths or life-threatening events were reported over the study period. CONCLUSION: Bilateral GPi-DBS is a safe and effective approach for medically refractory Meige syndrome that can improve motor function and quality of life without cognitive and mood side effects.


Asunto(s)
Estimulación Encefálica Profunda , Distonía , Trastornos Distónicos , Síndrome de Meige , Humanos , Globo Pálido , Síndrome de Meige/terapia , Síndrome de Meige/etiología , Distonía/etiología , Resultado del Tratamiento , Estudios Retrospectivos , Estimulación Encefálica Profunda/métodos , Calidad de Vida , Trastornos Distónicos/etiología
13.
Sci Rep ; 12(1): 19980, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36411289

RESUMEN

To analyse the microlesion effect (MLE) in the globus pallidus interna (GPi) of deep brain stimulation (DBS) in patients with Meige syndrome. Thirty-two patients with primary Meige syndrome who underwent GPi-DBS in this study. Burke-Fahn-Marsden Dystonia Rating Scale scores (BFMDRS-M) were obtained for the evaluation of clinical symptoms at 3 days before DBS (baseline), 24 h after DBS surgery, once weekly for 1 month until electrical stimulation, 6 months postoperatively and 12 months after surgery. Twenty-seven patients had MLE after GPi-DBS. The mean time of BFMDRS-M scores maximal improvement from MLE was 35.9 h postoperatively (range, 24-48 h), and the mean scores improved by 49.35 ± 18.16%. At 12 months after surgery, the mean BFMDRS-M scores improved by 50.28 ± 29.70%. There was a positive correlation between the magnitude of MLE and the motor score at 12 months after GPi-DBS (R2 = 0.335, p < 0.05). However, there was no correlation between the duration of MLE and DBS improvement. Most Meige syndrome patients who underwent GPi-DBS and had MLE benefited from MLE. For Meige syndrome, MLE might be a predictive factor for patient clinical symptom improvement from DBS.


Asunto(s)
Estimulación Encefálica Profunda , Distonía , Síndrome de Meige , Humanos , Síndrome de Meige/terapia , Globo Pálido/cirugía , Globo Pálido/fisiología , Estimulación Encefálica Profunda/efectos adversos , Resultado del Tratamiento
14.
Medicine (Baltimore) ; 101(39): e30853, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36181021

RESUMEN

BACKGROUND: Evodiae fructus has been shown to have anti-glioblastoma multiforme (GBM) effects. However, its anti-GBM active components and mechanism remain unclear. In this study, the active components of evodiae fructus were screened by network pharmacology to explore the possible molecular mechanism of resistance to GBM. MATERIALS AND METHODS: The main active ingredients of evodiae fructus were derived from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Batch-traditional Chinese medicine (TCM). TCMSP and Swiss absorption, distribution, metabolism and elimination (ADME) predict genetic targets for ingredients that meet pharmacological criteria. GBM-related targets were obtained from DisGeNet, GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and TCGA. A Venn diagram was used to obtain the common targets of evodiae fructus and GBM. Protein-protein interaction (PPI) networks and component-disease target networks were constructed using Cytoscape 3.8.1 software for visualization. GBM gene differential expression was visualized by VolcaNoseR, and potential targets were enriched by Gene Ontology (GO) function and annotated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by SRplot. Molecular docking verification was conducted using AutoDock Vina software. RESULTS: According to the screening conditions, 24 active components and 80 drug targets were obtained. The PPI network contains 80 proteins. The molecular docking verification showed the molecular docking affinity of the core active compounds in evodiae fructus with CASP3, JUN, EGFR, and AKT1. CONCLUSIONS: This study preliminarily identified the various molecular targets and multiple pathways of evodiae fructus against GBM.


Asunto(s)
Medicamentos Herbarios Chinos , Evodia , Caspasa 3 , Medicamentos Herbarios Chinos/farmacología , Receptores ErbB , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en Red
15.
Front Oncol ; 12: 785345, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35957872

RESUMEN

Epithelial-to-mesenchymal transition (EMT) and angiogenesis have emerged as two pivotal events in cancer progression. Paeoniflorin has been widely studied in experimental models and clinical trials for cancer treatment because of its anti-cancer property. However, the underlying mechanisms of paeoniflorin in EMT and angiogenesis in glioblastoma was not fully elucidated. The present study aimed to investigate whether paeoniflorin inhibits EMT and angiogenesis, which involving c-Met suppression, while exploring the potential ways of c-Met degradation. In our study, we found that paeoniflorin inhibited EMT via downregulating c-Met signaling in glioblastoma cells. Furthermore, overexpressing c-Met in glioblastoma cells abolished the effects of paeoniflorin on EMT. Moreover, paeoniflorin showed anti-angiogenic effects by suppressing cell proliferation, migration, invasion and tube formation through downregulating c-Met in human umbilical vein endothelial cells (HUVECs). And c-Met overexpression in HUVECs offset the effects of paeoniflorin on angiogenesis. Additionally, paeoniflorin induced autophagy activation involving mTOR/P70S6K/S6 signaling and promoted c-Met autophagic degradation, a process dependent on K63-linked c-Met polyubiquitination. Finally, paeoniflorin suppressed mesenchymal makers (snail, vimentin, N-cadherin) and inhibited angiogenesis via the identical mechanism in an orthotopic xenograft mouse model. The in vitro and in vivo experiments showed that paeoniflorin treatment inhibited EMT, angiogenesis and activated autophagy. What's more, for the first time, we identified c-Met may be a potential target of paeoniflorin and demonstrated paeoniflorin downregulated c-Met via K63-linked c-Met polyubiquitination-dependent autophagic degradation. Collectively, these findings indicated that paeoniflorin inhibits EMT and angiogenesis via K63-linked c-Met polyubiquitination-dependent autophagic degradation in human glioblastoma.

16.
Int J Med Sci ; 19(8): 1235-1240, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928716

RESUMEN

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.


Asunto(s)
Edema Encefálico , Receptor Toll-Like 4 , Animales , Edema Encefálico/complicaciones , Edema Encefálico/etiología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Ratones , Microglía , Saponinas
17.
Biomed Res Int ; 2022: 2488139, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35996545

RESUMEN

Objective: Glioblastoma is one of the most common and fatal malignancies in adults. Current treatment is still not optimistic. Glioblastoma (GBM) transports RNA to platelets in the blood system via microvesicles, suggesting that platelet RNA can be a potential diagnostic and therapeutic target. The roles of specific platelet RNAs in treatment of GBM are not well understood. Methods: Platelet RNA profiling of 8 GBM and 12 normal samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between tumors and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of up- and downregulated genes. miRNA was predicted by miRTarBase, TargetScan, and miRDB databases. circBase and circBank were used for circRNA prediction. ceRNA (circRNA-mRNA-miRNA) network was constructed to investigate the potential interactions. Results: 22 genes were upregulated and 9 genes were downregulated. There are only two genes (CCR7 and FAM102A) that connect to miRNAs (hsa-let-7a-5p, hsa-miR-1-3p). We assessed the overall survival rates by Kaplan-Meier plotter, and relative expression of GBM and subtypes for overlapped mRNA (CCR7 and FAM102A) were evaluated, and further, we obtained circRNAs (has-circ-0015164, hsa-circ-0003243) by circBank and circBase and bind sites through the CSCD database. Finally, a ceRNA network (circRNA-mRNA-miRNA) was constructed based on 2 miRNAs, 2 mRNAs, and 2 circRNAs by Cytoscape. This study focused on potential mRNA and ceRNA biomarkers to targeted treatment of GBM and provided ideas for clinical treatment through the combination of hematology and oncology. Conclusion: The findings of this study contribute to better understand the relationship between GBM and the blood system (platelets) and might lay a solid foundation for improving GBM molecule and gene diagnosis and prognosis.


Asunto(s)
Glioblastoma , MicroARNs , Adulto , Biomarcadores/metabolismo , Biología Computacional , Redes Reguladoras de Genes/genética , Glioblastoma/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CCR7/genética
18.
Sci Rep ; 12(1): 12213, 2022 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842469

RESUMEN

There is lacking research on risk factors and prediction models associated with Post-hemorrhagic hydrocephalus (PHH). Thus, this present study aimed to analyze the risk factors of PHH and establish a risk-scoring system through a large-scale study. A retrospective study of 382 patients with intracranial hemorrhage assessed age, history and diagnosis, Glasgow coma score (GCS), and fever time. After univariate and logistic regression analysis, a risk scoring system was established according to independent risk factors and evaluated using the area under the curve (AUC). Of the 382 patients, 133 (34.8%) had PHH, 43 (11.3%) received surgical treatment. Factor classification showed that age > 60 years old [odds ratio (OR): 0.347, II = 5 points], GCS < 5 (OR: 0.09, IV = 10 points), GCS 6‒8 (OR = 0.232, III = 6 points), fever time > 9 (OR: 0.202, III = 7 points), fever time 5-9 (OR: 0.341, II = 5 points), CSF-TP x time > 14,4000 group (OR: 0.267, IV = 6 points), and CSF-TP x time 9,601‒14,400 group (OR: 0.502, III = 3 points) were independent risk factors. The result of the receiver operating characteristic (ROC) prediction showed that AUC = 0.790 (0.744‒0.836). Low-risk (IV-VII), moderate (VIII-X), and high-risk group (XI-XIII) incidence of PHH were 11.76%, 50.55%, and 70.00% (p < 0.001), respectively. The coincidence rates in the validation cohort were 26.00%, 74.07%, and 100.0% (p < 0.001), respectively. AUC value was 0.860 (0.780‒0.941). The predictive model was conducive to determining the occurrence of PHH and facilitating early intervention.


Asunto(s)
Hidrocefalia , Adulto , Área Bajo la Curva , Humanos , Hidrocefalia/epidemiología , Hidrocefalia/etiología , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo
19.
BMC Anesthesiol ; 22(1): 132, 2022 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-35490219

RESUMEN

BACKGROUND: Postoperative nausea and vomiting is common in patients receiving microvascular decompression. In the current study, we examined whether postoperative nausea and vomiting is associated with reduced intraocular pressure (IOP) after microvascular decompression, a measure that reflects intracranial pressure. METHODS: This is a prospective cohort study. Adult patients scheduled for microvascular decompression surgery for hemifacial spasm between January 2020 and August 2020 were eligible. IOP was measured immediately before anesthesia induction and 30 min after patients regained complete consciousness using non-contact tonometry. IOP reduction was defined by at least 1 mmHg decrease vs. preoperative baseline. The primary outcome was vomiting on postoperative day 1. RESULTS: A total of 103 subjects were enrolled. IOP was reduced in 56 (54.4%) subjects. A significantly greater proportion of patients with IOP reduction had vomiting on postoperative day 1 (51.8% (29/56) vs. 23.4% (11/47) in those without IOP reduction; p = 0.003). In the multivariate regression analysis, vomiting on postoperative day 1 was associated with female sex [odds ratio = 7.87, 95% CI: 2.35-26.32, p = 0.001] and IOP reduction [odds ratio = 2.93, 95% CI: 1.13-7.58, p = 0.027]. CONCLUSIONS: In patients undergoing microvascular decompression surgery, postoperative IOP reduction is associated with postoperative vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000029083 . Registered 13 January 2020.


Asunto(s)
Oftalmopatías , Cirugía para Descompresión Microvascular , Adulto , Femenino , Humanos , Presión Intraocular , Cirugía para Descompresión Microvascular/efectos adversos , Náusea y Vómito Posoperatorios/epidemiología , Estudios Prospectivos , Tonometría Ocular
20.
Front Aging Neurosci ; 14: 848100, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370610

RESUMEN

Objectives: The subthalamic nucleus (STN) has been shown to be a safe and effective deep brain stimulation (DBS) surgical target for the treatment of Meige syndrome. The aim of this study was to compare changes in brain metabolism before and 6 months after STN-DBS surgery. Methods: Twenty-five patients with primary Meige syndrome underwent motor function assessment, including the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) and positron emission tomography with an 18[F]-fluorodeoxyglucose scan before and 6 months after STN-DBS surgery. For the voxelwise metabolic change assessment, the p-value was controlled for multiple comparisons using the familywise error rate. Results: There was a significant decrease in BFMDRS-M scores 6 months after STN-DBS, from 10.02 ± 3.99 to 4.00 ± 2.69 (p < 0.001). The BFMDRS-D scores also decreased significantly from 4.52 ± 2.90 to 0.64 ± 1.29 (p < 0.001). In the left hemisphere, hypermetabolism was found in the occipital lobe, superior parietal gyrus, postcentral gyrus and thalamus. In the right hemisphere, hypermetabolism was found in the lentiform nucleus, precuneus and precentral gyrus in patients with Meige syndrome receiving DBS. In addition, the bilateral inferior temporal gyrus and middle frontal gyrus exhibited glucose hypermetabolism. Conclusion: Our findings indicate that STN-DBS has a significant effect on metabolic level in the brain, which may be an important mechanism for the treatment of Meige syndrome using STN-DBS.

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