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PURPOSE: The previous studies have suggested that serum homocysteine (Hcy) and vitamin B levels are potentially related to autism spectrum disorder (ASD). However, the causality between their concentrations and ASD risk remains unclear. To elucidate this genetic association, we used a Mendelian randomization (MR) design. METHODS: For this MR analysis, 47 single-nucleotide polymorphisms (SNPs)-13 related to Hcy, 13 to folate, 14 to vitamin B6, and 7 to vitamin B12-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). Our study used three approaches to calculate the MR estimates, including inverse-variance weighted (IVW) method, MR-Egger method, and weighted median (WM) method. Among these, the IVW method served as our primary MR method. False discovery rate (FDR) was implemented to correct for multiple comparisons. We also performed a series of sensitivity analyses, including Cochran's Q test, MR-Egger's intercept, MR-PRESSO, leave-one-out analysis, and the funnel plot. RESULTS: Univariable Mendelian randomization (UVMR) analysis revealed a statistical association between serum vitamin B12 levels and ASD risk (OR = 1.68, 95% CI 1.12-2.52, P = 0.01) using the IVW method. However, neither the WM method (OR = 1.57, 95% CI 0.93-2.66, P = 0.09) nor the MR-Egger method (OR = 2.33, 95% CI 0.48-11.19, P = 0.34) was significantly association with higher levels of serum vitamin B12 and ASD risk. Additionally, we found no evidence of causal relationships between serum levels of vitamin B6, folate, Hcy, and ASD risk. After correcting for the FDR, the causality between serum vitamin B12 levels and ASD risk remained significant (q value = 0.0270). Multivariate Mendelian randomization (MVMR) analysis indicated an independent association between elevated serum vitamin B12 levels and the risk of ASD (OR = 1.74, 95% CI 1.03-2.95, P = 0.03) using the IVW method, but this finding was inconsistent when using the WM method (OR = 1.73, 95% CI 0.89-3.36, P = 0.11) and MR-Egger method (OR = 1.60, 95% CI 0.95-2.71, P = 0.08). Furthermore, no causal associations were observed for serum levels of vitamin B6 and folate in MVMR analysis. Sensitivity analyses confirmed that these results were reliable. CONCLUSION: Our study indicated that elevated serum vitamin B12 levels might increase the risk of ASD. The potential implications of our results for ASD risk warrant validation in randomized clinical trials.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Trastorno del Espectro Autista/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Vitaminas , Ácido Fólico , Vitamina B 6 , Vitamina B 12 , HomocisteínaRESUMEN
OBJECTIVE: To validate the different predictive scoring scales in the Chinese population with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface antibody (Ab)-mediated autoimmune encephalitis (AE). METHODS: We retrospectively reviewed the charts of 174 consecutive patients from October 2018 to December 2022, whose serum and cerebrospinal fluid samples were tested for neuronal surface Abs. The antibody prevalence in epilepsy and encephalopathy (APE2), antibodies contributing to focal epilepsy signs and symptoms (ACES), "obvious" indications for neural antibody testing in epilepsy or seizures (ONES) checklist, and the combinations were used to validate the predictive models of neuronal surface Ab-mediated AE. RESULTS: A total of 139 patients with new-onset epileptic seizures or epilepsy of unknown etiology were enrolled. Abs were detected in 37 patients (26.6%). The APE2/ONES reflex score had the highest sensitivity (89.2%) and lowest specificity (41.7%). The ACES score had the lowest sensitivity (67.5%) and highest specificity (64.7%). Variations in the performance were observed in the different types of AE. 100% of patients with anti-γ-aminobutyric acid B-B receptor encephalitis were predicted by ONES, APE2/ONES reflex, and ACES/ONES reflex scores. Only 75% of patients with anti-N-methyl-D-aspartate receptor encephalitis were predicted by the APE2/ONES and ACES/ONES reflex scores. CONCLUSION: Our study was the first to validate various predictive scoring scales in the Chinese cohort of patients with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface Ab-mediated AE. Based upon clinical suspicion, more than one scoring scale should be performed to predict the chance of AE in those patients.
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Enfermedades Autoinmunes del Sistema Nervioso , Encefalopatías , Epilepsia , Humanos , Estudios Retrospectivos , Epilepsia/epidemiología , Encefalopatías/complicaciones , Convulsiones/epidemiología , Anticuerpos , Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , AutoanticuerposRESUMEN
OBJECTIVE: To evaluate the association between the number of stent retriever (SR) passes and clinical outcome after mechanical thrombectomy (MT) in patients with acute ischemic stroke(AIS). METHODS: We retrospectively analyze data collected from consecutive patients with large vessel occlusion (LVO) in anterior circulation treated with MT. Baseline characteristics, number of SR passes, symptomatic intracranial hemorrhage (sICH), clinical outcome measured by modified Rankin Scale (mRS) at 90 days after MT were collected. Multivariate logistic regression analysis was performed to assess the association between number of SR passes and patients' clinical outcome. RESULTS: 134 patients with LVO achieved successful reperfusion (mTICI 2B/3) were enrolled. Univariate analysis showed that patients with favorable outcomes were less likely to need more than three passes of SR (9.8%vs39.7%, p = 0.001). In a multivariable analysis, baseline NIHSS score (OR 0.922, 95%CI 0.859â¼0.990, p = 0.025), more than three passes of SR (OR 0.284, 95%CI0.091â¼0.882, p = 0.030) and symptomatic intracranial hemorrhage (OR 0.116,95%CI0.021â¼0.650, p = 0.014) each independently predicted poor outcome after MT at 90 days. CONCLUSION: The need for more than three passes of SR may be used as an independent predictor of poor outcome after MT in patients with acute ischemic stroke at 90 days.
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Isquemia Encefálica/terapia , Stents , Accidente Cerebrovascular/terapia , Trombectomía/instrumentación , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Trombectomía/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Understanding the characteristics of neuromyelitis optica spectrum disorder (NMOSD) with recurrent short partial transverse myelitis (SPTM), which is very rare, contributes to the differential diagnosis of multiple sclerosis (MS). We present two Chinese aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD cases who had at least twice SPTM during 4 and 6 years of follow-up, respectively. Their SPTMs have been mild and responded well to corticosteroids just like in the case of MS. The findings highlight the need of searching for serum AQP4-IgG (cell-based assay strongly recommended) in patients with recurrent SPTM and suggest that those patients may have a mild acute attack phase and favorable long-term prognosis.
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Acuaporina 4/inmunología , Mielitis Transversa , Neuromielitis Óptica , Adulto , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G , Mielitis Transversa/sangre , Mielitis Transversa/etiología , Mielitis Transversa/fisiopatología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/fisiopatología , Pronóstico , Recurrencia , Adulto JovenRESUMEN
Background and purpose: Malignant cerebral edema (MCE) is one of serious complications with high mortality following endovascular treatment (EVT) for acute ischemic stroke (AIS) with large vessel occlusion. We aimed to investigate the relationship between postoperative neutrophil-to-lymphocyte ratio (NLR) and MCE after EVT. Methods: The clinical and imaging data of 175 patients with AIS of anterior circulation after EVT were studied. Admission and postoperative NLR were determined. The presence of MCE was evaluated on the computed tomography performed 24 h following EVT. The clinical outcomes were measured using the modified Rankin Scale (mRS) at 90-day after onset. Univariate and multivariate regression analyses were used to analyze the relationship between postoperative NLR and MCE. Optimal cutoff values of postoperative NLR to predict MCE were defined using receiver operating characteristic analysis. Results: MCE was observed in 24% of the patients who underwent EVT and was associated with a lower rate of favorable clinical outcomes at 90-day. Multivariate logistic regression analysis demonstrated that baseline Alberta Stroke Program Early CT Score (ASPECT) score (OR = 0.614, 95% CI 0.502-0.750, p = 0.001), serum glucose (OR = 1.181, 95% CI 1.015-1.374, p = 0.031), and postoperative NLR (OR = 1.043, 95% CI 1.002-1.086, p = 0.041) were independently associated with MCE following EVT for AIS with large vessel occlusion. Postoperative NLR had an area under the receiver operating characteristic curve of 0.743 for prediction MCE, and the optimal cutoff value was 6.15, with a sensitivity and specificity of 86.8% and 55%. Conclusion: Elevated postoperative NLR is independently associated with malignant brain edema following EVT for AIS with large vessel occlusion, and may serve as an early predictive indicator for MCE after EVT.
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Documented cases of ipsilateral ptosis caused by midbrain infarction remain rare. Herein, we present a patient with isolated ipsilateral ptosis that was initially considered to be a consequence of myasthenia gravis but was subsequently attributed to ventral midbrain infarction. We also discuss the possible underlying mechanisms; ipsilateral ptosis in our patient was attributed to selective damage of the levator palpebral muscle branch of the oculomotor nerve. The patient was started on aspirin (200 mg once daily) and atorvastatin (40 mg once daily). Improvement in ptosis occurred from day 5 of admission, and the patient was subsequently discharged. Ptosis disappeared 1 month after onset. This report describes an extremely rare case of ventral midbrain infarction presenting with isolated ipsilateral ptosis. Careful examination, including magnetic resonance imaging, is essential in such patients, especially in those with multiple cerebrovascular risk factors.
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Blefaroptosis , Imagen por Resonancia Magnética , Mesencéfalo , Humanos , Blefaroptosis/etiología , Mesencéfalo/diagnóstico por imagen , Mesencéfalo/patología , Masculino , Aspirina/uso terapéutico , Atorvastatina/uso terapéutico , Femenino , Anciano , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/complicaciones , Persona de Mediana EdadRESUMEN
BACKGROUND: Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association. METHODS: We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran's Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings. RESULTS: No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892-0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888-0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy. CONCLUSION: While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.
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Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302-1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237-1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395-1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019-1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007-1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02-1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%-12.10%) for any stroke, 11.77% (95% CI: 10.58%-12.97%) for IS, 10.62% (95% CI: 8.04%-13.20%) for LAS, and 7.57% (95% CI: 6.79%-8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.
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Trastorno del Espectro Autista , Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/epidemiología , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND AND PURPOSE: Parenchymal hematoma is a dreaded complication of mechanical thrombectomy after acute ischemic stroke. This study evaluated whether blood-brain barrier permeability measurements based on CT perfusion could be used as predictors of parenchymal hematoma after successful recanalization and compared the predictive value of various permeability parameters in patients with acute ischemic stroke. METHODS: We enrolled 53 patients with acute ischemic stroke who underwent mechanical thrombectomy and achieved successful recanalization. Each patient underwent CT, CT angiography, and CT perfusion imaging before treatment. We used relative volume transfer constant (rKtrans ) values, relative permeability-surface area product (rP·S), and relative extraction fraction (rE) to evaluate preoperative blood-brain barrier permeability in the delayed perfusion area. RESULTS: Overall, 22 patients (37.7%) developed hemorrhagic transformation after surgery, including 10 patients (16.9%) with hemorrhagic infarction and 11 patients (20.8%) with parenchymal hematoma. The rP·S, rKtrans , and rE of the hypoperfusion area in the parenchymal hematoma group were significantly higher than those in the hemorrhagic infarction and no-hemorrhage transformation groups (p < .01). We found that rE and rP·S were superior to rKtrans in predicting parenchymal hematoma transformation after thrombectomy (P·S area under the curve [AUC] .844 vs. rKtrans AUC .753, z = 2.064, p = .039; rE AUC .907 vs. rKtrans AUC .753, z = 2.399, p = .017). CONCLUSIONS: Patients with parenchymal hematoma after mechanical thrombectomy had higher blood-brain barrier permeability in hypoperfusion areas. Among blood-brain barrier permeability measurement parameters, rP·S and rE showed better accuracy for parenchymal hematoma prediction.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Barrera Hematoencefálica/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Accidente Cerebrovascular Isquémico/complicaciones , Trombectomía/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Hematoma/diagnóstico por imagen , Hematoma/cirugía , Infarto/complicaciones , Permeabilidad , Isquemia Encefálica/cirugía , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840-0.942), the Hosmer-Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.
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Edema Encefálico , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Nomogramas , Trombectomía , Humanos , Masculino , Femenino , Trombectomía/efectos adversos , Trombectomía/métodos , Anciano , Edema Encefálico/etiología , Edema Encefálico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Persona de Mediana Edad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Factores de Riesgo , Curva ROC , Anciano de 80 o más Años , Tomografía Computarizada por Rayos XRESUMEN
Plasmalogens (Pls) are considered to play a potential role in the treatment of neurodegenerative diseases. In the present study, an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 was established to investigate whether the marine-derived Pls could alleviate cognitive impairments of AD zebrafish. Behavioral tests were carried out to assess the athletic ability. The transcriptional profiles of zebrafish in the control, AD model and AD_PLS group were compared and analyzed to determine the potential mechanisms of dietary Pls on AD. The study found that Pls could reverse athletic impairment in the AD zebrafish model, and the expression levels of genes related to ferroptosis, synaptic dysfunction and apoptosis were significantly altered between experimental groups. Further analysis showed that all of these genes were associated with oxidative stress (OS). These data suggest that healthy protective role of marine-derived Pls on AD zebrafish may result from inhibition of ferroptosis and neuronal apoptosis, restoring synaptic neurotransmission release, and reducing neuroinflammation. Among them, Oxidative stress is acted as the center to connect different regulation pathways. This study provides evidence to support the essential roles of OS in pathogenesis of AD, and the application of Pls in relieving AD.
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Enfermedad de Alzheimer , Ferroptosis , Fármacos Neuroprotectores , Animales , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Pez Cebra/metabolismo , Plasmalógenos/metabolismo , Plasmalógenos/farmacología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Apoptosis , Transmisión SinápticaRESUMEN
Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1α, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca2+/CaMKII activation and Drp1/ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1α and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.
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Nanopartículas del Metal , Enfermedades Mitocondriales , Humanos , Plata/toxicidad , Plata/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Mitocondrias/metabolismo , Nanopartículas del Metal/toxicidadRESUMEN
Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.
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A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.
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Astrocitos , Compuestos de Bencidrilo , Dieta Alta en Grasa , Microbioma Gastrointestinal , Glucósidos , Enfermedades Neuroinflamatorias , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Astrocitos/efectos de los fármacos , Glucósidos/farmacología , Ratones , Compuestos de Bencidrilo/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Masculino , Ratones Endogámicos C57BL , Encéfalo/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , DisbiosisRESUMEN
Plasmalogens (Pls), a special group of phospholipids, are effective in ameliorating neurodegenerative disease. In the present study, the metabolic effects of seafood-derived Pls on high fat diet (HFD)-induced hyperlipidemia in zebrafish were evaluated, and the underlying mechanisms of dietary Pls against hyperlipidemia were explored through integrated analyses of hepatic transcriptomics and metabolomics. The results demonstrated that Pls supplementation could effectively alleviate HFD-induced obesity symptoms, such as body weight gain, and decrease total hepatic cholesterol and triglyceride levels. Integrated hepatic transcriptome and metabolome data suggested that Pls mainly altered lipid metabolism pathways (FA metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerolipid and glycerophospholipid metabolism) and the TCA cycle, induced the overexpression of anti-oxidation enzymes (Cat, Gpx4, Sod3a and Xdh), reduced disease biomarkers (such as glutarylcarnitine, gamma-glutamyltyrosine, and 11-prostaglandin f2) and gut microbiota-derived metabolites, and increased (±)12(13)-diHOME, EPA, lysoPC and PC levels. Moreover, 5 abnormally regulated metabolites were identified as potential biomarkers associated with hyperlipidemia according to the metabolomics results and suggested the involvement of gut microbiota in the anti-hyperlipidemic effects of Pls. Collectively, these findings suggest that the protective role of Pls is mainly associated with the promotion of unsaturated fatty acid biosynthesis and cholesterol efflux, lipid and phospholipid PUFA remodeling, and anti-oxidation and anti-inflammatory capabilities. This study provides valuable information for reasonably explaining the beneficial effects of seafood-derived Pls in alleviating hyperlipidemia and thus may contribute to the development and application of Pls as functional foods or dietary supplements to protect against obesity and hyperlipidemia.
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Hiperlipidemias , Enfermedades Neurodegenerativas , Animales , Ratones , Hiperlipidemias/etiología , Hiperlipidemias/genética , Pez Cebra/metabolismo , Dieta Alta en Grasa/efectos adversos , Plasmalógenos/farmacología , Transcriptoma , Enfermedades Neurodegenerativas/metabolismo , Metabolómica/métodos , Hígado/metabolismo , Obesidad/etiología , Obesidad/genética , Metabolismo de los Lípidos , Colesterol/metabolismo , Biomarcadores/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager. Herein we report such a case. CASE SUMMARY: A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo. Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12. Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes. Computed tomography angiography (CTA) indicated M3 segment embolism of the right middle cerebral artery. Neck CTA revealed thrombosis of the bilateral common carotid arteries. Carotid ultrasound showed thrombosis in the bilateral common carotid arteries (approximately 2 cm below the proximal end of the carotid sinus), and contrast-enhanced ultrasound did not suggest enhancement. No hypertension, diabetes, heart disease, vasculitis, or thrombophilia was found after admission. After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg, a carotid ultrasound reexamination showed that the thrombosis had significantly reduced. CONCLUSION: Neck massager may cause carotid artery thrombosis.
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BACKGROUND: Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. METHODS: The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. RESULTS: The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aß via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca2+, and PI3K/Akt signaling. ICA exhibits neuroprotective properties by inhibiting neuronal apoptosis through the suppression of ER stress in AD mice, potentially linked to NF-κB, MAPK, ERK, and PERK/Eif2α signaling pathways. Moreover, ICA may safeguard neurons by attenuating mitochondrial oxidative stress injury. ICA can also enhance learning, memory, and cognition by improving synaptic structure via regulation of the PSD-95 protein. Furthermore, ICA can mitigate neuroinflammation by inactivating microglial activity through the upregulation of PPARγ, TAK1/IKK/NF-κB, and JNK/p38 MAPK signaling pathways. CONCLUSION: This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , FN-kappa B , Fosfatidilinositol 3-Quinasas , Flavonoides/farmacología , Flavonoides/uso terapéuticoRESUMEN
Background: Numerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR). Methods: Fourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR-Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses. Results: In MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701-1.089, p = 0.230], MR-Egger (OR: 0.944, 95% CI: 0.692-1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678-1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999-1.001, p = 0.683). Conclusion: Our findings reveal no significant causal association between circulating ADPN and AD risk.
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Introduction: It is well-documented that systemic lupus erythematosus (SLE) is associated with dementia. However, the genetic causality of this association remains unclear. Mendelian randomization (MR) was used to investigate the potential causal relationship between SLE and dementia risk in the current study. Methods: We selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from publicly available genome-wide association studies (GWAS). Summary level statistics were obtained from the dementia GWAS database. MR estimates were performed using the inverse variance weighted (IVW) method, MR-Egger method and weighted median (WM) method. Cochran's Q test, the intercept of MR-Egger, MR-Pleiotropy Residual Sum and Outlier method, leave-one-out analysis and funnel plot were applied for sensitivity analyses. Results: No significant causal association was found between SLE and any type of dementia, including Alzheimer's disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. These findings were robust across several sensitivity analyses. Conclusion: Overall, our findings do not support a causal association between SLE and dementia risk.
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Enfermedad de Alzheimer , Lupus Eritematoso Sistémico , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Causalidad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/genética , Enfermedad de Alzheimer/genéticaRESUMEN
Background: Acute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion. Methods: We retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated. Results: Among the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0-2 (48.8 vs. 52.3%, p = 0.76). Conclusions: Rescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.