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Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16- are positively correlated with the risk of epilepsy (p < 0.001, OR = 1.0826, 95% CI 1.0361-1.1312). Similarly, metabolites also exhibit a causal relationship with both immune cells (OR = 1.0438, 95% CI 1.0087-1.0801, p = 0.0140) and epilepsy (p = 0.0334, OR = 1.0897, 95% CI 1.0068-1.1795), and sensitivity analysis was conducted to further validate these relationships. Importantly, our intermediate MR results suggest that the metabolite Paraxanthine to linoleate (18:2n6) ratio may mediate the causal relationship between immune cell CD64 on CD14-CD16- and epilepsy, with a mediation effect of 5.05%. The results suggest the importance of specific immune cell levels and metabolites in understanding epilepsy's pathogenesis, which is significant for its prevention and treatment.
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Epilepsia , Análisis de la Aleatorización Mendeliana , Humanos , Epilepsia/genética , Epilepsia/metabolismo , Epilepsia/inmunología , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dingxian Pill (DXP), a famous traditional Chinese medicine prescription, and has been widely proven to have positive therapeutic effects on "Xianzheng" (the name of epilepsy in ancient China). However, the anti-epileptic molecular mechanisms of DXP are not yet fully understood and remain to be further investigated. AIM OF THE STUDY: To elucidate the molecular mechanism of DXP's improvement in epileptic neuronal loss, damage and apoptosis by regulating TNF-α/TNFR1 signaling pathway. MATERIALS AND METHODS: Sixty Kunming mice were randomly divided in 6 groups: control group (equal volume of normal saline), model group (180 mg kg-1 pilocarpine hydrochloride - used to establish the epilepsy animal model), carbamazepine group (30 mg kg-1), and low, medium, and high-dose Dingxian Pill groups (4.08, 8.16, and 16.32 g kg-1, respectively - oral administration once daily for 2 weeks). Successful establishment of the epileptic mouse model was monitored with electroencephalography. Pathological changes in hippocampal tissue were analyzed with hematoxylin-eosin staining. Hippocampal neuronal apoptosis was analyzed with TUNEL staining. TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein expression levels in hippocampal tissue were analyzed with real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blot, respectively. Cleaved caspase-8 protein levels in hippocampal tissue were measured with immunohistochemistry and Western blot. RESULTS: Compared to control, the model group showed an increase in continuous epileptic discharge waves on EEG, a damaged hippocampal neuron morphological structure, increased hippocampal neuronal apoptosis, and significantly increased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels, and increased caspase-8 cleavage (P < 0.05). Compared to the model group, the carbamazepine group as well as the low-, medium-, and high-dose Dingxian Pill groups showed decreased epileptic discharges on EEG, an obvious hippocampal neuron morphological structure restoration, varying degrees of attenuated hippocampal neuronal apoptosis, and significantly decreased TNF-α, TNFR1, TRADD, FADD, and caspase-8 mRNA and protein levels as well as decreased caspase-8 cleavage (P < 0.05). CONCLUSIONS: Dingxian Pill exerts an anti-epileptic effect through inhibition of TNF-α/TNFR1 signaling pathway-mediated apoptosis in hippocampal neurons.
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Anticonvulsivantes , Apoptosis , Medicamentos Herbarios Chinos , Epilepsia , Hipocampo , Neuronas , Receptores Tipo I de Factores de Necrosis Tumoral , Transducción de Señal , Factor de Necrosis Tumoral alfa , Animales , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Apoptosis/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Epilepsia/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Ratones , Anticonvulsivantes/farmacología , Pilocarpina/toxicidad , Modelos Animales de Enfermedad , Animales no ConsanguíneosRESUMEN
Recent studies evidenced the involvement of circular RNA (circRNA) in neuroinflammation, apoptosis, and synaptic remodeling suggesting an important role for circRNA in the occurrence and development of epilepsy. This review provides an overview of circRNAs considered to be playing regulatory roles in the process of epilepsy and to be involved in multiple biological epilepsy-related processes, such as hippocampal sclerosis, inflammatory response, cell apoptosis, synaptic remodeling, and cell proliferation and differentiation. This review covers the current research status of differential expression of circRNA-mediated seizures, m6A methylation, demethylation-mediated seizures in post transcriptional circRNA modification, as well as the mechanisms of m5C- and m7G-modified circRNA. In summary, this article reviews the research progress on the relationship between circRNA in non-coding RNA and epilepsy.
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Epilepsia , ARN Circular , ARN Circular/metabolismo , ARN Circular/genética , Epilepsia/genética , Epilepsia/metabolismo , Humanos , AnimalesRESUMEN
Background: Epilepsy's pathogenesis and progression are significantly influenced by neuroinflammation, blood-brain barrier function, and synaptic remodeling function. Matrix metalloproteinase 9 (MMP-9), as a critical factor, may contribute to the development of epilepsy through one or more of the above-mentioned pathways. This study aims to evaluate and quantify the correlation between MMP-9 levels and epilepsy. Methods: We conducted a comprehensive search of Embase, Web of Science, PubMed, Cochrane Library, WanFang DATA, VIP, and the CNKI to identify studies that investigate the potential association between MMP-9 and epilepsy. The data were independently extracted by two researchers and assessed for quality using the Cochrane Collaboration tool. The extracted data were analyzed using Stata 15 and Review Manager 5.4. The study protocol was registered prospectively at PROSPERO, ID: CRD42023468493. Results: Thirteen studies with a total of 756 patients and 611 matched controls met the inclusion criteria. Eight of these studies reported total serum MMP-9 levels, and the other five studies were used for a further subgroup analysis. The meta-analysis indicated that the serum MMP-9 level was higher in epilepsy patients (SMD = 4.18, 95% confidence interval = 2.18-6.17, p < 0.00001) compared with that in the control group. Publication bias was not detected according to Begg's test. The subgroup analysis of country indicated that the epilepsy patients in China, Poland, and Egypt had higher levels of serum MMP-9 than the control group, with the increase being more pronounced in Egypt. The subgroup analysis of the age category demonstrated that the serum MMP-9 levels of the adult patients with epilepsy were significantly higher than those of the matched controls. However, the serum MMP-9 levels did not significantly differ in children with epilepsy. The subgroup analysis of the seizure types demonstrated substantial difference in the MMP-9 levels between patients of seizure-free epilepsy (patients who have been seizure-free for at least 7 days) and the control group. Meanwhile, the serum MMP-9 level in patients with epileptic seizures was significantly higher than that in the control group. The subgroup analysis based on seizure duration in patients showed that the serum MMP-9 levels at 1-3, 24, and 72 h after seizure did not exhibit significant differences between female and male patients with epilepsy when compared with the control group. The serum MMP-9 levels at 1-3 and 24 h were significantly higher than those of the matched controls. Nevertheless, the serum MMP-9 level at 72 h was not significantly different from that in the control group. Conclusion: This meta-analysis presents the first comprehensive summary of the connection between serum MMP-9 level and epilepsy. The MMP-9 levels in epilepsy patients are elevated. Large-scale studies with a high level of evidence are necessary to determine the exact relationship between MMP-9 and epilepsy.
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Prior studies have revealed an increased susceptibility to epilepsy in hyperthyroid individuals, but the genetic basis of the hyperthyroidism-epilepsy relationship is not fully comprehended, prompting this study to explore this potential association. We conducted a two-sample Mendelian randomization (TSMR) study to explore the relationship between hyperthyroidism and epilepsy by utilizing aggregated statistics from Genome-Wide Association Studies (GWAS). Data for hyperthyroidism were derived from a GWAS encompassing 462,933 participants, while epilepsy data were sourced from the International League Against Epilepsy (ILAE) consortium. Five distinct methods were employed for TSMR analysis, which included the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In our sensitivity analysis, we employed the MR Egger and MR PRESSO methods to assess pleiotropy, and inverse variance weighting and MR Egger in Cochran's Q statistics to assess heterogeneity. In the IEU database, utilizing the MR-Egger method, we obtained an odds ratio (OR) of 2.631 (95% CI 0.608, 9.796) with a p-value of 0.122. Meanwhile, employing the Weighted Median method yielded an OR of 1.813 (95% CI 0.786, 4.181) with a p-value of 0.163. The IVW method exhibited an OR of 1.986 (95% CI 1.127, 3.502) with a p-value of 0.018. In the assessment of heterogeneity, the MR-Egger method produced a Q statistic of 65.205, accompanied by a p-value of 0.087, while the IVW method recorded a Q statistic of 66.668 with a p-value of 0.083. The multifactorial analysis results showed an intercept term with a standard error (SE) value of 0.009 and a p-value of 0.291. In the FinnGen database, employing the MR-Egger method for all epilepsy data, we observed an OR of 0.952 (95% CI 0.831, 1.093) with a p-value of 0.539. Simultaneously, the Weighted Median method produced an OR of 0.986 (95% CI 0.953, 1.021) with a p-value of 0.423. The IVW method indicated an OR of 0.992 (95% CI 0.965, 1.019) with a p-value of 0.541. The MR-Egger method's assessment of heterogeneity resulted in a Q statistic of 2.671, associated with a p-value of 0.445, while the IVW method generated a Q statistic of 3.011 with a p-value of 0.556. The multifactorial analysis results displayed an intercept term with a SE-value of 0.019 and a p-value of 0.601. Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Hyperthyroidism was found to be causally related to all epilepsy but had no effect on other types of epilepsy.
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Epilepsia , Hipertiroidismo , Humanos , Epilepsia/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización MendelianaRESUMEN
OBJECTIVE: To explore gut microbiota changes in intractable epilepsy patients compared to healthy control individuals through meta-analysis. METHODS: PubMed, Web of Science, CNKI, Wanfang, medRxiv, bioRxiv, ilae.org, clinical trial databases, and papers from the International Epilepsy Congress (IEC) were searched, and the literature on the correlation between intractable epilepsy and the gut microbiota reported from database establishment to June 2023 was included. Literature meeting the inclusion criteria was screened, and meta-analysis of the included literature was performed using RevMan5.4 software. RESULTS: Ten case-control studies were included in the meta-analysis. There were 183 patients with intractable epilepsy and 283 healthy control subjects. The analysis results indicated that Bacteroidetes (MD = -0.64, 95 %-CI = -1.21 to -0.06) and Ruminococcaceae (MD = -1.44, 95 % CI = -1.96 to -0.92) were less abundant in the patients with intractable epilepsy than in the normal population. Proteobacteria (MD = 0.53, 95 % CI = 0.02 to 1.05) and Verrucomicrobia (MD = 0.26, 95 % CI = 0.06 to 0.45) were more abundant in the patients with intractable epilepsy than in the normal population. CONCLUSION: This meta-analysis indicated that the abundances of Bacteroidetes and Ruminococcaceae were reduced while those of Proteobacteria and Verrucomicrobia were significantly increased in patients with intractable epilepsy. The above changes in these four taxa of the gut microbiota may have been induced by intractable epilepsy, which may increase the risk of seizures. Their roles in the pathogenesis of intractable epilepsy need to be further explored, and related factors that influence microbiota changes should be considered in future studies.
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Epilepsia Refractaria , Microbioma Gastrointestinal , Humanos , Convulsiones , Estudios de Casos y Controles , Bases de Datos FactualesRESUMEN
Inflammatory myofibroblastic tumors (IMTs) are rare lesions with distinct clinical, pathological, and molecular characteristics. IMTs typically arise in the abdominal soft tissues, including the mesentery, omentum, and retroperitoneum, followed by the lungs and mediastinum, and usually affect both children and young adults. Herein, we present a rare case of an IMT in the submandibular gland of a 47-year-old male patient. Microscopically, the tumor displayed an infiltrative growth pattern with diffuse glandular tissue destruction. Their backgrounds revealed characteristic spindles and inflammatory cells. Immunohistochemistry revealed positivity for anaplastic lymphoma kinase (ALK), smooth muscle actin, and calponin in neoplastic cells. The inflammatory cells and some neoplastic cells were positive for CD68. In contrast, negative staining for cytokeratin, desmin, and CD30 was observed. Furthermore, fluorescence in situ hybridization revealed ALK gene rearrangements, and next-generation sequencing detected a moesin (MSN)-ALK gene fusion. This case highlights a rare and unique occurrence of IMT originating from the submandibular gland, which exhibited an MSN-ALK gene fusion.
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BACKGROUND: Studies have shown conflicting results in the correlation between serotonin-1A (5-HT1A) receptor binding levels in the brain and temporal lobe epilepsy (TLE). There is a need to systematically evaluate the correlation between the 5-HT1A binding level and TLE from the perspective of the brain using molecular imaging. METHODS: Chinese and English databases, such as the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal Database (VIP), WanFang, the Chinese Biomedical Literature Service System (SinoMed), PubMed and Web of Science, were searched. RESULTS: Two evaluators independently screened the literature, extracted data, and evaluated the risk of bias in the included studies according to the inclusion and exclusion criteria. RevMan 5.4.1 was used to analyze the data. A total of 196 participants were included; of these, 95 had TLE and 131 were healthy controls who had never had a seizure before participating in the study. Meta-analysis results suggested that 1) decreased 5-HT1A binding was found on the affected side of patients with TLE (standard mean difference (SMD) = -1.45, 95% confidence interval (CI) [-2.27, -0.64], Z = 3.48, P = 0.0005); 2) decreased 5-HT1A binding was found in the ipsilateral hippocampus of patients with TLE (SMD = -1.76, 95% CI [-2.51, -1.00], Z = 4.57, Pï¼0.00001); 3) decreased 5-HT1A binding was found in the ipsilateral temporal lobe cortex of patients with TLE (SMD = -0.46, 95% CI [-0.80, -0.12], Z = 2.66, P = 0.008); 4) decreased 5-HT1A binding was found in the ipsilateral amygdala in patients with TLE (SMD = -1.36, 95% CI [-2.48, -0.23], Z = 2.37, P = 0.02); and 5) decreased 5-HT1A binding was found in the frontal lobe of patients with TLE(SMD = -0.75, 95% CI [-1.29, -0.20], Z = 2.67, P = 0.008). CONCLUSION: A reduction in 5-HT1A binding in the hippocampus, temporal cortex, amygdala, and frontal lobe was observed on the affected side of patients with TLE. The decrease in 5-HT1A binding can be considered related to TLE. Potentially relevant factors should be considered in future molecular imaging studies.
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Epilepsia del Lóbulo Temporal , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Imagen por Resonancia Magnética/métodos , Convulsiones/metabolismo , Lóbulo Temporal/metabolismoRESUMEN
BACKGROUND: The related factors affecting the adherence of ischemic cerebral stroke (ICS) patients to antiplatelet therapy have attracted much attention. METHODS: Patients with ICS (confirmed by CT or MRI) were enrolled from January 2020 to July 2021. The demographic data were retrospectively investigated and analyzed. The adherence calculation was as follows: Adherence = number of tablets taken/number of tablets needed to be taken. Adherence < 100% was defined as nonadherence. Severe nonadherence is defined as adherence ≤ 75%. RESULTS: A total of 229 patients with ICS were enrolled. We found no significant difference in the proportion of patients with nonadherence, while the proportion of severe nonadherence in the aspirin group was significantly higher (p < .001). Multivariable analysis indicated that medical insurance (odds ratio [OR] = 0.071, p < .001) and regular exercise (OR = 0.438, p = .015) were independent factors associated with adherence. In addition, only medical insurance (OR = 5.475, p < .001) and aspirin treatment (OR = 0.228, p < .001) were independent risk factors associated with severe nonadherence. We therefore constructed a nomogram plot and a model as follows: Adherence risk score = 3 × medical insurance + regular exercise. Patients were divided into low-risk and high-risk groups for adherence based on the median model score. A total of 13.3% of patients in the low-risk group were nonadherent patients compared with 53.4% in the high-risk group (p < .001). Similarly, 8.4% of patients in the low-risk group had severe nonadherence compared with 19.9% in the high-risk group (p = .022). Moreover, in low-risk patients, no significant difference was observed. In patients with high risk, aspirin-treated patients showed significantly decreased adherence compared with the other two groups. CONCLUSION: Medical insurance and regular exercise were independent factors for antiplatelet therapy adherence. For patients with high model scores, timely intervention is necessary.
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Accidente Cerebrovascular Isquémico , Enfermedades del Sistema Nervioso , Accidente Cerebrovascular , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Aspirina/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Cumplimiento de la MedicaciónRESUMEN
Epilepsy is a clinical syndrome caused by the highly synchronized abnormal discharge of brain neurons. It has the characteristics of paroxysmal, transient, repetitive, and stereotyped. Circular RNAs (circRNAs) are a recently discovered type of noncoding RNA with diverse cellular functions related to their excellent stability; additionally, some circRNAs can bind and regulate microRNAs (miRNAs). The present study was designed to screen the differentially expressed circRNA in an acute seizure model of epilepsy in mice, analyze the related miRNA and mRNA, and study their participating functions and enrichment pathways. In order to obtain the differential expression of circRNA in epilepsy and infer their function, we used next-generation sequencing and found significantly different transcripts. CIRI (circRNA identifier) software was used to predict circRNA from the hippocampus cDNA, EdgeR was applied for the differential circRNA analysis between samples, and Cytoscape 3.7.2 software was used to draw the network diagram. A total of 10,388 differentially expressed circRNAs were identified, of which 34 were upregulated and 66 were downregulated. Among them, mm9_circ_008777 and mm9_circ_004424 were the key upregulated genes, and their expression in the epilepsy group was verified using Quantitative real-time PCR (QPCR). The analysis indicated that the extracted gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were closely related to several epilepsy-associated processes. This study determined that mm9_circ_008777 and mm9_circ_004424 are potential biomarkers of epilepsy, which play important roles in epilepsy-related pathways. These results could help improve the understanding of the biological mechanisms of circRNAs and epilepsy treatments.
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Epilepsia/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Hipocampo/patología , ARN Circular/genética , Animales , RatonesRESUMEN
Temporal lobe epilepsy (TLE) is a chronic disease of the nervous system, associated with increased proliferation in the hippocampus. Urothcarcinoma associated 1 (UCA1) is a long long non-coding RNA that was shown to regulate proliferation and differentiation of neural progenitors in vitro. We hypothesised that TLE-associated abnormal proliferation is a consequence of the downregulation of UCA1. This hypothesis was tested in mice with kainic acid (KA)-induced seizures, and then the potential mechanism was explored in vitro and in vivo. Result showed that the expression of UCA1 and Secreted Frizzled Related Protein 1 (SFRP1) were significantly reduced in hippocampal tissues of epileptic mice, while miR-375 was increased compared with the control group. Pearson correlation analysis showed that UCA1 was positively correlated with SFRP1, while miR-375 was negatively correlated with UCA1 and SFRP1. Besides, UCA1 was overexpressed in mice and the overexpression of UCA1 significantly reversed the abnormal proliferation of hippocampal neurons in epilepsy mice. In vitro Luciferase assay showed that UCA1 and Sfrp1 are both the targets of miR-375, and UCA1 promotes the expression of Sfrp1 by competitively adsorbing miR-375, thereby inhibiting the activation of the WNT/ß-catenin pathway. The inactivation of the WNT/ß-catenin pathway prevented the abnormal proliferation of neural progenitors in the epileptic hippocampus. In conclusion, our findings provide a theoretical basis for the clinical application of UCA1.
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Epilepsia/genética , Hipocampo/efectos de los fármacos , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Neurogénesis/efectos de los fármacos , ARN Largo no Codificante/genética , Vía de Señalización Wnt/efectos de los fármacos , Animales , Proliferación Celular/genética , Epilepsia/metabolismo , Vectores Genéticos/farmacología , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ácido Kaínico/efectos adversos , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Neurogénesis/genética , Vía de Señalización Wnt/genéticaRESUMEN
The aim of this study was to investigate the alterations in a verbal working memory (VWM)-related network in left temporal lobe epilepsy (lTLE) at rest. We evaluated 14 patients with lTLE and 14 control subjects by resting-state functional connectivity (RSFC). The region of interest was defined by the voxel with the highest Z-score during a VWM task according to functional magnetic resonance imaging in 16 healthy volunteers. Our study revealed that the network of RSFC was similar to the task-induced network in the healthy volunteers. Moreover, the patients with lTLE exhibited significantly decreased RSFC in the bilateral middle frontal gyrus, the inferior frontal gyrus and the inferior parietal lobule at rest compared to the control subjects. We found no significant correlation between the mean reaction time of the accurate responses in a 2-back task and the mean z-values within the regions that exhibited significant differences in RSFC at the individual level. The alterations in FCs of VWM-related network in lTLE suggested that epileptiform discharges can damage the brain regions, both local focus and remote areas and that the alterations were not associated with VWM performance.
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Encéfalo/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Memoria a Corto Plazo , Aprendizaje Verbal , Adulto , Mapeo Encefálico , Estudios de Casos y Controles , Epilepsia del Lóbulo Temporal/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
Chemokine receptors CXCR4 and CCR5 are indispensable co-receptors for HIV-1 entry into host cells. In our previous study, we identified that dopamine receptor-interacting protein 78 (DRiP78) and Na(+)-H(+) exchanger regulatory factor 1 (NHERF1) are the CXCR4 and CCR5 homo- or hetero-dimer-interacting proteins. DRiP78 and NHERF1 are able to influence the co-receptor internalization and intracellular trafficking. Over-expression of NHERF1 affects the ligands or HIV-1 gp120-induced CCR5 internalization and HIV-1 production. It is reasonable to speculate that DRiP78 and NHERF1, as well as the signaling pathways involved in viral replication, would probably affect HIV-1 replication through regulating the co-receptors. In this present study, we designed two short hairpin RNAs (shRNAs) targeting the DRiP78 and NHERF1, respectively, and constructed the pLenti6/BLOCK-iT-DEST lentiviral plasmids expressing DRiP78 or NHERF1 shRNA. The packaged lentiviruses were used to transduce the widely-applied HIV-1 model cell line GHOST(3). Then, cells with stable knockdown were established through selecting transduced cells with Blasticidin. This study, for the first time, reported the establishment of the GHOST(3) with DRiP78 and NHERF1 knockdown, which is the first stable cell line with HIV-1 co-receptor-interacting molecular defects.
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Línea Celular , Proteínas Fetales/genética , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/fisiología , Chaperonas Moleculares/genética , Fosfoproteínas/genética , Intercambiadores de Sodio-Hidrógeno/genética , Línea Celular/metabolismo , Línea Celular/virología , Proteínas Fetales/metabolismo , Técnicas de Silenciamiento del Gen , Infecciones por VIH/metabolismo , VIH-1/genética , Humanos , Chaperonas Moleculares/metabolismo , Fosfoproteínas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Replicación ViralRESUMEN
OBJECTIVE: To evaluate executive deficits in patients with left temporal lobe epilepsy (TLE) and to analyze the association of executive deficits and diffusion tensor imaging (DTI) parameters of the uncinate fasciculus. METHODS: This study included 14 adult left TLE patients and 15 healthy controls. Executive function was examined using neuropsychological tests, including the Stroop color-word, digit span, digit symbol, trail-making test, and verbal fluency tests. All subjects underwent brain DTI. RESULTS: Compared with controls, TLE patients needed significantly more time (P=0.036) and had more wrong answers (P<0.001) in the Stroop test, and exhibited significantly lower scores in the digit span (P=0.017), digit symbol (P=0.009), and verbal fluency (P=0.001) tests. Additionally, TLE patients took significantly longer to accomplish the trail-making test (P=0.042). Fractional anisotropy (FA) of the left uncinate fasciculus in TLE patients was significantly lower compared to controls (P<0.001). FA of the left uncinate fasciculus in TLE patients and controls positively correlated with verbal fluency (r=0.565, P=0.035; r=0.561, P=0.031) and digit span (r=0.556, P=0.039; r=0.559, P=0.030) test scores. CONCLUSIONS: Patients with left TLE exhibit wide ranges of executive deficits. Abnormal FA values in the left UF ipsilateral to the epileptogenic zone suggest that disrupted integrity in the left uncinate fasciculus is related to executive deficits in patients with left TLE.
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Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/patología , Imagen de Difusión Tensora , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/patología , Sustancia Blanca/patología , Adolescente , Adulto , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
OBJECTIVE: To study the structural integrity and continuity of the bilateral uncinate fasciculus (UF) in patients with temporal lobe epilepsy (TLE) using magnetic resonance diffusion tensor imaging (DTI) and evaluate the impact of structural damage of the UF on the executive function of the patients. METHODS: Thirty patients with TLE (14 left, 16 right) and 15 healthy control subjects underwent DTI scanning between January, 2007 and July, 2011, and the left and right UF were analyzed for fractional anisotropy (FA) and fiber mean length. RESULTS: In the control subjects, the average FA was significantly higher in the left than in the right UF (P<0.01). In patients with left TLE, the average FA of the left UF was significantly lower than that of the control subjects (P<0.01), but the FA of the right UF was comparable with that of the control group (P>0.05). In patients with right TLE, the average FA of the left and right UF was significantly lower than that of the control group (P<0.05 and P<0.01). In patients with unilateral TLE, the FA of their bilateral UF was similar. No significant difference was found in the mean length of UF fiber between these 3 groups. CONCLUSIONS: FA is normally higher in the left UF than in the right UF, but inpatients with TLE, the left FA tends to have a lowered UF regardless of which hemisphere is involved, suggesting an early pathology in the microstructure of the left UF. This finding may help in the investigation of possible reasons for executive function damage in TLE patients.
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Imagen de Difusión Tensora , Epilepsia del Lóbulo Temporal/patología , Estudios de Casos y Controles , Femenino , Humanos , MasculinoRESUMEN
To study genetic diversity and drug resistance of HIV-1 CRF_BC among drug users in Guangdong Province, 67 circulating recombinant form 07_BC (CRF_07BC) and 32 circulating recombinant form 08_BC(CRF_08BC) HIV-1 pol genes were amplified and sequenced. In the protease gene region (PR), 31 CRF_08BC isolates were amplified and 10 high polymorphism positions were identified. The polymorphisms L19I, M36I, R41K, D60E, L63P, H69K, and I93L were complete substitutions, and were followed by T12S (94%), I15V (90%), and L89M (81%) separately. Five high polymorphisms were found in CRF_07BC isolates; there were E35D (88%), R41K (100%), D60E (96%), L63P (99%), and I93L (91%). Four of the identified polymorphism positions (R41K, D60E, L63P, and I93L) were the same in the PR region of both subtypes. In the reverse transcriptase (RT) region six high polymorphism positions, V35T, E36A, T39D/E/N, S48T, V60I, and V245Q, were identified in both subtypes. E53D (97%), I135V/T/R (81%), S162C (94%), Q207E (100%), and R211K (97%) were primarily in CRF_08BC subtypes and D121Y/H (97%) were primarily in CRF_07BC. The NRTI resistance mutation T69S was 94% (30/32) in CRF_08BC. To now, we have found no related reports concerning such high polymorphisms in the position. Polymorphisms V77M (PI) and K201Q (RT) were not found in the mutation profiles; therefore it may have been a new mutation in HIV-1. This study analyzed the difference between CRF_08BC and 07BC polymorphisms among drug users in Guangdong Province, which may help to guide recommendations for diagnostic assays, vaccine design, and antiretroviral regimen strategies in China.
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Farmacorresistencia Viral , Consumidores de Drogas , Variación Genética , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/genética , Mutación Missense , Adulto , Sustitución de Aminoácidos/genética , China/epidemiología , Análisis por Conglomerados , Femenino , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Homología de Secuencia , Adulto Joven , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
Sentinel surveillance data from 1995 to 2005 for drug users in Guangdong province, China, showed an increasing prevalence of HIV in the West region while stabilizing in the East and Center. Several factors were significantly associated with HIV infection including gender, age, sharing needles, years injecting, engaging in commercial sex, and being part of the migrant population of Guangdong. Data help effectively prioritize and target HIV prevention efforts for drug users.
Asunto(s)
Infecciones por VIH/epidemiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , China/epidemiología , Emigración e Inmigración , Femenino , Infecciones por VIH/transmisión , Humanos , Masculino , Compartición de Agujas , Prevalencia , Asunción de Riesgos , Vigilancia de Guardia , Conducta Sexual , Abuso de Sustancias por Vía Intravenosa/epidemiologíaRESUMEN
OBJECTIVE: To investigate subtype and genetic analysis of human immunodeficiency virus type-1 (HIV-1). METHODS: DNA sequences were amplified by nested-PCR from uncultured peripheral blood mononuclear cells (PBMC) obtained from 100 HIV-1 patients from Guangdong Province. The C2 to V3 region of the envelope glycoprotein gp120 of HIV-1 was sequenced directly. The analysis of the gene-based phylogenetic tree and variation of amino acid were carried out by using Wisconsin software package or genetics computer group (GCG). RESULTS: DNA fragments were amplified from 75 PBMC samples by using nested polymerase chain reaction (PCR). Sequence analysis showed that there were 3 HIV-1 subtypes or circulating recombinant forms (CRF): CRF01-AE (n = 44), CRF-BC (n = 27) and B' (n = 4). CONCLUSIONS: Three HIV-1 subtypes or circulating recombinant forms: CRF01-AE, CRF-BC and B' might be circulating in Guangdong Province. Findings from this study suggested that several subtypes might exist in Guangdong Province and the epidemic situation of AIDS be serious. It should be a challenge for Guangdong Province in treating patients, preventing and controlling AIDS in the future.