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1.
Ann Neurol ; 95(5): 901-906, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38400794

RESUMEN

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.


Asunto(s)
Astrocitos , Proteína Ácida Fibrilar de la Glía , Antígenos HLA-A , Cadenas beta de HLA-DP , Humanos , Proteína Ácida Fibrilar de la Glía/genética , Masculino , Femenino , Persona de Mediana Edad , Cadenas beta de HLA-DP/genética , Adulto , Antígenos HLA-A/genética , Astrocitos/metabolismo , Astrocitos/patología , Anciano
2.
J Neurol Neurosurg Psychiatry ; 94(8): 605-613, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37225405

RESUMEN

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.


Asunto(s)
Encefalitis , Infecciones por Virus de Epstein-Barr , Masculino , Humanos , Femenino , Autoinmunidad , Estudios Retrospectivos , Herpesvirus Humano 4 , Autoanticuerpos , Inmunoglobulina G
3.
Eur J Clin Microbiol Infect Dis ; 42(10): 1183-1194, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37606868

RESUMEN

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.


Asunto(s)
Cryptococcus , Infecciones por VIH , Meningitis Criptocócica , Humanos , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Inteligencia Artificial , Pronóstico , Aprendizaje Automático , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico
4.
Int J Mol Sci ; 24(10)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37240097

RESUMEN

The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the GC fate is regulated are unknown in Guanzhong dairy goats. Therefore, we investigated miR-486 expression in small and large follicles, as well as its impact on normal GC survival, apoptosis and autophagy in vitro. Here, we identified and characterized miR-486 interaction with Ser/Arg-rich splicing factor 3 (SRSF3) using luciferase reporter analysis, detecting its role in GC survival, apoptosis and autophagy regulation through qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, mitochondrial membrane potential and monodansylcadaverine, etc. Our findings revealed prominent effects of miR-486 in the regulation of GC survival, apoptosis and autophagy by targeting SRSF3, which might explain the high differential expression of miR-486 in the ovaries of monotocous dairy goats. In summary, this study aimed to reveal the underlying molecular mechanism of miR-486 regulation on GC function and its effect on ovarian follicle atresia in dairy goats, as well as the functional interpretation of the downstream target gene SRSF3.


Asunto(s)
Atresia Folicular , MicroARNs , Animales , Femenino , Atresia Folicular/genética , Células de la Granulosa/metabolismo , MicroARNs/metabolismo , Apoptosis/genética , Cabras/fisiología , Autofagia/genética
5.
Mov Disord ; 37(3): 545-552, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34820915

RESUMEN

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.


Asunto(s)
Corea , Distonía , Proteínas de la Membrana , Adolescente , Niño , Femenino , Humanos , Masculino , Corea/genética , Distonía/genética , Proteínas de la Membrana/metabolismo , Mutación/genética , Fenotipo
6.
Gen Comp Endocrinol ; 321-322: 114027, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35300988

RESUMEN

Paired-like homeodomain transcription factor 2 (PITX2), a major driver of multiple tissue development, is a transcription factor that regulates gene expression in organisms. However, it is unknown if PITX2 regulates goat granulosa cell (GC) steroidogenesis. Therefore, we investigated the role and mechanism of PITX2 in GC steroidogenesis. In our study, PITX2 significantly facilitated the secretion level of estrogen and progesterone through increasing CYP11A1, CYP19A1, and STAR mRNA and protein expressions in GCs. Furthermore, PITX2 participated in the WNT pathway, enhancing the production of E2 and P4 in GCs. PITX2 in GCs increased the DVL-1 and CTNNB1 expression, involved in the WNT/ß-catenin signaling pathway related to steroidogenesis. Moreover, GC steroidogenesis-related gene translation was decreased by CTNNB1-siRNA but enhanced when transfected with PITX2. PITX2 regulates secretion of E2 and P4 from GCs via the WNT/ß-catenin pathway and alters GC proliferation and steroidogenesis. These findings will help understand the role of PITX2 in goat ovarian follicular development and oocyte maturation.


Asunto(s)
Vía de Señalización Wnt , beta Catenina , Animales , Femenino , Cabras/metabolismo , Células de la Granulosa/metabolismo , Factores de Transcripción/genética , beta Catenina/genética , beta Catenina/metabolismo
7.
Cytokine ; 111: 140-145, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30142535

RESUMEN

Syndecan-1 (SDC-1) is a transmembrane member that has a profound influence on the resolution of inflammation. Soluble syndecan-1 (sSDC-1) levels have been shown to increase in many inflammatory diseases. However, it remains unknown whether sSDC-1 concentration is elevated in neuromyelitis optica (NMO) and multiple sclerosis (MS) patients. The aims of this pilot study were to investigate the relationship between sSDC-1 and disease severity in NMO and MS and whether sSDC-1 has potential as an effective marker for disease severity. We measured sSDC-1 concentrations by using an enzyme-linked immunosorbent assay (ELISA). NMO patients had significantly higher CSF sSDC-1 levels than MS patients or controls. We also found a positive correlation between the increased CSF sSDC-1 levels and increased severity in NMO disease, but not in MS. In NMO, CSF sSDC-1 concentrations were positively correlated with CSF interleukin (IL)-6, IL-8 and IL-17. Overall, we showed levels of CSF sSDC-1 were higher in NMO patients and had a positive relationship with disease severity of NMO but not with MS. CSF sSDC-1 may be an effective marker of NMO disease severity.


Asunto(s)
Neuromielitis Óptica , Índice de Severidad de la Enfermedad , Sindecano-1 , Adolescente , Adulto , Citocinas/sangre , Citocinas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/patología , Solubilidad , Sindecano-1/sangre , Sindecano-1/inmunología
8.
Neurol Sci ; 39(1): 71-77, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29027029

RESUMEN

The objective of the study is to evaluate postural dysfunction of multiple system atrophy-parkinsonian type (MSA-P) and cerebellar type (MSA-C) by static posturography exam. A total of 29 MSA-P patients, 40 MSA-C patients, and 23 healthy controls (HC) were recruited and engaged in a sensory organization test (SOT). The amplitude of the postural sway was measured and transformed into energy value by Fourier analyzer. SOT scores, frequency of falls and typical 3-Hz postural tremors during the four stance tasks, and energy value in three different frequency bands were recorded and compared. Compared with HC, SOT scores were significantly lower in MSA groups (P < 0.01). Compared with MSA-P, the vestibular scores were further reduced in MSA-C patients (P < 0.05). Falls were more frequent in MSA groups, especially in SOT4 task (foam surface with eyes closed) or in MSA-C group (P < 0.05). Typical 3-Hz postural tremor was observed in 97.5% MSA-C patients, in 24.1% MSA-P patients but in none of the HC (P < 0.05). Compared with HC, much more energy was consumed in every task, every direction, and nearly every frequency band in MSA groups. Energy value of MSA-C group was significantly higher than that of MSA-P, especially in higher frequency band (2 ~ 20 Hz) or in more difficult stance tasks (SOT 3 ~ 4, foam surface with eyes open or closed) (P < 0.05). Both MSA-P and MSA-C were characterized by severe static postural dysfunction. However, typical 3-Hz postural tremor was predominant in MSA-C and was very useful in the differential diagnosis between MSA-P and MSA-C.


Asunto(s)
Enfermedades Cerebelosas/diagnóstico , Atrofia de Múltiples Sistemas/diagnóstico , Postura , Temblor/diagnóstico , Adulto , Anciano , Enfermedades Cerebelosas/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/complicaciones , Examen Neurológico , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/diagnóstico , Temblor/etiología , Pruebas de Función Vestibular
9.
Somatosens Mot Res ; 34(1): 15-20, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28114839

RESUMEN

BACKGROUND: Although hand motor cortex (HMC) has been constantly used for identification of primary motor cortex in magnetic resonance spectroscopy (MRS) studies of amyotrophic lateral sclerosis (ALS), neurochemical profiles of HMC have never been assessed independently. As HMC has a constant location and the clinic-anatomic correlation between hand motor function and HMC has been established, we hypothesize that HMC may serve as a promising region of interest in diagnosing ALS. PATIENTS AND METHODS: Fourteen ALS patients and 14 age- and gender-matched healthy controls (HC) were recruited in this study. An optimized magnetic resonance spectroscopic imaging (MRSI) method was developed and for each subject bilateral HMC areas were scanned separately (two-dimensional multi-voxel MRSI, voxel size 0.56 cm3). N-acetyl aspartate (NAA)-creatine (Cr) ratio was measured from HMC and the adjacent postcentral gyrus. RESULTS: Compared with HC, NAA/Cr ratios from HMC and the postcentral gyrus were significantly reduced in ALS. However, in each group the difference of NAA/Cr ratios between HMC and the postcentral gyrus was not significant. Limb predominance of HMC was not found in either ALS or HC. In ALS, there was a significant difference in NAA/Cr ratio between the most affected HMC and the less affected HMC. A positive relationship between NAA/Cr ratio of HMC and the severity of hand strength (assessed by finger tapping speed) was demonstrated. CONCLUSION: Neuronal dysfunction of HMC can differentiate ALS patients from HC when represented as reduced NAA/Cr ratio. Postcentral gyrus could not serve as normal internal reference tissue in diagnosing ALS. Asymmetrical NAA/Cr ratios from bilateral HMC may serve as a promising diagnostic biomarker of ALS at the individual level.


Asunto(s)
Esclerosis Amiotrófica Lateral/complicaciones , Ácido Aspártico/análogos & derivados , Mano/inervación , Espectroscopía de Resonancia Magnética , Corteza Motora/metabolismo , Adulto , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Creatina/metabolismo , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas
10.
Int J Neurosci ; 127(9): 790-799, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27838939

RESUMEN

BACKGROUND: Aquaporin-4 (AQP4) antibody sero-positivity is critically important in neuromyelitis optica (NMO). However, the sensitivity of different assays is highly variable. Repeating detection with a highly sensitive assay in a large population is necessary in the case of so-called negative NMO. METHODS: Retrospective analysis where AQP4 antibodies were detected by commercial cell-based assay (CBA), in-house M23-CBA and in-house M1-CBA. RESULTS: Of the 1011 serum samples, 206 (20.4%) were sero-positive by primary commercial CBA. In the retest, all 206 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA again, but only 124 positive in in-house M1-CBA. Among the 805 participants negative by primary commercial CBA, 71 participants were positive for in-house M23-CBA, of which 20 participants were positive for the second commercial CBA, and none were positive by in-house M1-CBA. Of the 171 cerebral spinal fluid samples, 75 (43.9%) were positive by primary commercial CBA. All 75 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA. Forty-nine (65.3%) of these 75 participants were positive by in-house M1-CBA. Among the 96 participants negative by primary commercial CBA, 15 participants were positive for in-house M23-CBA and none were positive by in-house M1-CBA and the second commercial CBA. CONCLUSIONS: Different AQP4 isoforms in CBA result in different detection effects, and in-house M23-CBA is the most sensitive method. Some AQP4 antibody-negative NMO may be subject to diagnostic uncertainty due to limitations of the assays.


Asunto(s)
Acuaporina 4/inmunología , Autoanticuerpos/sangre , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico , Adolescente , Adulto , Acuaporina 4/genética , Autoanticuerpos/líquido cefalorraquídeo , China/epidemiología , Femenino , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Estudios Retrospectivos , Estadísticas no Paramétricas , Transfección , Adulto Joven
11.
Bioresour Technol ; 394: 130210, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38113949

RESUMEN

Electrochemical sludge pretreatment is receiving increasing attention because of its small footprint and higher environmental compatibility. However, the limited effective area of electrode plates and the low conductivity of sludge hinder the widespread application of electrochemical pretreatment. In this study, granular activated carbon (GAC) was employed to construct a fluidized electrode electrochemical system (FEE) to promote electrochemical pretreatment. Under the optimal operating parameters, the FEE system could effectively facilitate sludge decomposition, indicated by 126% increase in soluble chemical oxygen demand (SCOD) and 23.1% reduction in sludge volume. Mechanism study revealed that the addition of GAC significantly enhanced the conductivity of sludge, thereby promoting the oxidation capacity of FEE system. Furthermore, continuously generated H2O2 in FEE further promoted sludge solubilization. GAC offered an effectively, green and sustainable enhancement approach for sludge electrochemical pretreatment.


Asunto(s)
Carbón Orgánico , Aguas del Alcantarillado , Peróxido de Hidrógeno , Reactores Biológicos , Electrodos
12.
Food Res Int ; 175: 113818, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129015

RESUMEN

Human and animal exposure to microplastics (MPs) contained in food is inevitable because of their widespread existence in the environment. Nevertheless, MPs toxicity studies in ruminants often lack attention. Here, we assessed the cytotoxicity of polystyrene microplastics (PS MPs) on goat mammary epithelial cells (GMECs). Compared to controls, PS MPs treatment significantly reduced cell viability, altered cell morphology and disrupted organelle integrity. Detection of membrane potential and reactive oxygen species (ROS) suggested that PS MPs induced mitochondrial dysfunction and oxidative stress. Further transcriptome analysis also confirmed alterations in these pathways. In addition, several genes related to endoplasmic reticulum (ER) homeostasis were significantly regulated in the transcriptional profile. Subsequent experiments confirmed that PS MPs induce ER stress via the PERK/eIF2α/CHOP pathway, accompanied by intracellular Ca2+ overload. Meanwhile, downstream activation of the Bax/Bcl-2 pathway and caspase cascade released apoptotic signals, which led to apoptosis in GMECs. Interestingly, the addition of PERK inhibitor (ISRIB) attenuated PS MPs-induced ER stress and apoptosis, which suggests that ER stress may exacerbate PS MPs-induced cytotoxicity. This work reveals the impact of MPs on mammalian cytotoxicity, enriches the mechanisms for the toxicity of MPs, and provides insight for further assessment of the risk of MPs in food.


Asunto(s)
Microplásticos , Plásticos , Animales , Humanos , Microplásticos/toxicidad , Microplásticos/metabolismo , Estrés del Retículo Endoplásmico , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Mamíferos/metabolismo
13.
Heliyon ; 10(7): e28630, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596092

RESUMEN

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.

14.
Ther Adv Neurol Disord ; 17: 17562864241239117, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616782

RESUMEN

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.


Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

15.
Food Res Int ; 167: 112682, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37087259

RESUMEN

Zinc oxide nanoparticles (ZnO NPs) have recently been used as food preservatives and additives because of their good antibacterial and nutritional functions. This study performed RNA-seq analyses to evaluate the potential toxicity of ZnO NPs on goat mammary epithelial cells (GMECs) in vitro. Our results suggested that the ZnO NP treatment significantly reduced GMEC viability in a time- and dose-dependent manner. Transcriptomic analysis showed that ZnO NP exposure changed the expression levels of more than 500 genes in GMECs, including various biological pathways. We observed that decreased mitochondrial membrane potential caused mitochondrial dysfunction. Further study indicated that the treatment of cells with ZnO NPs resulted in the accumulation of reactive oxygen species (ROS), which led to oxidative stress. Meanwhile, the expression of genes (TNFα, TNFR1, FADD, Caspase 8 and Caspase 6) associated with the death receptor pathway was upregulated, which indicated the death receptor-mediated extrinsic apoptosis pathway was activated. Moreover, the expression levels of Bax, Cytc, Caspase 3 and Caspase 9 were upregulated, while the expression levels of Bcl2 were downregulated, which indicated mitochondria-mediated intrinsic apoptosis pathway was activated. More notably, ZnO NP exposure increased the expression levels of ER stress-related genes (PERK, ATF4, eIF2α and CHOP) and proteins (p-PERK, p-eIF2α, PERK and CHOP). Furthermore, gene ontology (GO) terms and genes related to autophagy were altered, suggesting that exposure to ZnO NPs might activate autophagy in GMECs. In summary, our findings showed that ZnO NPs could exert significant toxic effects on GMECs through multiple mechanisms. These pathways are related to each other and influence each other to participate in ZnO NPs-induced the damage of GMECs. Thus, their safe use in the feed and food industry should be considered. Meanwhile, RNA-seq might represent a new method of assessing the toxicity mechanisms of nanomaterials.


Asunto(s)
Nanopartículas , Óxido de Zinc , Animales , Óxido de Zinc/toxicidad , Aditivos Alimentarios , Cabras , Nanopartículas/toxicidad , Células Epiteliales , Receptores de Muerte Celular
16.
Front Immunol ; 14: 1120894, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969186

RESUMEN

Background: Encephalitis has been recognized in patients with autoimmunity related to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) antibodies; however, patients with meningoencephalitis associated with those antibodies have been rarely identified in the medical literature. We aimed to define the frequency, clinical features, response to therapy, and functional outcomes of patients with meningoencephalitis associated with GAD antibodies. Methods: We retrospectively studied consecutive patients attending a tertiary care center for evaluation of an autoimmune neurological disorder from January 2018 to June 2022. The modified Rankin Scale (mRS) was used to assess the functional outcome at the last follow-up. Results: We evaluated 482 patients with confirmed autoimmune encephalitis during the study period. Four among the 25 patients with encephalitis related to GAD65 antibodies were identified. One patient was excluded owing to the coexistence of NMDAR antibodies. Three male patients aged 36, 24, and 16 years had an acute (n = 1) or subacute (n = 2) onset of confusion, psychosis, cognitive symptoms, seizures, or tremor. No patient had fever or clinical signs of meningeal irritation. Mild pleocytosis (<100 leukocytes/106) was identified in two patients, whereas one patient had normal CSF. Following immunotherapy with corticosteroids (n = 3) or intravenous immunoglobulin (n = 1), significant improvement was observed in all three cases, achieving a good outcome (mRS 1) in all cases. Conclusion: Meningoencephalitis is an uncommon presentation of GAD65 autoimmunity. Patients present with signs of encephalitis but with meningeal enhancement and have good outcomes.


Asunto(s)
Encefalitis , Meningoencefalitis , Humanos , Masculino , Autoanticuerpos , Autoinmunidad , Encefalitis/diagnóstico , Encefalitis/terapia , Glutamato Descarboxilasa , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Estudios Retrospectivos , Adolescente , Adulto Joven , Adulto
17.
Front Neurol ; 13: 929778, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35769364

RESUMEN

Objective: We present a rare case with anti-Homer-3 antibodies positive encephalitis in the youngest patient ever identified and reviewed the literature. Case Report: A 10-year-old, Chinese boy came for evaluation of a 2-week history of cognitive impairment, irritability, dysarthria, and cautious gait. The neurological examination was consistent with the pan-cerebellar syndrome and encephalopathy. Cerebrospinal fluid (CSF) was inflammatory with increased leukocytes. Magnetic resonance imaging of the brain showed hyperintensities in both cerebellar hemispheres and vermis in Fluid-attenuated inversion recovery (FLAIR) and T2- weighted sequences. Infectious disorders were ruled out, but positivity for anti-Homer-3 antibodies was detected in the CSF, but not in the serum. Additionally, low titers of voltage-gated calcium channel (VGCC) antibodies were found in the serum. Treatment with intravenous (IV) corticosteroids did not provide meaningful clinical improvement; however, the patient achieved almost complete recovery (modified Ranking Scale score: 1) following IV immunoglobulin. Conclusion: Anti-Homer-3 cerebellar ataxia with encephalopathy should be considered within the differential diagnosis of acute inflammatory cerebellar disease in children and it may coexist with VGCC antibodies.

18.
Mult Scler Relat Disord ; 68: 104151, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36088728

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.


Asunto(s)
Esclerosis Múltiple , Masculino , Femenino , Humanos , Adulto , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/diagnóstico , Estudios Prospectivos , Prevalencia , China/epidemiología , Ciudades
19.
Biology (Basel) ; 10(6)2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34070240

RESUMEN

Estrous cycle is one of the placental mammal characteristics after sexual maturity, including estrus stage (ES) and diestrus stage (DS). Estrous cycle is important in female physiology and its disorder may lead to diseases, such as polycystic ovary syndrome, ovarian carcinoma, anxiety, and epilepsy. In the latest years, effects of non-coding RNAs and messenger RNA (mRNA) on estrous cycle have started to arouse much concern, however, a whole transcriptome analysis among non-coding RNAs and mRNA has not been reported. Here, we report a whole transcriptome analysis of goat ovary in estrus and diestrus periods. Estrus synchronization was conducted to induce the estrus phase and on day 32, the goats shifted into the diestrus stage. The ovary RNA of estrus and diestrus stages was respectively collected to perform RNA-sequencing. Then, the circular RNA (circRNA), microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA databases of goat ovary were acquired, and the differential expressions between estrus and diestrus stages were screened to construct circRNA-miRNA-mRNA/lncRNA and lncRNA-miRNA/mRNA networks, thus providing potential pathways that are involved in the regulation of estrous cycle. Differentially expressed mRNAs, such as MMP9, TIMP1, 3BHSD, and PTGIS, and differentially expressed miRNAs that play key roles in the regulation of estrous cycle, such as miR-21-3p, miR-202-3p, and miR-223-3p, were extracted from the network. Our data provided the miRNA, circRNA, lncRNA, and mRNA databases of goat ovary and each differentially expressed profile between ES and DS. Networks among differentially expressed miRNAs, circRNAs, lncRNAs, and mRNAs were constructed to provide valuable resources for the study of estrous cycle and related diseases.

20.
Front Immunol ; 12: 705536, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367165

RESUMEN

Background: Neuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood. Purpose: To detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value. Methods: We obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA. Results: Serum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores. Conclusions: Our results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.


Asunto(s)
Heparitina Sulfato , Ácido Hialurónico , Neuromielitis Óptica , Gravedad del Paciente , Adulto , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Femenino , Heparitina Sulfato/sangre , Heparitina Sulfato/líquido cefalorraquídeo , Humanos , Ácido Hialurónico/sangre , Ácido Hialurónico/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/sangre , Neuromielitis Óptica/líquido cefalorraquídeo
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