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Conformational biosensors to monitor the activation state of G protein-coupled receptors are a useful addition to the molecular pharmacology assay toolbox to characterize ligand efficacy at the level of receptor proteins instead of downstream signaling. We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor (H3R) biosensor that allowed the detection of both (partial) agonism and inverse agonism on living cells in a microplate reader assay format upon stimulation with H3R ligands. In the current study, we have further characterized this H3R biosensor on intact cells by monitoring the effect of consecutive ligand injections in time and evaluating its compatibility with photopharmacological ligands that contain a light-sensitive azobenzene moiety for photo-switching. In addition, we have validated the H3R biosensor in membrane preparations and found that observed potency values better correlated with binding affinity values that were measured in radioligand competition binding assays on membranes. Hence, the H3R conformational biosensor in membranes might be a ready-to-use, high-throughput alternative for radioligand binding assays that in addition can also detect ligand efficacies with comparable values as the intact cell assay.
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Técnicas Biosensibles , Receptores Histamínicos H3 , Membrana Celular/metabolismo , Ligandos , Receptores Histamínicos , Receptores Histamínicos H3/metabolismoRESUMEN
The histamine H1 receptor (H1R) is a G protein-coupled receptor (GPCR) and plays a key role in allergic reactions upon activation by histamine which is locally released from mast cells and basophils. Consequently, H1R is a well-established therapeutic target for antihistamines that relieve allergy symptoms. H1R signals via heterotrimeric Gq proteins and is phosphorylated by GPCR kinase (GRK) subtypes 2, 5, and 6, consequently facilitating the subsequent recruitment of ß-arrestin1 and/or 2. Stimulation of a GPCR with structurally different agonists can result in preferential engagement of one or more of these intracellular signaling molecules. To evaluate this so-called biased agonism for H1R, bioluminescence resonance energy transfer (BRET)-based biosensors were applied to measure H1R signaling through heterotrimeric Gq proteins, second messengers (inositol 1,4,5-triphosphate and Ca2+), and receptor-protein interactions (GRKs and ß-arrestins) in response to histamine, 2-phenylhistamines, and histaprodifens in a similar cellular background. Although differences in efficacy were observed for these agonists between some functional readouts as compared to reference agonist histamine, subsequent data analysis using an operational model of agonism revealed only signaling bias of the agonist Br-phHA-HA in recruiting ß-arrestin2 to H1R over Gq biosensor activation.
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Técnicas Biosensibles , Histamina , Transferencia de Energía , Quinasas de Receptores Acoplados a Proteína-G/metabolismo , Proteínas de Unión al GTP/metabolismo , Células HEK293 , Histamina/farmacología , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Histamínicos H1/metabolismo , beta-Arrestinas/metabolismoRESUMEN
The modulation of biological processes with light-sensitive chemical probes promises precise temporal and spatial control. Yet, the design and synthesis of suitable probes is a challenge for medicinal chemists. This article introduces a photocaging strategy designed to modulate the pharmacology of histamine H3 receptors (H3R) and H4 receptors (H4R). Employing the photoremovable group BODIPY as the caging entity for two agonist scaffolds-immepip and 4-methylhistamine-for H3R and H4R, respectively, we synthesized two BODIPY-caged compounds, 5 (VUF25657) and 6 (VUF25678), demonstrating 10-100-fold reduction in affinity for their respective receptors. Notably, the caged H3R agonist, VUF25657, exhibits approximately a 100-fold reduction in functional activity. The photo-uncaging of VUF25657 at 560 nm resulted in the release of immepip, thereby restoring binding affinity and potency in functional assays. This approach presents a promising method to achieve optical control of H3R receptor pharmacology.
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Alternative splicing significantly enhances the diversity of the G protein-coupled receptor (GPCR) family, including the histamine H3 receptor (H3R). This post-transcriptional modification generates multiple H3R isoforms with potentially distinct pharmacological and physiological profiles. H3R is primarily involved in the presynaptic inhibition of neurotransmitter release in the central nervous system. Despite the approval of pitolisant for narcolepsy (Wakix®) and daytime sleepiness in adults with obstructive sleep apnea (Ozawade®) and ongoing clinical trials for other H3R antagonists/inverse agonists, the functional significance of the numerous H3R isoforms remains largely enigmatic. Recent publicly available RNA sequencing data have confirmed the expression of multiple H3R isoforms in the brain, with some isoforms exhibiting unique tissue-specific distribution patterns hinting at isoform-specific functions and interactions within neural circuits. In this review, we discuss the complexity of H3R isoforms with a focus on their potential roles in central nervous system (CNS) function. Comparative analysis across species highlights evolutionary conservation and divergence in H3R splicing, suggesting species-specific regulatory mechanisms. Understanding the functionality of H3R isoforms is crucial for the development of targeted therapeutics. This knowledge will inform the design of more precise pharmacological interventions, potentially enhancing therapeutic efficacy and reducing adverse effects in the treatment of neurological and psychiatric disorders.
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Empalme Alternativo , Isoformas de Proteínas , Receptores Histamínicos H3 , Humanos , Empalme Alternativo/genética , Receptores Histamínicos H3/metabolismo , Receptores Histamínicos H3/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , AnimalesRESUMEN
The histamine H3 receptor (H3R) regulates as a presynaptic G protein-coupled receptor the release of histamine and other neurotransmitters in the brain, and is consequently a potential therapeutic target for neuronal disorders. The human H3R encodes for seven splice variants that vary in the length of intracellular loop 3 and/or the C-terminal tail but are all able to induce heterotrimeric Gi protein signaling. The last two decades H3R drug discovery and lead optimization has been exclusively focused on the 445 amino acids-long reference isoform H3R-445. In this study, we pharmacologically characterized for the first time all seven H3R isoforms by determining their binding affinities for reference histamine H3 receptor agonists and inverse agonists. The H3R-453, H3R-415, and H3R-413 isoforms display similar binding affinities for all ligands as the H3R-445. However, increased agonist binding affinities were observed for the three shorter isoforms H3R-329, H3R-365, and H3R-373, whereas inverse agonists such as the approved anti-narcolepsy drug pitolisant (Wakix®) displayed significantly decreased binding affinities for the latter two isoforms. This opposite change in binding affinity of agonist versus inverse agonists on H3R-365 and H3R-373 is associated with their higher constitutive activity in a cAMP biosensor assay as compared to the other five isoforms. The observed differences in pharmacology between longer and shorter H3R isoforms should be considered in future drug discovery programs.
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Histamina , Receptores Histamínicos H3 , Humanos , Histamina/farmacología , Receptores Histamínicos H3/metabolismo , Agonismo Inverso de Drogas , Receptores Histamínicos , Isoformas de Proteínas , Agonistas de los Receptores Histamínicos/farmacologíaRESUMEN
The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor cells. The pro-death effect of Nur77 can be regulated by its interaction with Bcl-2, resulting in conversion of Bcl-2 from a survival to killer. As Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy, targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer therapeutics. Here, we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 pathway. In vitro and animal studies revealed an apoptotic effect of XS561 in a range of tumor cell lines including MDA-MB-231 triple-negative breast cancer (TNBC) and MCF-7/LCC2 tamoxifen-resistant breast cancer (TAMR) in a Nur77-dependent manner. Mechanistic studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria, resulting in mitochondria-related apoptosis. Interestingly, XS561-induced accumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 condensates. Together, our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in mediating the apoptotic effect of Nur77 at mitochondria.
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Background and objectives: Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the 'glymphatic system'. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients. Methods: We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity. Results: The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5). Discussion: In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.
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Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Biomarcadores , Humanos , Inmunoglobulina A , Inmunoglobulina G , Enfermedades Neuroinflamatorias , Albúmina SéricaRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD. METHODS: This was a single-center, single-arm, open-label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240 mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427). RESULTS: Eight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48 weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p < 0.001, power of test = 1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred. CONCLUSIONS: In this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy.
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Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Potenciales Evocados Visuales , Humanos , Inmunosupresores/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Intercambio Plasmático , Recurrencia , Retina/patologíaRESUMEN
Background: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD. Methods: The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion: Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients. Trial registration: The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.
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Nur77, an orphan nuclear receptor, is a member of the nuclear receptor superfamily. Nur77 plays important roles in various biological processes. Previously we reported that BI1071(DIM-C-pPhCF3+MeSO3-), an oxidized form and methanesulfonate salt of (4-CF3-Ph-C-DIM), can modulate Nur77's non-genomic apoptotic pathway through that Nur77 translocated from the nucleus to mitochondria to induce cytochrome c releasing and promote apoptosis of cancer cell. Here we report our efforts to further optimize BI1071. A series of BI1071 analogs were designed, synthesized and their apoptosis potency was systematically evaluated. Our preliminary structure-activity relationship study identified compound 10b as a better modulator with strong binding to Nur77 and enhanced apoptotic activity. Binding studies demonstrated that 10b could bind to its target Nur77 with an affinity value of 33 nM. Furthermore, mechanism studies reveal that 10b acts as an anticancer agent by utilizing the Nur77-Bcl-2 apoptotic pathway.
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Antineoplásicos/farmacología , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Simulación del Acoplamiento Molecular , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease that recurrently relapses and leads to severe disability. The available choices for disease prevention are few or intolerable. Previous studies suggested that telitacicept may provide a promising therapeutic strategy for autoimmune diseases involving B cells. Therefore, this study aims to assess the effectiveness and safety of telitacicept for recurrent NMOSD. Methods: We will perform a single-arm, single-center, open-label, specialist study with a total enrollment of eight participants. The treatment regimen includes plasma exchange three times and subcutaneous injection of telitacicept for 46 cycles, with a total period of 48 weeks. The primary endpoint is the time to first recurrence after enrollment. Secondary endpoints are Expanded Disability Status Scale (EDSS) score, Opticospinal Impairment Scale (OSIS) score, Hauser Ambulation Index, number of lesions on MRI, and changes in visual evoked potential (VEP), optical coherence tomography (OCT) and immunologic status. All adverse events after medication will be documented and investigated. Discussion: This study will explore the safety and effectiveness of telitacicept following plasma exchange regarding the time to recurrence in neuromyelitis optica spectrum disorder (NMOSD) for the first time. Clinical Trial Registration: Chictr.org.cn, identifier ChiCTR1800019427.
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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system. Serum albumin (SA) has antioxidant, immunomodulatory and anti-inflammatory effects. However, the roles of SA in NMOSD have not been studied. The current study aimed to clarify the association of SA with disease severity and prognosis in NMOSD patients. METHODS: Serum levels of albumin were measured by Bromcresol Green method. Serum level measurements of interleukins were performed using enzyme-linked immunoassay (ELISA) method. RESULTS: Of all the 130 NMOSD patients, 96 patients were in the acute phase while 34 patients were in the remission phase of disease at the time of sampling. SA concentration was significantly correlated with EDSS score in patients in the acute phase but not in remission phase (r = - 0.388, p < 0.001 and r = - 0.467, p = 0.809, respectively). Logistic analysis revealed that SA was the only significant factor to predict severe NMOSD (EDSS 8.0-9.5) OR = 0.698, 95%CI 0.563-0.865, p = 0.001) after adjustment of other confounding factors. Furthermore, SA was negatively correlated with the serum level of IL-33 (r = -0.438, p = 0.016) in the acute phase of NMOSD patients. CONCLUSION: The current study found that low level of SA was an independent indicator of more severe neurological deficit in patients in acute phase of NMOSD. SA concentration was negatively correlated with the serum level of IL-33 in the acute phase of the disease, which implies that SA might participate in the immunopathology of NMOSD partly through its interaction with IL-33.
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Neuromielitis Óptica , Albúmina Sérica , Humanos , Interleucinas , Neuromielitis Óptica/sangre , Neuromielitis Óptica/fisiopatología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The impact of vitamin D have been studied in neuroinflammation disorders, and as the newly discovered Th2-related cytokines, IL-25, IL-31 and IL-33 may also play important roles in the lesions of neuromyelitis optica spectrum disorders (NMOSD). This study sought to investigate the clinical profiles of vitamin D and Th2 axis-related cytokines and their relationships in patients with NMOSD. METHODS: Eighty-four NMOSD patients and 84 healthy controls (HC) were evaluated for serum levels of the total vitamin D [25(OH)D], 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] by means of high performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). Meanwhile, serum AQP4-IgG (nâ¯=â¯84) were detected by an AQP4-transfected cell-based assay (CBA) and IL-25, IL-31, IL-33 (nâ¯=â¯32) were performed using enzyme-linked immunoassay (ELISA) method. RESULTS: The serum levels of 25(OH)D, 25(OH)D2 and 25(OH)D3 were significantly lower in NMOSD group as compared to HC group. There were also significant differences in serum vitamin D levels between the acute phase group and remission group except the 25(OH)D2 levels (pâ¯=â¯0.070). No correlations were detected between vitamin D and disease activity or vitamin D and disease disability. Furthermore, serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were not correlated with serum IL-25, IL-31, and IL-33 levels, the location of lesions and the number of lesion locations. CONCLUSION: Our result showed hypovitaminosis D in NMOSD patients. The activity of 25(OH)D3 seemed to be closer to 25(OH)D than 25(OH)D2. Low levels of 25(OH)D/25(OH)D3 might represent a risk factor for the disease activity in patients with NMOSD.
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Citocinas/sangre , Neuromielitis Óptica/sangre , Vitamina D/sangre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/inmunología , Espectrometría de Masas en Tándem , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Nur77 (also called TR3 or NGFI-B), an orphan member of the nuclear receptor superfamily, induces apoptosis by translocating to mitochondria where it interacts with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic molecule. Nur77 posttranslational modification such as phosphorylation has been shown to induce Nur77 translocation from the nucleus to mitochondria. However, small molecules that can bind directly to Nur77 to trigger its mitochondrial localization and Bcl-2 interaction remain to be explored. Here, we report our identification and characterization of DIM-C-pPhCF3 +MeSO3 - (BI1071), an oxidized product derived from indole-3-carbinol metabolite, as a modulator of the Nur77-Bcl-2 apoptotic pathway. BI1071 binds Nur77 with high affinity, promotes Nur77 mitochondrial targeting and interaction with Bcl-2, and effectively induces apoptosis of cancer cells in a Nur77- and Bcl-2-dependent manner. Studies with animal model showed that BI1071 potently inhibited the growth of tumor cells in animals through its induction of apoptosis. Our results identify BI1071 as a novel Nur77-binding modulator of the Nur77-Bcl-2 apoptotic pathway, which may serve as a promising lead for treating cancers with overexpression of Bcl-2.
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Hidrocarburos Fluorados/farmacología , Indoles/farmacología , Neoplasias/tratamiento farmacológico , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Animales , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HCT116 , Humanos , Indoles/química , Células MCF-7 , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Neoplasias/genética , Neoplasias/patología , Unión Proteica , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIMS: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system. Increasing evidence indicates that NMOSD is a Th2- and Th17-dominant disease. IL-25, IL-31, and IL-33 are three newly found Th2-related cytokines, and their roles in the pathogenesis of NMOSD have not been studied. This study aimed to measure the serum levels of IL-25, IL-31, and IL-33 in patients with NMOSD and evaluate their clinical implications. METHODS: Serum was collected from patients with NMOSD (n = 48) and healthy controls (HC, n = 28). Serum level measurements of IL-25, IL-31, IL-33, IL-17A, and IL-6 were performed using enzyme-linked immunoassay (ELISA) method. RESULTS: The serum levels of IL-25, IL-31, and IL-33 were significantly higher in patients with NMOSD as compared to HC. The serum level of IL-31 was significantly correlated with IL-17A (r = 0.382,P = 0.009) in patients with NMOSD; the latter is a critical cytokine in the pathogenesis of NMOSD. The serum level of IL-33 was higher in patients with characteristic brain lesions than patients without (307 pg/mL vs 166 pg/mL, P = 0.028). Furthermore, the serum level of IL-33 in the acute phase of the disease was positively correlated with annualized relapse rate (r = 0.364, P = 0.04). CONCLUSION: We found higher serum levels of IL-25, IL-31, and IL-33 in patient with NMOSD as compared to healthy controls. The serum level of IL-33 during acute phase was associated with more past attacks in patients with NMOSD.
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Citocinas/sangre , Neuromielitis Óptica/sangre , Adulto , Anticuerpos/sangre , Acuaporina 4/inmunología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/inmunología , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: It was still rare for the quantitative magnetic resonance imaging (MRI) research of regional changes in hippocampus sclerosis (HS) in Chinese patients with epilepsy. This study aimed to study the hippocampal volumes (HVs) with quantitative MRI measurement in Chinese patients with epilepsy. METHODS: Forty-six Chinese patients with epilepsy (intractable epilepsy (IE), n = 21; non-intractable epilepsy (NIE), n = 25) and 25 normal controls were collected between July 2007 and March 2008. All of the subjects underwent a 3T high-resolution MRI with oblique coronal thin sections oriented perpendicular to the hippocampal long axis. Hippocampal structures were assessed by visual detection, and HVs were quantitatively studied with a Picture Archiving and Communication System (PACS). RESULTS: Our study suggested that there was no significant difference in gender (P > 0.05) while the right hippocampal head volume (HHV), hippocampal body volume (HBV), and the whole hippocampal volume (HCV) were greater than the left one (P < 0.05), but no significant difference was found in bilateral hippocampal tail volume (HTV) (P > 0.05) in normal controls. That unilateral/diffuse (64%/21%) and bilateral/focal (86%/20%) hippocampal atrophy (HA) were significant in IE and NIE patients, respectively. Anterior hippocampus, especially HHV (26% in IE and 20% in NIE) and HBV (29% in IE and 12% in NIE), had more significant atrophy than the HTV (5% in IE and 0% in NIE) in patients with epilepsy. CONCLUSION: By assessing the volumes of the regional hippocampus with 3T MRI, we could better define the range and distribution of HS, since regional or subtle changes in HVs could be detected earlier with 3T MRI.