RESUMEN
BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.
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Calcinosis , Mutación , Linaje , Humanos , Masculino , Calcinosis/genética , Calcinosis/patología , Femenino , Dineínas Axonemales/genética , Adulto , Trastornos de la Motilidad Ciliar/genética , Encefalopatías/genética , Fenotipo , Células HEK293 , China , Empalme del ARN/genética , Persona de Mediana Edad , Glicósido HidrolasasRESUMEN
OBJECTIVE: Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. DATA SOURCES: Articles referred in this review were collected from the database of PubMed published in English up to January 2018. STUDY SELECTION: We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed. RESULTS: It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. CONCLUSIONS: In view of the redundancy of cytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.
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Asma/metabolismo , Citocinas/fisiología , Interleucina-17/fisiología , Interleucina-33/fisiología , Asma/fisiopatología , Humanos , Linfopoyetina del Estroma TímicoRESUMEN
By a reflux process, we prepared Ni-NiO nanocomposites that are face-centered cubic (fcc). By tuning the precursor concentration, we controlled the Ni content in the Ni-NiO nanocomposites. We found that both the interface of Ni and NiO crystal lattices and the weight fraction of Ni have significant impacts on their magnetic properties. There is increase of saturation magnetization and decrease of coercivity (HC) with the increase of the Ni weight fraction. Large exchange bias (HE) and enhanced HC are observed at 5 K, which are due to the creation of heterojunctions at the interfaces of ferromagnetic Ni and antiferromagnetic NiO. After optimization, it is observed that the Ni-NiO nanocomposites with an Ni content of 2.6% show an HC and HE of 1068 and 350 Oe, respectively.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Puerarin is the most abundant isoflavonoid in Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for treating fever in China for a long history. AIM OF THE STUDY: The present study aimed at evaluating the antipyretic effect of puerarin and revealing the related mechanisms. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced fever in rats was used to assess the antipyretic effect of puerarin. After an intraperitoneal injection of LPS (100µg/kg), body temperature was tested every 30min up to 8h. Different doses of puerarin (25, 50, 100mg/kg) were intraperitoneally administered 30min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells were treated with various concentrations of puerarin (25-200µM). The pyrogenic mediators, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide (NO), were examined on both transcription and expression levels. Furthermore, the influences of the activation of nuclear factor-kappa B (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were assayed by western blot. RESULTS: The intraperitoneal administration of puerarin at test doses clearly demonstrated apparent antipyretic effect through the declines in body temperature elevated by LPS in rats. The in vitro data showed that puerarin inhibited the production of IL-1ß, TNF-α, IL-6, PGE(2) and NO; moreover, the RT-PCR analysis and the western blot analysis indicated that puerarin regulated the transcriptional level via suppression of NF-κB activation and blockade of MAPK signal pathway. CONCLUSIONS: In summary, the antipyretic property of puerarin might result, at least in part, from an inhibition of endogenous pyrogen production and expression. Taken in this sense, our findings provide an explanation for puerarin acting as an important constituent in Gegen, thus, provide scientific basis for the wide use of Radix Puerariae in China as a traditional antipyretic.
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Antipiréticos/farmacología , Regulación de la Temperatura Corporal/efectos de los fármacos , Fiebre/tratamiento farmacológico , Isoflavonas/farmacología , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Animales , Antipiréticos/administración & dosificación , Western Blotting , Línea Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Fiebre/inducido químicamente , Fiebre/genética , Fiebre/inmunología , Fiebre/fisiopatología , Regulación de la Expresión Génica , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Isoflavonas/administración & dosificación , Macrófagos/inmunología , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosforilación , Fitoterapia , Plantas Medicinales , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transcripción GenéticaAsunto(s)
Adenocarcinoma de Células Claras/patología , Cavidad Nasal , Neoplasias Nasales/patología , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/cirugía , Adulto , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Diagnóstico Diferencial , Humanos , Queratinas/metabolismo , Masculino , Neoplasias Nasales/metabolismo , Neoplasias Nasales/cirugía , Proteínas S100/metabolismoRESUMEN
A phytochemical investigation of the anomalous fruits of Gleditisia sinensis led to one new oleanane-type triterpenoid saponin acylated with one monoterpenic acid, 3-O-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-alpha-L-rhamnopyranosyl-(1 --> 2)-[(6S,2E)-6-hydroxy-2,6-dimethyl-2,7-octadienoyl-(1 --> 6)]-beta-D-glucopyranosyl ester, named gleditsioside Z (1), together with nine known ones (2-10). Their structural details were mainly established on the basis of 1D, 2D NMR and HR-MS analysis as well as some chemical methods. Structure-activity relationships of the isolated saponins that affected nitric oxide production from cultured mouse macrophages (RAW 264.7 cell lines) induced by lipopolysaccharide were discussed.
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Gleditsia/química , Lipopolisacáridos/farmacología , Óxido Nítrico/biosíntesis , Saponinas/química , Triterpenos/química , Animales , Línea Celular , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Saponinas/farmacología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: To investigate the anti-oxidative effect of Angelica polysaccharide sulphate( APS). METHODS: The Hela cells were cultured conventionally. Then APS was added and cultured together in different concentration for 24h followed by a oxidative injury with H2O2 or UV irradiation. The anti-oxidative effects of APS were detected as follow: cell viability was measured by MTT assay; colorimetric analysis was used to determine SOD activity, GSH and MDA level in cytoplasm. RESULTS: Treatment of H2O2 or UV irradiation significantly decreased cell viability, GSH and SOD activity in cytoplasm,while increased MDA in cytoplasm. At the range of 0. 3 -100microg/ml, APS significantly increased cell viabilty, GSH and SOD activity,while decreased MDA in a dose dependent manner( P < 0. 05 or P <0.01). CONCLUSION: APS has anti-oxidative effect,which may be one of its anti-AIDS mechanisms.