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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 52-56, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922597

RESUMEN

OBJECTIVE: To delineate the clinical features,inheritance pattern, and genotype-phenotype correlation of a Chinese patient with a 17q25.3 duplication. METHODS: Whole exome sequencing(WES), chromosomal microarray analysis (CMA), chromosomal karyotyping and fluorescence in situ hybridization (FISH) were employed for the analysis of the proband and his family members. RESULTS: A 5.7 Mb duplication at 17q25.3→qter was identified by WES and CMA in the 4-year-old boy with multiple congenital anomalies, which was classified as a clinically pathogenic variant. This duplication was confirmed by FISH, and was inherited from his unaffected mother who carried a balanced translocation. Further study revealed that his grandmother also carried the balanced translocation but had gestated three healthy children and had no abortion history. His uncle also carried the balanced translocation, while his aunt was normal. CONCLUSION: Above results have enriched the clinical phenotypes of 17q25.3 duplication. Genetic counseling was provided for the family. P4HB, ACTG1, BAIAP2 and TBCD genes may underlie the clinical features for the 17q25.3 duplication.


Asunto(s)
Anomalías Múltiples , Duplicación Cromosómica , Cromosomas Humanos Par 17 , Discapacidades del Desarrollo , Anomalías Múltiples/genética , Adulto , Preescolar , China , Cromosomas Humanos Par 17/genética , Discapacidades del Desarrollo/genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Proteínas Asociadas a Microtúbulos , Translocación Genética
2.
Eur J Med Genet ; 63(1): 103611, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30615951

RESUMEN

Xia-Gibbs syndrome is a rare genetic condition characterized by intellectual disability, growth retardation, delayed psychomotor development with absent or poor expressive language, distinctive facial features, hypotonia, laryngomalacia and obstructive sleep apnea. At present, Xia-Gibbs syndrome has been reported to be mainly caused by truncating mutations in AHDC1 gene located on chromosome 1p36.11. However, the evidence supporting AHDC1 deletion as a cause of this syndrome is still limited. Here we report an 8-year-old boy carrying a de novo 575 Kb microdeletion at 1p36.11 including AHDC1 gene. The boy is characterized by intellectual disability, developmental delay, short stature, expressive language delay, facial dysmorphism, obstructive sleep apnea and multiple congenital anomalies, which are mostly consistent with the characteristics of Xia-Gibbs syndrome. Therefore, we provide further supporting evidence that AHDC1 deletion causes Xia-Gibbs syndrome through a haploinsufficiency mechanism. Currently, clinical consequences of AHDC1 gene duplication has never been reported. Here, we identify a de novo 480 Kb duplication at 1p36.11p35.3 spanning the entire AHDC1 gene in a 2-year-8-month boy, who displays similar clinical features with that of Xia-Gibbs syndrome, in particular, expressive language delay, hypotonia, laryngomalacia and obstructive sleep apnea, as well as mirrored phenotypes such as overgrowth and advanced bone age. WES test excludes to the degree possible other known genetic causes. This case suggests that AHDC1 gene duplication may be clinical significance.

3.
Gynecol Obstet Invest ; 85(1): 53-71, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31505492

RESUMEN

OBJECT: The purpose of this review is to assess the diagnostic performance of different imaging techniques for the detection of para-aortic lymph node (PALN) metastasis from gynecological malignancies. METHODS: Six databases, from the earliest available date of indexing through July 22, 2018, were systematically searched. In addition, the reference lists of relevant articles were searched by hand. Study allocation, data extraction, and quality assessment were independently performed by 2 reviewers. The size effect, sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, diagnostic OR, and 95% CIs were used in the meta-analysis. The area under the curve (AUC) and Q* were calculated to reflect the synthesized diagnostic accuracy. Statistical calculations of this meta-analysis were conducted using STATA version 14.0 software. RESULTS: Across 41 eligible studies (1,615 participants), pooled SEN, SPE, and AUC of magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, and lymphangiography analyses were 25%, 93%, 0.7675; 60%, 94%, 0.9050; 83%, 96%, 0.9422; 66%, 97%, 0.9501; 77%, 75%, 0.8332, respectively. Analysis of combined summary receiver operating characteristic curves indicated that PET and PET-CT were superior to other imaging modalities. CONCLUSION: The present meta-analysis demonstrated that PET and PET-CT should be the first choice for detecting PALN metastasis in gynecological malignancies. CT was also suitable for confirmation. MRI was not recommended. Further studies are needed for PALN assessment.

5.
Artículo en Inglés | MEDLINE | ID: mdl-31767415

RESUMEN

Hypochlorous/hypochlorite (HClO/ClO-), one of the most important signal molecule, plays a crucial role in many cellular signaling pathways. It is reported that the HClO/ClO- level in mitochondria is important to maintain the normal mitochondrial function. Herein, we present two simple fluorescent probes BAC and mitochondria-targeting fluorescent probe TACB for the detection of ClO-. Probes BAC &TACB could be sensitively and selectivity detecting ClO- at the nanomolar levels with the detection limit of 1.64 × 10-9 M and 9.86 × 10-8 M, respectively. Additionally, probes BAC &TACB with the response unit of CO moiety could selectively detect ClO- over other various analytes such as anions, metal ions and OH, 1O2, H2O2. The response time of probe TACB for ClO- (<20 s), implying that it could offer a real-time analytical assay of ClO-. Finally, probe BAC was used for monitoring the ClO- in HEK293T cells and probe TACB could be utilized to track the fluctuations of exogenous ClO- levels in the mitochondria of Hela cells.

6.
Int J Surg ; 69: 153-164, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31400504

RESUMEN

BACKGROUND: Despite a burgeoning literature during the last two decades regarding perioperative risk management of anal fistula, little is known about its risk factors that influence postoperative recurrence. We performed a meta-analysis to summarize and assess the credibility of evidence of potential risk factors for anal fistula recurrence (AFR) after surgery. METHODS: Pubmed and EMBASE without language restriction were searched from inception to April 2018 that reported risk factors which predisposed recurrence after anal fistula surgery. We excluded studies that involved patients with anal fistula associated with Crohn's disease. MOOSE guidelines were followed when this meta-analysis was performed. We used random-effects models to pool relative risks (RRs) with 95% confidence intervals (CIs). Evidence from observational studies was graded into high-quality (Class I), moderate-quality (Class II/III) and low-quality (Class IV) based on Egger's P value, total sample size and between-study heterogeneity. RESULTS: Of 3514 citations screened, 20 unique observational studies comprising 6168 patients were involved in data synthesis. High-quality evidence showed that AFR was associated with high transsphincteric fistula (RR, 4.77; 95% CI, 3.83 to 5.95), internal opening unidentified (RR, 8.54; 95% CI, 5.29 to 13.80), and horseshoe extensions (RR, 1.92; 95% CI, 1.43 to 2.59). Moderate-quality evidence suggested an association with prior anal surgery (RR, 1.52; 95% CI, 1.04 to 2.23), seton placement surgery (RR, 2.97; 95% CI, 1.10 to 8.06), and multiple fistula tract (RR, 4.77; 95% CI, 1.46 to 15.51). High-quality evidence demonstrated no significant association with gender or smoking; moderate-quality evidence also suggested no association with age, tertiary referral, alcohol use, diabetes mellitus, obesity, preoperative seton drainage, high internal opening, postoperative drainage, mucosal advancement flap surgery, supralevator extensions, location or type of anal fistula. CONCLUSION: Several patient, surgery and fistula-related factors are significantly associated with postoperative AFR. These findings strengthen clinical awareness of early warning to identify patients with high-risk disease recurrence for AFR.


Asunto(s)
Fístula Rectal/cirugía , Adulto , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/etiología , Fístula Rectal/etiología , Recurrencia , Factores de Riesgo
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 221: 117187, 2019 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-31158759

RESUMEN

A coumarin-based turn on probe, named 3-((E)-3-(1H-indol-3-yl)acryloyl)-2H-chromen-2-one(IAC) was designed and synthesized for the detection of H2S in aqueous medium. IAC showed no obvious red fluorescence in Tris-HCl(pH = 7.2, 60% DMF), a 28.2-fold fluorescence enhancement was found when 40 equiv. H2S was added. Other analytes such as anions, metal ions and GSH, Cys, Gly did no significant fluorescence enhancement at 580 nm to IAC. The red fluorescence enhancement mechanism between IAC and H2S was considered by DFT and ESI-MS. Overall, IAC was successfully applied in cell imaging.


Asunto(s)
Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/química , Imagen Molecular/métodos , Cumarinas/química , Teoría Funcional de la Densidad , Colorantes Fluorescentes/farmacocinética , Colorantes Fluorescentes/toxicidad , Agua Dulce/análisis , Agua Dulce/química , Células HEK293 , Humanos , Sulfuro de Hidrógeno/farmacología , Límite de Detección , Microscopía Confocal/instrumentación , Espectrometría de Fluorescencia , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Ultravioleta , Factores de Tiempo
8.
Talanta ; 202: 190-197, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31171169

RESUMEN

It is necessary to develop simple and highly sensitive methods for the detection of hypochlorous acid (HOCl)/hypochlorite (ClO-) to ravel its relationship with disease. In this paper, a novel bio-compatible fluorescent (Z)-8-(hydrazonomethyl)-7-hydroxy-4-methyl-2H-chromen-2-one (probe 1b) based on coumarin was synthesized and used for detecting ClO- in PBS buffer (pH = 7.2, 10 mM, 60% C2H5OH). Probe 1b showed a remarkable fluorescence change from yellow to blue with the limit of detection as low as 2.4 × 10-9 M-1 when ClO- was added. The coexisted anions, metal ions and reactive oxygen species (•OH, 1O2, H2O2, KO2) showed any competitiveness towards ClO-. In response to ClO-, the fluorescence emission intensity of probe 1b was obviously enhanced within 20 s. The mechanism was confirmed by the ESI - MS and density functional theory calculations (DFT) to reveal that the coumarin lactone bonds C - O was cleavaged by oxidation of ClO-. What's more, probe 1b could be used in practical water samples and showed well recovery. Additionally, the cell imaging experiment was demonstrated that probe 1b could be effectively exploited to imaging exogenous ClO- in vitro.


Asunto(s)
Cumarinas/química , Colorantes Fluorescentes/química , Ácido Hipocloroso/análisis , Imagen Óptica , Células Cultivadas , Cumarinas/síntesis química , Colorantes Fluorescentes/síntesis química , Células HEK293 , Humanos , Estructura Molecular , Teoría Cuántica
9.
Future Oncol ; 15(15): 1729-1744, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31038361

RESUMEN

Aims: To investigate roles of miR-29a-DNMT1-SOCS1 axis in cervical cancer invasion and migration. Materials & methods: The methylation level of SOCS1 was determined by methylation specific PCR. The cell apoptosis, proliferation, migration and invasion were examined by Annexin-V/PI staining, MTT and colony formation assays, plus scratch and transwell assays respectively. The expressions of epithelial-mesenchymal transition and NF-κB related proteins were determined by western blotting. Results: MiR-29a was downregulated, accompanied with DNMT1 upregulation and SOCS1 downregulation in cervical cancer tissues. MiR-29a suppressed DNMT1, inhibited SOCS1 promoter methylation and upregulated its expression. Moreover, miR-29a promoted cell apoptosis, suppressed proliferation, inhibited migration and invasion via inactivation of NF-κB signaling pathway in cervical cancer cells. Conclusion: MiR-29a-DNMT1-SOCS1 axis plays an important role on invasion and metastasis in cervical cancer via NF-κB signaling pathway.


Asunto(s)
Metilación de ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , Proteína 1 Supresora de la Señalización de Citocinas/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , ADN (Citosina-5-)-Metiltransferasa 1/genética , Decitabina/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Humanos , Persona de Mediana Edad , FN-kappa B/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias
10.
Gene ; 705: 167-176, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31026569

RESUMEN

Hemorrhoid is a common and recurrent proctological disease, which is often accompanied by angiogenesis and edema. MicroRNAs in the DLK1-DIO3 imprinted clusters are involved in the development and pathogenesis of mammalian hemorrhoids. Results of the present study indicated multiple, differential expression of DLK1-DIO3 imprinted cluster microRNA between hemorrhoid and normal tissues, where miR-412-5p expression in hemorrhoid tissue was significantly decreased. Fluorescein reporter assays showed that miR-412-5p silenced Xpo1 mRNA expression by targeting its 3'-UTR. Overexpression of miR-412-5p in human umbilical vein endothelial cells (HUVECs) indicated that proliferation, migration and formation of vascular structures in HUVECs were inhibited in vitro. In addition, overexpression of miR-412-5p significantly inhibited Xpo1 expression and promoted upregulation of the p53 protein and its retention in the nucleus. Simultaneously, expression of p66SHC and p16 proteins was activated. In summary, downregulation of endogenous miR-412-5p expression in hemorrhoid vascular endothelial cells leads to high expression of the target gene Xpo1 and translocation of the p53 protein out of the nucleus, rendering it unable to activate p66SHC and p16. This ultimately weakens regulation of the vascular endothelial cell cycle, thereby accelerating the division of hemorrhoid vascular endothelial cells, leading to angiogenesis.


Asunto(s)
Hemorroides/genética , Carioferinas/genética , MicroARNs/genética , Neovascularización Patológica/genética , Receptores Citoplasmáticos y Nucleares/genética , Regiones no Traducidas 3' , Adulto , Movimiento Celular , Núcleo Celular/metabolismo , Proliferación Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica , Impresión Genómica , Hemorroides/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Transducción de Señal , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
11.
Life Sci ; 231: 116335, 2019 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-30898647

RESUMEN

BACKGROUND: PD-L1 enhanced the tumorigenesis and immune escape abilities of cancers. The upstream mechanisms of PD-L1 in regulating tumorigenesis and immune escape of diffuse large B cell lymphoma (DLBCL) remained unclear. METHODS: Human DLBCL cell line OCI-Ly10 and DLBCL patient samples were used in this study. MALAT1 was knocked down by shRNA. MiR-195 was inhibited by miR-195 inhibitor. Levels of MALAT1, PD-L1, miR-195 and CD8 were detected by RT-qPCR. Protein levels of PD-L1, Ras, p-ERK1/2, ERK1/2, Slug, E-cadherin, N-cadherin, Vimentin were detected by western blotting. The interaction between MALAT1 and miR-195, miR-195 and PD-L1 were detected by luciferase assay. OCI-Ly10 cell proliferation and apoptosis were detected by MTT and Annexin V/PI assays, respectively. Migration was detected by transwell assay. Cytotoxicity of CD8+ T cells was detected by LDH cytotoxicity kit. Proliferation and apoptosis of CD8+ T cell co-cultured with OCI-Ly10 cells were analyzed by CFSE and Annexin V/PI staining. RESULTS: MALAT1, PD-L1 and CD8 were up-regulated in DLBCL tissues while miR-195 was down-regulated. MiR-195 was negatively correlated with MALAT1 and PD-L1. MALAT1 could sponge miR-195 to regulate the expression of PD-L1. shMALAT1 treatment increased miR-195 level and decreased PD-L1 level. It also inhibited cell proliferation, migration and immune escape ability while increased apoptosis ratio of OCI-Ly10 cells. shMALAT1 treatment in OCI-Ly10 cells also promoted proliferation and inhibited apoptosis of CD8+ T cells. Knocking down of MALAT1 also suppressed EMT-like process via Ras/ERK signaling pathway. These effects were all rescued by miR-195 inhibitor. CONCLUSION: Long non-coding RNA MALAT1 sponged miR-195 to regulate proliferation, apoptosis and migration and immune escape abilities of DLBCL by regulation of PD-L1.


Asunto(s)
Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , MicroARNs/inmunología , ARN Largo no Codificante/inmunología , Escape del Tumor/genética , Apoptosis/fisiología , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Carcinogénesis , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Transformación Celular Neoplásica , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , Transducción de Señal , Escape del Tumor/inmunología
12.
Eur Biophys J ; 48(3): 249-260, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30783690

RESUMEN

The Love wave biosensor is considered to be one of the most promising probing methods in biomedical research and diagnosis, and has been applied to detect the mechano-biological behaviour of cells attached to the surface of the device. More efforts should be devoted to basic theoretical research and relevant device performance analysis that may contribute to the further developments of Love wave sensors. In this study, a 36º YX-LiTaO3-based Love wave sensor with a parylene-C wave guiding layer was adopted as a cell-based biosensor to monitor the adhesion process of tendon stem/progenitor cells (TSCs), a newly discovered cell type in tendons. A theoretical model is proposed to describe the Love wave propagation, in which the adherent cells are considered as a uniform viscoelastic layer. The effects of viscoelastic cell layer and wave guiding layer on the propagation velocity υ and propagation loss (PL) are investigated. The numerical results indicate that adherent cell layers of different storage or loss shear modulus in certain ranges can induce pronounced and characteristic variations in υ and PL, revealing the potential of Love wave sensors to provide useful quantitative measures on cellular mechanical properties. The sensor response to the adhesion of TSCs exhibits high consistency with experimental observations, which demonstrates the Love wave biosensor as a very promising sensor platform for investigating cellular activities under multiple physiological conditions.


Asunto(s)
Acústica , Técnicas Biosensibles/métodos , Adhesión Celular , Células Madre/citología , Tendones/citología , Elasticidad , Viscosidad
13.
Cancer Gene Ther ; 26(7-8): 195-207, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30470842

RESUMEN

Understanding the molecular mechanisms for the development of non-Hodgkin lymphoma (NHL) will improve our ability to cure the patients. qRT-PCR was applied for the examination of the efficiency of shRNA for DNMT1, the expression of suppressor genes, miRNA-152. The MTT analysis, cell cycle analysis, clonal formation, and apoptotic analysis were used to examine the functions of DNMT1 and miR-152 in lymphoma cells. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation of tumor suppressor genes. The dual luciferase assay and western blot were used to validate if DNMT1 is the target of miR-152. For the in vivo experiments, the lymphoma cells were injected into the nude mice for quantification of the tumor growth after transfection of miR-152 mimics. Knockdown of DNMT1 by shRNA (sh-DNMT1) in OCI-Ly10 and Granta-159 cells significantly upregulated the expression of tumor suppressor genes (SOCS3, BCL2L10, p16, p14, and SHP-1) via decreasing their methylation level. At the cellular level, we found sh-DNMT1 inhibited the proliferation, clonal formation and cell cycle progression and induced the cell apoptosis of lymphoma cells. Furthermore, we found miR-152 can downregulates the expression of DNMT1 via directly targeting the gene. Overexpression of miR-152 also increased the expression of tumor suppressor genes SOCS3 and SHP-1. And miR-152 also can inhibit the cell proliferation and induce the cell apoptosis. Moreover, we found overexpression of miR-152 significantly repressed the tumor growth with decreased DNMT1 expression and increased expression of tumor suppressor genes in vivo. Our study demonstrates that miR-152 can inhibit lymphoma growth via suppressing DNMT1-mediated silencing of SOCS3 and SHP-1. These data demonstrate a new mechanism for the development of NHL and this may provide a new therapeutic target for NHL.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 207: 96-104, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30212664

RESUMEN

Three new probes, named, [Cu(L1)2]Cl2 (C1), [Cu(L2)2]Cl2 (C2) and [Cu(L3)2]Cl2 (C3) were synthesized and well characterized. The probes C1, C2 and C3 were successfully achieved for the efficient detection of PO43- as turn-on fluorescence chemosensors in DMSO/H2O (v:v = 2:8, Tris-HCl pH = 7.20). The limit of detection (LOD) of probes C1, C2 or C3 for PO43- could be as low as 0.029 µM, 0.048 µM, 0.079 µM, respectively, which were effectively applied for the determination of the PO43- concentration in environmental water of swimming pool. What's more, the binding constant between probes C1, C2, C3 and PO43- are estimated to be 3.11 × 107 M-1 (R2 = 0.9992), 1.84 × 107 M-1 (R2 = 0.9956), 1.93 × 107 M-1 (R2 = 0.9976), respectively. The proposed mechanism for the "on-off-on" fluorescence response was confirmed by ESI-MS and fluorescence spectrum. Moreover, the membrane-permeable probe C1 was successfully demonstrated in monitoring of PO43- in cultured HepG2 cells.


Asunto(s)
Cobre/química , Colorantes Fluorescentes/química , Imagen Óptica/métodos , Fosfatos/análisis , Agua/análisis , Complejos de Coordinación/química , Células Hep G2 , Humanos , Límite de Detección , Microscopía Fluorescente/métodos , Espectrometría de Fluorescencia/métodos
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 211: 239-245, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30553147

RESUMEN

This work, two turn-on fluorescent probes (3-acetyl-2H-chromen-2-one (ACO) & (1E)-1-(1-(2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (CETC)) based on coumarin have been designed and synthesized, which could selectively and sensitively recognize ClO- with fast response time. ACO &CETC were almost non fluorescent possibly due to both the lacton form of coumarin and unbridged CN bonds which can undergo a nonradiative decay process in the excited state. Upon the addition of ClO-, ACO &CETC were oxidized to ring - opened by cleavage the CO and CN and the fluorescence intensity were increased considerably. Fluorescence titration experiments showed that the detection limit ACO &CETC is as low as 22 nm and 51 nm respectively. In particular, some relevant reactive species, including OH, 1O2, H2O2, KO2, some anions and cations cannot be interference with the test. In live cell experiments, ACO &CETC were successfully applied to image exogenous ClO- in HepG2 cells. Therefore, ACO &CETC not only could image ClO- in living cells but also proved that CO and CN can be cleavage by ClO-.


Asunto(s)
Benzopiranos/química , Colorantes Fluorescentes/química , Ácido Hipocloroso/análisis , Imagen Molecular/métodos , Semicarbacidas/química , Benzopiranos/síntesis química , Colorantes Fluorescentes/síntesis química , Células Hep G2 , Humanos , Oxidación-Reducción , Semicarbacidas/síntesis química , Sensibilidad y Especificidad , Espectrometría de Fluorescencia/métodos , Espectrofotometría Ultravioleta
16.
Am J Med Genet B Neuropsychiatr Genet ; 177(6): 589-595, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30076746

RESUMEN

Members of the neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3) encode important components of synaptic function implicated in autism and other neurodevelopmental/neuropsychiatric disorders. Loss of function variants have been reported predominantly in NRXN1, with fewer such variants detected in NRXN2 and NRXN3. Evidence for segregating NRNX3 variants has particularly been lacking. Here, we report identification by chromosomal microarray analysis of a rare exonic deletion affecting the NRXN3 alpha isoform in a three-generation Chinese family. The proband, a 7-year-old boy, presented with motor and language delay and met the clinical diagnostic criteria for autism. He also presented with moderate intellectual disability, attention-deficit hyperactivity disorder and facial dysmorphic features. The mother and maternal grandfather, both deletion carriers, presented with variable degrees of language and communication difficulties, as well as neuropsychiatric problems such as schizophrenia and temper tantrums. A compilation of sporadic cases with deletions involving part or all of NRXN3 revealed that 9 of 23 individuals (39%) displayed features of autism. The evidence for cosegregation in our family further supports a role for NRXN3 in autism and neurodevelopmental/neuropsychiatric disorders but demonstrates intrafamily variable expressivity due to this NRXN3 deletion, with schizophrenia and facial dysmorphism being potential novel features of NRXN3 haploinsufficiency.


Asunto(s)
Trastorno del Espectro Autista/genética , Proteínas del Tejido Nervioso/genética , Adulto , Grupo de Ascendencia Continental Asiática/genética , Trastorno Autístico/genética , Niño , China , Exones , Familia , Femenino , Eliminación de Gen , Heterocigoto , Humanos , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Masculino , Proteínas del Tejido Nervioso/metabolismo , Trastornos del Neurodesarrollo/genética , Pruebas Neuropsicológicas , Linaje , Isoformas de Proteínas , Eliminación de Secuencia , Secuenciación del Exoma Completo/métodos
17.
Mol Ther ; 26(9): 2255-2266, 2018 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-30017880

RESUMEN

Transforming growth factor ß1 (TGF-ß1) plays a promoting role in tumor growth via a mechanism associated with hyperactive Smad3 and suppressed Smad7 signaling in the tumor microenvironment. We report that retrieving the balance between Smad3 and Smad7 signaling with asiatic acid (AA, a Smad7 inducer) and naringenin (NG, a Smad3 inhibitor) effectively inhibited tumor progression in mouse models of invasive melanoma (B16F10) and lung carcinoma (LLC) by promoting natural killer (NK) cell development and cytotoxicity against cancer. Mechanistically, we found that Smad3 physically bound Id2 and IRF2 to suppress NK cell production and NK cell-mediated cytotoxicity against cancer. Treatment with AA and NG greatly inhibited Smad3 translation and phosphorylation while it restored Smad7 expression, and, therefore, it largely promoted NK cell differentiation, maturation, and cytotoxicity against cancer via Id2/IRF2-associated mechanisms. In contrast, silencing Id2 or IRF2 blunted the protective effects of AA and NG on NK cell-dependent anti-cancer activities. Thus, treatment with AA and NG produced an additive effect on inactivating TGF-ß1/Smad3 signaling, and, therefore, it suppressed melanoma and lung carcinoma growth by promoting NK cell immunity against cancer via a mechanism associated with Id2 and IRF2.


Asunto(s)
Flavanonas/farmacología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Triterpenos Pentacíclicos/farmacología , Proteína smad3/metabolismo , Proteína smad7/metabolismo , Animales , Western Blotting , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Factor 2 Regulador del Interferón/metabolismo , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos
18.
Cancer Immunol Res ; 6(8): 965-977, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29915022

RESUMEN

Natural killer (NK) cells, early effectors in anticancer immunity, are paralyzed by TGFß1, an immunosuppressive cytokine produced by cancer cells. Development and activity of NK cells are largely inhibited in the Smad3-dependent tumor microenvironment. Here, we used genetic engineering to generate a stable SMAD3-silencing human NK cell line, NK-92-S3KD, whose cancer-killing activity and cytokine production were significantly enhanced under TGFß1-rich condition compared with the parental cell line. Interestingly, we identified that the IFNG gene is a direct E4BP4 target gene. Thus, silencing of SMAD3 allows upregulation of E4BP4 that subsequently promoting interferon-γ (IFNγ) production in the NK-92-S3KD cells. More importantly, NK-92-S3KD immunotherapy increases the production of not only IFNγ, but also granzyme B and perforin in tumors; therefore, inhibiting cancer progression in two xenograft mouse models with human hepatoma (HepG2) and melanoma (A375). Thus, the NK-92-S3KD cell line may be useful for the clinical immunotherapy of cancer. Cancer Immunol Res; 6(8); 965-77. ©2018 AACR.


Asunto(s)
Inmunoterapia/métodos , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas Experimentales/terapia , Melanoma Experimental/terapia , Proteína smad3/genética , Animales , Línea Celular , Proteínas de la Matriz Extracelular/inmunología , Silenciador del Gen , Ingeniería Genética/métodos , Humanos , Interferón gamma/biosíntesis , Neoplasias Hepáticas Experimentales/inmunología , Melanoma Experimental/inmunología , Ratones Endogámicos NOD , Ratones Noqueados , Proteína smad3/inmunología , Factor de Crecimiento Transformador beta/inmunología , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 201: 216-222, 2018 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-29753966

RESUMEN

A fluorescence probe based on thiosemicarbazide has been synthesized and well characterized by 1H NMR, 13C NMR, Elemental analysis, Electrospray ionization mass spectra. The probe 1 functions as a multitarget ion sensor, detect biologically and ecologically important Cd2+, PO43- and Cr3+. Meanwhile, probe 1 displays selectivity for Cd2+ over other metal ions and anions in DMF by emission spectrum. Interestingly, probe 1 has been explored to recognize PO43- in CH3OH-H2O (v:v = 1:9). The binding stoichiometry of probe 1 with Cd2+ and PO43- are 2:1 and 1:1, respectively, which are confirmed by Electrospray ionization mass spectra. Probe 1 is selective, sensitive and reversibility/reusability to Cd2+ and PO43- with the detection limit as low as 0.035 µM and 0.011 µM respectively. Besides, the designed probe 1 has shown potential applications in the area of photo-printing.

20.
Eur J Med Genet ; 61(10): 607-611, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29654904

RESUMEN

Microdeletions at 11q13.1 are very rare. At present only two patients with 11q13.1 deletion involving neurexin 2 (NRXN2) have been reported. Both patients exhibited autistic features, which supported the role of NRXN2 in autism pathogenicity. It is currently unknown whether heterozygous deletion of NRXN2 is of high penetrance or if it is sufficient to result in autism behaviors. Here we reported a 2-year-9-month old boy with developmental delay, short stature, significant language delay and other congenital anomalies. In contrast to previously reported cases, the boy did not present with autistic behaviors and did not meet the clinical diagnosis of autism. A de novo 921 kb microdeletion at 11q13.1 was detected by chromosomal microarray analysis (CMA). Whole Exome Sequencing (WES) was also employed for our patient. The deletion was confirmed and no additional pathogenic variants were detected. We compared our patient's genomic information and clinical features with those of two previously reported individuals. Three patients shared similar deleted intervals and had similar clinical features except for autistic behaviors. This study suggested that NRXN2 gene had incomplete penetrance for autistic behavioral phenotype. The finding is of interest for genetic counseling and clinical management to patients with NRXN2 defects.


Asunto(s)
Trastorno Autístico/genética , Discapacidades del Desarrollo/genética , Proteínas del Tejido Nervioso/genética , Penetrancia , Eliminación de Secuencia , Preescolar , Cromosomas Humanos Par 11/genética , Discapacidades del Desarrollo/diagnóstico , Humanos , Desarrollo del Lenguaje , Masculino
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