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1.
Brain ; 146(8): 3373-3391, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36825461

RESUMEN

GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.


Asunto(s)
ADN Helicasas , ARN Helicasas , Humanos , Proteínas de Unión a Poli-ADP-Ribosa , Proteínas con Motivos de Reconocimiento de ARN , Regiones no Traducidas 5' , Cuerpos de Inclusión Intranucleares , Ribosomas , Expansión de Repetición de Trinucleótido/genética
2.
Parasitology ; 150(9): 821-830, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37395062

RESUMEN

In this study, the mitochondrial genome of Eulaelaps silvestris, which parasitizes Apodemus chevrieri, was sequenced and assembled to fill the gap in understanding the molecular evolution of the genus Eulaelaps. The E. silvestris mitochondrial genome is a double-stranded DNA molecule with a length of 14 882 bp, with a distinct AT preference for base composition and a notably higher AT content than GC content. The arrangement between genes is relatively compact, with a total of 10 gene intergenic regions and 12 gene overlap regions. All protein-coding genes had a typical ATN initiation codon, and only 2 protein-coding genes had an incomplete termination codon T. Out of the 13 protein-coding genes, the 5 most frequently used codons ended in A/U, with only 1 codon ending in G/C had an relative synonymous codon usage value >1. Except for trnS1 and trnS2, which lacked the D arm, all other tRNAs were able to form a typical cloverleaf structure; and there were a total of 38 mismatches in the folding process of tRNA genes. Unlike the gene arrangement order of the arthropod hypothetical ancestor, the E. silvestris mitochondrial genome underwent fewer rearrangements, mainly near tRNA genes and control regions. Both the maximum likelihood tree and the Bayesian tree showed that the family Haemogamasidae is most closely related to the family Dermanyssidae. The results not only provide a theoretical basis for studying the phylogenetic relationships of the genus Eulaelaps, but also provide molecular evidence that the family Haemogamasidae does not belong to the subfamily Laelapidae.


Asunto(s)
Genoma Mitocondrial , Animales , Filogenia , Teorema de Bayes , Secuencia de Bases , ARN de Transferencia/genética , Codón/genética , ARN Ribosómico/genética
3.
Exp Appl Acarol ; 90(3-4): 301-316, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37349609

RESUMEN

Some mites of the family Haemogamasidae can transmit a variety of zoonotic diseases and have important public health and safety implications. Currently, however, little attention has been paid to molecular data of Haemogamasidae species, limiting our understanding of their evolutionary and phylogenetic relationships. In this study, the complete mitochondrial genome of Eulaelaps huzhuensis was determined for the first time, and its genomic information was analyzed in detail. The mitochondrial genome of E. huzhuensis is 14,872 bp in length with 37 genes and two control regions. The base composition showed a distinct AT preference. Twelve protein-coding genes have a typical ATN as the start codon, and three protein-coding genes have incomplete stop codons. During the folding of tRNA genes, a total of 30 mismatches occurred, and three tRNA genes had an atypical cloverleaf secondary structure. The order of the E. huzhuensis mitochondrial genome arrangement is a new type of rearrangement in Mesostigmata. The phylogenetic analysis confirmed that the family Haemogamasidae is a monophyletic branch and does not belong to a subfamily of the Laelapidae. Our results lay the foundation for subsequent studies on the phylogeny and evolutionary history of the family Haemogamasidae.


Asunto(s)
Genoma Mitocondrial , Ácaros , Animales , ARN Ribosómico/genética , Filogenia , Ácaros/genética , ARN de Transferencia/genética
4.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1792-1799, 2023 Apr.
Artículo en Zh | MEDLINE | ID: mdl-37282953

RESUMEN

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.


Asunto(s)
Cardiopatías , Canales de Potasio , Humanos , Medicina Tradicional China , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Cardiopatías/tratamiento farmacológico , Iones
5.
Ann Rheum Dis ; 79(11): 1460-1467, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32737104

RESUMEN

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.


Asunto(s)
Antirreumáticos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Osteoporosis/epidemiología , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Humanos , Análisis de la Aleatorización Mendeliana
6.
Korean J Parasitol ; 58(2): 153-159, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32418384

RESUMEN

The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM=11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.


Asunto(s)
Vectores de Enfermedades , Tifus por Ácaros/parasitología , Trombiculidae , Animales , China/epidemiología , Interacciones Huésped-Parásitos , Ratas , Tifus por Ácaros/epidemiología
7.
Int J Neurosci ; 128(12): 1109-1113, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29962256

RESUMEN

AIM: Pantothenate-kinase-associated neurodegeneration (PKAN), which is characterised by iron accumulation in the basal ganglia, is a rare autosomal recessive neurodegenerative disorder caused by pantothenate kinase 2 (PANK2) gene mutations. The PANK2 gene is located on chromosome 20p13 and encodes pantothenate kinase. Herein, we identified one patient with PKAN who had mutations in the PANK2 gene. MATERIALS AND METHODS: We performed clinical and radiographic investigations, and diagnosed this disease at the clinical and genetic levels. RESULTS: It is worth mentioning that the patient displayed an eye-of-the-tiger sign. Through scanning the exons and flanking intronic sequences of PANK2 in patient and control subjects, we report a compound heterozygote c. 260A > G (NM_001324191) and c.405dupC (NM_153638) for PANK2 mutations in a Chinese patient with clinical manifestation of progressive prosopospasm, dysarthria and gait disturbance. Bioinformatics analysis showed that two variants exhibited highly conserved residues across species. CONCLUSION: we reported a patient presenting with atypical PKAN, and identified novel compound heterozygous PANK2 gene mutations..


Asunto(s)
Neurodegeneración Asociada a Pantotenato Quinasa/genética , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adulto , Pueblo Asiatico/genética , China , Femenino , Heterocigoto , Humanos , Masculino , Mutación , Linaje
8.
Mov Disord ; 31(12): 1905-1909, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27943471

RESUMEN

OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PD patients and controls. CONCLUSIONS: X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism. © 2016 International Parkinson and Movement Disorder Society.


Asunto(s)
Enfermedades de los Ganglios Basales/genética , Calcinosis/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedad de Parkinson/genética , Trastornos Parkinsonianos/genética , Proteínas de Unión al GTP rab/genética , Adulto , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Linaje
9.
Int J Neurosci ; 126(12): 1071-6, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26643368

RESUMEN

PURPOSE: Cerebral cavernous malformations (CCMs) are vascular anomalies predominantly in the central nervous system but may include lesions in other tissues, such as the retina, skin and liver. The main clinical manifestations include seizures, hemorrhage, recurrent headaches and focal neurological deficits. Previous studies of familial CCMs (FCCMs) have mainly reported in Hispanic and Caucasian cases. Here, we report on FCCMs in a Chinese family further characterized by a novel CCM1 gene mutation. MATERIALS AND METHODS: We investigated clinical and neuroradiological features of a Chinese family of 30 members. Furthermore, we used exome capture sequencing to identify the causing gene. The CCM1 mRNA expression level in three patients of the family and 10 wild-type healthy individuals were detected by real-time quantitative polymerase chain reaction (real-time RT-PCR). RESULTS: Brain magnetic resonance imaging demonstrated multiple intracranial lesions in seven members. The clinical manifestation of CCM was found in five of these cases, including recurrent headaches, weakness, hemorrhage and seizures. Moreover, we identified a novel nonsense mutation c.1159G>T (p. E387*) in the CCM1 gene in the pedigree. Based on real-time RT-PCR results, we have found that the CCM1 mRNA expression level in three patients was reduced by 35% than that in wild-type healthy individuals. CONCLUSIONS: Our finding suggests that the novel nonsense mutation c.1159G>T in CCM1 gene is associated with FCCM, and that CCM1 haploinsufficiency may be the underlying mechanism of CCMs. Furthermore, it also demonstrates that exome capture sequencing is an efficient and direct diagnostic tool to identify causes of genetically heterogeneous diseases.


Asunto(s)
Salud de la Familia , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Proteína KRIT1/genética , Mutación/genética , Adulto , Pueblo Asiatico , Análisis Mutacional de ADN , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Adulto Joven
10.
J Ethnopharmacol ; 330: 118264, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38692417

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.


Asunto(s)
Apoptosis , Medicamentos Herbarios Chinos , Ferroptosis , Insuficiencia Cardíaca , Miocitos Cardíacos , Transducción de Señal , Animales , Masculino , Ratas , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Ferroptosis/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Polvos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética
11.
Mol Cell Biochem ; 382(1-2): 253-61, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23797321

RESUMEN

Macrophage apoptosis is a prominent feature of advanced atherosclerotic plaques. Here, we examined the hypothesis that the apoptotic machinery is regulated by microRNA-155 (miR-155). Constitutive expression of miR-155 was detected in RAW264.7 cells, which was increased following stimulation with oxidized low-density lipoprotein (OxLDL) in a dose- and time-dependent manner. OxLDL-treated RAW264.7 cells showed a marked time- and dose-dependent increase in apoptosis, which was suppressed in the presence of mimics and increased with antagonists of miR-155. Bioinformatics analysis revealed Fas-associated death domain-containing protein (FADD) as a putative target of miR-155. Luciferase reporter assay and Western blot further disclosed that miR-155 inhibits FADD expression by directly targeting the 3'-UTR region. We propose that miR-155 attenuates the macrophage apoptosis, at least in part, through FADD regulation, since forced expression of FADD blocked the ability of miR-155 to inhibit apoptosis. Our results collectively suggest that miR-155 attenuates apoptosis of OxLDL-mediated RAW264.7 cells by targeting FADD, supporting a possible therapeutic role in atherosclerosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Lipoproteínas LDL/farmacología , Macrófagos/citología , Macrófagos/metabolismo , MicroARNs/metabolismo , Regiones no Traducidas 3'/genética , Animales , Apoptosis/genética , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Citoprotección/efectos de los fármacos , Citoprotección/genética , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones , MicroARNs/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
12.
Stem Cell Res Ther ; 14(1): 273, 2023 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-37759328

RESUMEN

BACKGROUND: Identification of promising targeted antigens that exhibited cancer-specific expression is a crucial step in the development of novel antibody-targeted therapies. We here aimed to investigate the anti-tumor activity of a novel monoclonal antibody (mAb) 11C9 and identify the antibody tractable target in the hepatocellular cancer stem cells (HCSCs). METHODS: The identification of the targeted antigen was conducted using SDS-PAGE, western blot, mass spectrometry, and co-immunoprecipitation. Silence of HSP90 was induced by siRNA interference. Positive cells were sorted by fluorescence-activated cell sorting. Double-immunofluorescent (IF) staining and two-color flow cytometry detected the co-expression. Self-renewal, invasion, and drug resistance were assessed by sphere formation, matrigel-coated Transwell assay, and CCK-8 assay, respectively. Tumorigenicity was evaluated in mouse xenograft models. RNA-seq and bioinformatics analysis were performed to explore the mechanism of mAb 11C9 and potential targets. RESULTS: MAb 11C9 inhibited invasion and self-renewal abilities of HCC cell lines and reversed the cisplatin resistance. HSP90 (~ 95 kDa) was identified as a targeted antigen of mAb 11C9. Tissue microarrays and online databases revealed that HSP90 was overexpressed in HCC and associated with a poor prognosis. FACS and double-IF staining showed the co-expression of HSP90 and CSCs markers (CD90 and ESA). In vitro and in vivo demonstrated the tumorigenic potentials of HSP90. The inhibition of HSP90 by siRNA interference or 17-AAG inhibitor both decreased the number of invasion, sphere cells, and CD90+ or ESA+ cells, as well as reversed the resistance. Bioinformatics analysis and western blot verified that HSP90 activated Wnt/ß-catenin signaling. CONCLUSIONS: The study preliminarily revealed the anti-tumor activity of mAb 11C9. More importantly, we identified HSP90 as a targeted antigen of mAb 11C9, which functions as an oncogene in phenotype shaping, stemness maintenance, and therapeutic resistance by activating Wnt/ß-catenin signaling.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , beta Catenina/metabolismo , Línea Celular Tumoral , ARN Interferente Pequeño/metabolismo , Modelos Animales de Enfermedad , Células Madre Neoplásicas/metabolismo , Proliferación Celular
13.
ACS Nano ; 16(3): 3664-3673, 2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35166113

RESUMEN

We propose a universal strategy to 3D printing the graphene oxide (GO) complex structure with GO highly aligned and densely compacted, by the combination of direct ink writing and constrained drying. The constraints not only allow the generation of a huge capillary force accompanied by water evaporation at nanoscale, which induces the high compaction and alignment of GO, but also limit the shrinkage of the extruded filaments only along the wall thickness direction, therefore, successfully maintaining the uniformity of the structure at macroscale. We discover that the shrinkage stress gradually increased during the drying process, with the maximum exceeding ∼0.74 MPa, significantly higher than other colloidal systems. Interestingly, because of the convergence between plates with different orientations of the constraints, a gradient of porosity naturally formed across the thickness direction at the corner. This allows us to 3D print humidity sensitive GO based soft robotics.

14.
Neuron ; 55(2): 247-60, 2007 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-17640526

RESUMEN

Agrin induces, whereas acetylcholine (ACh) disperses, ACh receptor (AChR) clusters during neuromuscular synaptogenesis. Such counteractive interaction leads to eventual dispersal of nonsynaptic AChR-rich sites and formation of receptor clusters at the postjunctional membrane. However, the underlying mechanisms are not well understood. Here we show that calpain, a calcium-dependent protease, is activated by the cholinergic stimulation and is required for induced dispersion of AChR clusters. Interestingly, the AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease activity of calpain. Disrupting the endogenous rapsyn/calpain interaction enhanced CCh-induced dispersion of AChR clusters. Moreover, the loss of AChR clusters in agrin mutant mice was partially rescued by the inhibition of calpain via overexpressing calpastatin, an endogenous calpain inhibitor, or injecting calpeptin, a cell-permeable calpain inhibitor. These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity.


Asunto(s)
Agrina/metabolismo , Calpaína/metabolismo , Proteínas Musculares/metabolismo , Unión Neuromuscular/metabolismo , Agregación de Receptores/fisiología , Receptores Colinérgicos/metabolismo , Animales , Proteínas de Unión al Calcio/metabolismo , Carbacol/farmacología , Línea Celular , Agonistas Colinérgicos/farmacología , Humanos , Ratones , Ratones Transgénicos , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Unión Neuromuscular/efectos de los fármacos , Agregación de Receptores/efectos de los fármacos , Receptores Colinérgicos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Membranas Sinápticas/efectos de los fármacos , Membranas Sinápticas/metabolismo
15.
Parasitol Res ; 108(5): 1243-51, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21140167

RESUMEN

Understanding factors that shape host selection has been a classic issue in ecology, evolutionary biology, and epidemiological investigation. During the survey from 2000 to 2009, a total of 11,216 individuals of small mammals were captured from Yunnan Province in southwestern China. The captured small mammalian hosts belong to five orders, ten families, 35 genera, and 65 species and from their body surface, 38,885 individuals of ectoparasitic sucking lice were collected, which represent five families, seven genera, and 31 species. Based on niche overlap of dominant sucking lice on their primary hosts, we used hierarchical cluster analysis to sort different sucking louse species' resource utilizations of similar kind into respective categories. Given λ<5, there are only two groups clustered, however, sucking louse species' resource utilization was sorted into eight respective categories at λ=15. The results revealed that most species of sucking lice usually had high host specificity and a certain species of sucking louse usually restricted to one or few small mammalian species as their dominant hosts. Correspondence analysis was used to visualize associations between parasitic sucking lice and their small mammalian hosts, which suggested three different patterns of host resource utilization: species specialists, genera generalists, and multiple selections. For example, Sathrax durus (Johnson) only parasitized on species of Tupaia belangeri (Wagner), Hoplopleura edentula (Fahredholz) predominatly on genus of Eothenomys, and Polyplax reclinata (Nitzsch) on Family of Soricidae. Our results demonstrate that sucking lice have high host specificity and this might be due to coevolution between sucking lice and their hosts.


Asunto(s)
Anoplura/fisiología , Anoplura/patogenicidad , Infestaciones Ectoparasitarias/parasitología , Mamíferos/parasitología , Animales , Conducta Animal , China , Análisis por Conglomerados
16.
Zhonghua Fu Chan Ke Za Zhi ; 46(2): 113-8, 2011 Feb.
Artículo en Zh | MEDLINE | ID: mdl-21426769

RESUMEN

OBJECTIVE: To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA(125) in detecting and monitoring ovarian cancer. METHODS: Circulating IgG, IgM autoantibodies against ovarian cancer associated antigens which included TM4SF1, C1D, TIZ, OV-142, FXR1 and OV-189 were measured by indirect ELISA in serum from 126 patients with ovarian cancer (prior treatment), 42 patients with benign ovarian masses, 142 healthy women. Cut off value of IgG, IgM autoantibodies were determined by receive operating characteristic (ROC) curve. CA(125) was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum), combining autoantibody spectrum with CA(125) by binary logistic regresion. The positive ratio of autoantibody spectrum in serum (prior and post treatment) of 24 synchronization patients with ovarian cancer was analyzed to evaluate the value in monitoring state of illness. RESULTS: Our data indicated that serum contains IgG, IgM autoantibodies against ovarian cancer associated antigens. The positive ratio of IgG autoantibodies in serum from ovarian cancer patients and cancer-free patients were 34.1% - 47.6% and 13.0% - 19.0%, respectively (P < 0.05). The positive ratio of IgM autoantibodies in serum from ovarian cancer patients and cancer-free patients were 39.7% - 53.2% and 12.0% - 33.2%, respectively (P < 0.05). The positive ratio of IgG autoantibodies against FXR1 and IgM autoantibodies against TIZ, FXR1 and OV-189 in early stage (I-II) ovarian cancer (55.3%, 63.8%, 61.7% and 66.0%) were significantly higher than those in advanced (III-IV) ovarian cancer (34.2%, 39.2%, 26.6%, 45.6%; all P < 0.05). Combining five autoantibodies (TM4SF1 IgG, TM4SF1 IgM, C1D IgG, FXR1 IgG and TIZ IgM) showed significantly improved sensitivity (75.4%, P < 0.05), lower specificity (78.3%, P < 0.05) and similar accuracy (77.1%, P > 0.05) in detecting ovarian cancer compared to those of CA(125) (61.1%, 88.0%, 77.1%). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76.6%), compared to those of CA(125) (51.1%, P < 0.05). Combining autoantibody spectrum with CA(125) showed significantly improved sensitivity (85.7%), specificity (90.8%)and accuracy (88.7%) in detecting ovarian cancer compared to those of autoantibody spectrum alone (all P < 0.05), while CA(125) (61.1%, P < 0.05; 88.0%, P > 0.05; 77.1%, P < 0.05). The positive ratio of combine the autoantibody spectrum with CA(125) was significantly lower in 24 post-treatment serum (42%) compared to the pairing prior treatment serum (88%, P < 0.05). CONCLUSION: Combining the autoantibody spectrum against ovarian cancer associated antigens with CA(125) can improve sensitivity, specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.


Asunto(s)
Autoanticuerpos/sangre , Antígeno Ca-125/sangre , Neoplasias Ováricas/diagnóstico , Adolescente , Adulto , Anciano , Antígenos de Neoplasias/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Persona de Mediana Edad , Estadificación de Neoplasias , Enfermedades del Ovario/sangre , Enfermedades del Ovario/diagnóstico , Enfermedades del Ovario/inmunología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/inmunología , Sensibilidad y Especificidad , Adulto Joven
17.
Artículo en Zh | MEDLINE | ID: mdl-22356714

RESUMEN

OBJECTIVE: To explore the toxic effects of lead acetate on the apoptosis and ultrastructure of human renal tubular epithelial cells (HK-2). METHODS: After HK-2 cells were exposed to 5, 10 and 20 µmol/L lead acetate for 24 h, the morphological changes of HK-2 cells were observed by Hochest 33342-PI staining, and the ultrastructure changes of HK-2 cells were examined under a electron microscope, LDH activity and MDA content in supernatant of HK-2 cellular culture were detected by spectrophotometer, DNA damage of HK-2 was determined by DNA ladder and the apoptotic rates of HK-2 cells were measured by flow cytometry. RESULTS: The morphological changes of apoptotic HK-2 cells in exposure group were observed by Hochest 33342-PI staining. The cytoplasm vacuoles, karyopycnosis, nuclear membrane vague and apoptotic bodies in HK-2 cells of exposure group were found under electron microscopy. LDH activity and MDA contents in exposure group increased significantly, as compared to control group (P < 0.01). The results of DNA Ladder showed that DNA damage of HK-2 cells in exposure group appeared. The apoptotic rates of HK-2 cells exposed to 5, 10, 20 µmol/L lead acetate were 14.16% ± 2.94%, 19.45% ± 2.73%, 25.01% ± 3.97%, respectively, which were significantly higher than that (5.81% ± 2.18%) in control group (P < 0.05). CONCLUSION: Lead acetate could remarkably induce the apoptosis of HK-2 cells and affect the kidney.


Asunto(s)
Apoptosis/efectos de los fármacos , Células Epiteliales , Túbulos Renales Proximales , Compuestos Organometálicos/toxicidad , Línea Celular , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Humanos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/ultraestructura
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 490-494, 2021 Sep.
Artículo en Zh | MEDLINE | ID: mdl-34816659

RESUMEN

Objective: To investigate the effects of RPA1 silencing on the invasion, migration and cell cycle of human nasopharyngeal carcinoma CNE-2R cells. Methods: shRNA technology was used to construct CNE-2R cell lines with RPA1 low-expression, which were verified by RT-PCR and Western blotting. The following assays were performed using the three 3 groups: control group(CNE-2),negative control group(NC-shRNA) and RPA1 down-regulation group(RPA1-shRNA). The effects of RPA silence on the proliferation, invasion, migration, and cell cycle of CNE-2R cells were detected using Cell Counting Kit-8, clone formation experiment, Transwell, scratch test and flow cytometry, respectively. The expressions of Chk2, p-Chk2, Cdc 25c and p-cdc25c were tested by Western blot assay. Results: The expressions of RPA1 mRNA and protein in the RPA1-shRNA group were lower than those in the CNE-2 and NC-shRNA groups significantly (P<0.01 and 0.05). Compared with CNE-2 and NC-shRNA groups, the abilities of proliferation, invasion and migration of RPA1-shRNA group were decreased and the cell cycle in the RPA1-shRNA group was blocked in the G2/M phase (P<0.01). The expressions of Chk2 and Cdc25c in RPA1-shRNA group cells were lower than those in CNE-2R and NC-shRNA group cells (P<0.05), while the expressions of p-Chk2 and p-cdc25c were higher than those in the other groups (P<0.05). Conclusion: After RPA1 silenced, the proliferation and migration of radio resistant human nasopharyngeal carcinoma CNE-2R cells was inhibited, resulting in cell cycle arrested in the G2/M phase.


Asunto(s)
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteína de Replicación A/genética , Apoptosis , Ciclo Celular , División Celular , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Silenciador del Gen , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética
19.
Cell Death Discov ; 7(1): 282, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34635641

RESUMEN

The fatality rate of non-small cell lung cancer (NSCLC) has been high due to the existence of cancer stem cells (CSCs). Non-muscle myosin heavy chain 9 (MYH9) can promote the progression of various tumors, but its effect on the stem cell-like characteristics of lung cancer cells (LCCs) has not been clarified. Our research found that the stemness characteristics of LCCs were significantly enhanced by the overexpression of MYH9, and the knockout of MYH9 had the opposite effects. The in vivo with inhibitor blebbistatin further confirmed the effect of MYH9 on the stem cell-like behavior of LCCs. Furthermore, western blotting showed that the expression level of CSCs markers (CD44, SOX2, Nanog, CD133, and OCT4) was also regulated by MYH9. Mechanistic studies have shown that MYH9 regulates stem cell-like features of LCCs by regulating the mTOR signaling pathway, which was supported by sphere formation experiments after LCCs were treated with inhibitors Rapamycin and CHIR-99021. Importantly, high expression of MYH9 in lung cancer is positively correlated with poor clinical prognosis and is an independent risk factor for patients with NSCLC.

20.
Stem Cell Res Ther ; 12(1): 119, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579362

RESUMEN

BACKGROUND: Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. METHODS: Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. RESULTS: Targeted antigen showed a surface antigen expression pattern, and the 43-55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. CONCLUSIONS: ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7.


Asunto(s)
Neoplasias , Fosfopiruvato Hidratasa , Proteínas Quinasas Activadas por AMP , Anticuerpos Monoclonales , Biomarcadores de Tumor , Línea Celular Tumoral , Pulmón , Células Madre Neoplásicas , Fenotipo , Fosfopiruvato Hidratasa/genética , Serina-Treonina Quinasas TOR/genética
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