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Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.
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Enfermedades Neurodegenerativas , ARN Circular , Humanos , ARN Circular/genética , Enfermedades Neurodegenerativas/genética , ARN/genética , Envejecimiento/genética , EncéfaloRESUMEN
DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.
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Metilación de ADN , Predisposición Genética a la Enfermedad , Bovinos , Animales , Epigénesis Genética , Enfermedades de los Bovinos/genética , Complejo Respiratorio Bovino/genéticaRESUMEN
Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Ácido Tióctico , Animales , Ratones , Ratas , beta Catenina/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Transición Epitelial-Mesenquimal , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Glucosa/metabolismo , Riñón/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Receptor alfa X Retinoide/efectos de los fármacos , Receptor alfa X Retinoide/metabolismoRESUMEN
BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.
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Síndrome Hipereosinofílico , Hepatopatías , Trombosis , Masculino , Humanos , Niño , Vena Porta/diagnóstico por imagen , Vena Esplénica/diagnóstico por imagen , Venas Mesentéricas/diagnóstico por imagen , Trombosis/etiología , Síndrome Hipereosinofílico/complicaciones , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/tratamiento farmacológicoRESUMEN
The aim of this study was to investigate the selection signatures at a genome-wide level in 'Pishan' sheep using Specific Locus Amplified Fragment (SLAF)-seq. Blood samples from 126 ewes were sequenced using SLAF tags, and the ovarian tissues from 8 ewes (Bashbay sheep, a single litter size group (SG group); 'Pishan' sheep, double litter size group (DG group)) were collected to detect expression levels by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Selection signature analysis was performed using global fixation index (Fst) and nucleotide diversity (π) ratio. A total of 1,192,168 high-quality SLAFs were identified. Notably, 2380 candidate regions under selection using two approaches were identified. A total of 2069 genes were identified, which were involved in dopaminergic synapses, thyroid hormone synthesis, ovarian steroidogenesis and thyroid hormone signalling pathways. Furthermore, Growth Differentiation Factor 9 (GDF9), Period Circadian Regulator 2 (PER2), Thyroid Stimulating Hormone Receptor (TSHR), and Nuclear Receptor Coactivator 1 (NCOA1) reside within these regions and pathways. The expression levels of GDF9 and PER2 genes in sheep tissue of the DG group were significantly higher than those in the SG group. These genes are interesting candidates for litter size and provide a starting point for further identification of conservation strategies for 'Pishan' sheep.
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Polimorfismo de Nucleótido Simple , Hormonas Tiroideas , Embarazo , Ovinos/genética , Animales , Femenino , Tamaño de la Camada/genética , Secuencia de BasesRESUMEN
Donkey milk has high nutritional and medicinal value, but there are few researches in donkey milk traits, especially on genome. The whole lactation of 89 donkeys was recorded and it was found that Xinjiang donkey had good lactation performance while great differences among individuals. In our previous study, four genes including LGALS2, NUMB, ADCY8 and CA8 were identified as milk-associated with Chinese Kazakh house, based on Equine 670k Chip genomic analysis. And then 15 SNPs of the four key genes were conducted for genotyping in Xinjiang donkey in this study, one of Chinese indigenous breed, 14 SNPs were successful classified. And those SNPs were correlation analysis with milk yield of Xinjiang donkeys. The results showed that NUMB g.46709914T > G was significantly correlated with daily milk yield of Xinjiang donkey in the early, middle, and late periods, while ADCY8 g.48366302T > C, CA8 g.89567442T > G and CA8 g.89598328T > A were significantly correlated with lactation in the late periods. These results indicate that NUMB g.46709914T > G can be as markers of candidate genes for lactating traits in donkeys, SNPs of ADCY8 and CA8 as potential. Our findings will not only help confirm key genes for donkey milk traits, but also provide future for genomic selection in donkeys.
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Equidae , Leche , Femenino , Caballos , Animales , Equidae/genética , Lactancia/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
LncRNAs have recently received special attention due to their critical role in many important biological processes. There are few reports on its regulatory function in sheep fat deposition. In this study, two sheep populations with different tail types in Xinjiang, Bashibai sheep (fat-tailed) and the hybrid population of Bashibai sheep and wild argali (small-tailed) were selected for whole transcriptome sequencing from their tail tissues. First, 728 differentially expressed LncRNAs of tail fat between Bashibai and F2 sheep were identified by RNA-seq. Second, the tissue expression profile and relative expression difference between Bashibai and F2 sheep of 2 of 728 DE LncRNAs were analyzed by RT-PCR. LncRNA-MSTRG.24995 was highly expressed in tail fat, while lncRNA-MSTRG.36913 was highly expressed in subcutaneous fat. In addition, the expressions of LncRNA-MSTRG.24995 and LncRNA-MSTRG.36913 in tail fat of F2 sheep were significantly lower than that of Bashibai sheep, while those patterns in longissimus dorsi, quadriceps femoris and rumen were reversed. Third, the expression pattern of target genes FASN and THRSP in each tissue was similar with that of corresponding LncRNAs. The LncRNA-MSTRG.24995 directly affects tail fat deposition by FASN gene, while the LncRNA-MSTRG.36913 indirectly affects that by THRSP gene. This will help us to understand molecular mechanism of fat tail deposition from transcriptomic perspectives.
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ARN Largo no Codificante , Animales , Ovinos/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cola (estructura animal) , Perfilación de la Expresión Génica/veterinaria , Transcriptoma/genética , RNA-SeqRESUMEN
This study determined the surface electromyography (sEMG) characteristics of healthy Chinese adults during swallowing to provide a reference for the clinical differential diagnosis of swallowing and dysphagia. sEMG was performed on 187 healthy adults to obtain quantitative information on normal pharyngeal swallowing. The evaluated parameters included the timing and amplitude of sEMG activity in the submental and infrahyoid muscles. A normative database was constructed for the timing and amplitude of muscle activity during pharyngeal swallowing. Results indicated that the duration of sEMG activity was related to the age of the patient; the duration gradually increasing with age. Similarly, the duration of the sEMG activity was associated with the type of swallowing. The duration of the sEMG activity was similar for dry and wet swallowing but was significantly different for excessive swallowing. The mean amplitude of sEMG activity for the submental and infrahyoid muscles was not significantly associated with patient age. A significant correlation between the mean amplitude of sEMG activity and the types of normal swallowing was observed in infrahyoid, but not in submental muscle activity. This study is the first report on the establishment of a normative database for the duration and amplitude of muscle activity based on sEMG analysis of pharyngeal swallowing in healthy Chinese adults.
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Trastornos de Deglución , Deglución , Adulto , Humanos , Deglución/fisiología , Electromiografía/métodos , Pueblos del Este de Asia , Trastornos de Deglución/diagnóstico , Músculos del CuelloRESUMEN
This Fructus,study including and aimed to construct a rapid and nondestructive detection flavonoid,model betaine,for and of the content vitamin of(Vit four four quality C).index components Lycium barbarum polysaccharide,of inL ycii rawma total and C Hyperspectral data quantitative of terials modelswere powder developed Lycii using Fructus partial were squares effects collected,regression raw based LSR),on the support content vector the above components,the forest least(P regression compared,(SVR),the and effects random three regression(RFR)were algorithms.also The Four spectral predictive commonly data of the materialsand powder were were applied and of spectral quantitative for models reduction.compared.used were pre-processing screened methods feature to successive pre-process projection the raw algorithm data(SPA),noise competitive Thepre-processed for bands using adaptive reweigh ted sampling howed(CARS),the and maximal effects relevance based and raw minimal materials redundancy and(MRMR)were algorithms Following to optimize multiplicative the models.scatter The correction Based resultss(MS that prediction SPA on feature the powder prediction similar.PLSR C)denoising sproposed and integrated for model,screening the the coefficient bands,determination the effect(R_C~2)of(MSC-SPA-PLSR)coefficient was optimal.of on(R_P~2)thi of of calibration flavonoid,and and of all determination greater prediction0.83,L.barbarum inconte nt prediction of polysaccharide,total mean betaine,of Vit C were than smallest In the compared study,root with mean other prediction content squareserror models of the calibration(RMSEC)residual and deviation root squares was error2.46,prediction2.58,(RMSEP)and were the,and prediction(RPD)2.50,developed3.58,achieve respectively.rapid this the the quality mod el(MSC-SPA-PLSR)fourcomponents based Fructus,on hyperspectral which technology was approach to rapid and effective detection detection of the of Lycii in Lycii provided a new to the and nondestructive of of Fructus.
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Betaína , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Polvos , Análisis de los Mínimos Cuadrados , Algoritmos , FlavonoidesRESUMEN
INTRODUCTION: Reducing the delay in time to primary percutaneous coronary intervention (PCI) for acute coronary syndrome patients in the non-urban emergency department (ED) is of critical importance. Conventionally, physicians in a non-PCI-capable, non-urban local emergency department (LED) require approval from a tertiary university hospital emergency department (TUH-ED) prior to transferring eligible STEMI patients for PCI procedures. To reduce the ED delay time, this study developed a direct connection between the LED and the cardiac catheterisation laboratory in the TUH (TUH cath lab). METHODS: ST-elevation myocardial infarction (STEMI) patients' medical records for 2014 to 2017, from a non-PCI regional hospital located in one of the rural counties in central Taiwan and a TUH-ED in a metropolitan area in the centre of Taiwan, were retrospectively collected and classified into two categories: the LED referral (group A) and the TUH-non-referral (group B). This study compared the ED delay time between TUH non-referral patients in the TUH and LED referral patients in the LED, to determine whether a direct connection reduces current LED delay time. RESULTS: A total of 214 patients (group A, n=62; group B, n=152) who underwent PCI procedures at the TUH were enrolled in the study. ED delay times in the LED were significantly less than the TUH-ED (45.0 v 66.0 min, p<0.01.) Conclusion: The direct connection between the LED and the TUH cath lab effectively shortened the ED delay time in the LED, allowing for earlier primary PCI procedures for the transferred STEMI patients.
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Transferencia de Pacientes/organización & administración , Intervención Coronaria Percutánea/métodos , Servicios de Salud Rural/organización & administración , Infarto del Miocardio con Elevación del ST/cirugía , Tiempo de Tratamiento/organización & administración , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital/organización & administración , Femenino , Humanos , Relaciones Interinstitucionales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán , Factores de TiempoRESUMEN
Single atom catalysts (SACs) with the maximized metal atom efficiency have sparked great attention. However, it is challenging to obtain SACs with high metal loading, high catalytic activity, and good stability. Herein, we demonstrate a new strategy to develop a highly active and stable Ag single atom in carbon nitride (Ag-N2 C2 /CN) catalyst with a unique coordination. The Ag atomic dispersion and Ag-N2 C2 configuration have been identified by aberration-correction high-angle-annular-dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and extended X-ray absorption. Experiments and DFT calculations further verify that Ag-N2 C2 can reduce the H2 evolution barrier, expand the light absorption range, and improve the charge transfer of CN. As a result, the Ag-N2 C2 /CN catalyst exhibits much better H2 evolution activity than the N-coordinated Ag single atom in CN (Ag-N4 /CN), and is even superior to the Pt nanoparticle-loaded CN (PtNP /CN). This work provides a new idea for the design and synthesis of SACs with novel configurations and excellent catalytic activity and durability.
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Genome-wide association study (GWAS) identified chromosome 12p13 rs12425791 and rs11833579 as susceptibility loci of ischemic stroke (IS) in a European population. However, conflicting results were obtained in subsequent replication analysis. miR-200c, located on chromosome 12p13, was found to have a neuroprotective effect on ischemia. Our aim of this study was to investigate the association of the rs12425791, rs11833579 and rs12904 in the binding site of miR-200c with the risk of IS. The rs12425791, rs11833579, and rs12904 were genotyped using a TaqMan allelic discrimination assay. The results were verified by Sanger sequencing. We found that the rs12904 AG/GG genotypes and G allele were associated with a decreased risk of IS (AG/GG vs. AA: adjusted OR = 0.64; 95% CI, 0.44-0.95; G vs. A: adjusted OR = 0.65; 95% CI, 0.46-0.93). The combined genotypes of the rs11833579AG/AA and rs12904AG/GG were also associated with a reduced risk of IS (OR = 0.65; 95% CI, 0.46-0.93). These findings suggest that the rs12904 may have a jointly protective effect against the risk of IS.
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Isquemia Encefálica/genética , Predisposición Genética a la Enfermedad , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Accidente Cerebrovascular/genética , Sitios de Unión , Cromosomas Humanos Par 12/genética , Femenino , Estudio de Asociación del Genoma Completo , Haplotipos/genética , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Factores de RiesgoRESUMEN
AIM: To investigate whether the skin barrier function is impaired with regard to the pH value, water content, transepidermal water loss (TEWL), and the integrity of the stratum corneum, and whether the expression of caspase-14 is altered in moderate to severe chronic hand eczema (CHE). METHODS: Thirty patients with moderate to severe CHE treated at our institute and 30 healthy volunteers were included in this study. The pH value, water content, TEWL, and the integrity of the stratum corneum were measured in all subjects. RESULTS: Significantly increased pH value, decreased water content, elevated TEWL, and impaired integrity of the stratum corneum were observed in the lesional skin of CHE patients compared with the nonlesional skin of CHE patients and the normal skin of healthy volunteers. The expression of caspase-14 decreased in the lesional and nonlesional skin of CHE patients compared with the normal skin of healthy volunteers, especially prominent in the nonlesional skin. The mean optical density (OD) value of immunohistochemical staining for caspase-14 was significantly lower in the nonlesional skin than in the lesional skin and normal skin (p < 0.01 for both). Although the mean OD value was lower in the lesional skin than in the normal skin, the difference was not statistically significant (p > 0.05). CONCLUSION: Skin barrier dysfunction indeed occurs in CHE patients, which may be related to mechanisms associated with a downregulated expression of caspase-14.
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Caspasa 14/metabolismo , Eccema/enzimología , Epidermis/fisiopatología , Dermatosis de la Mano/enzimología , Adulto , Anciano , Regulación hacia Abajo , Eccema/fisiopatología , Epidermis/química , Femenino , Dermatosis de la Mano/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Fenómenos Fisiológicos de la Piel , Agua/metabolismo , Pérdida Insensible de AguaRESUMEN
OBJECTIVE: To study serologic and gene characteristics of the B(A) blood group of blood donation volunteers in Jilin Province, China. METHODS: ABO subgroups were identified by standard serologic techniques in ABO typing discrepancy samples from all donors at the Jilin Blood Center (410,354 non-repeat donors). DNA (deoxyribonucleic acid) was collected from each sample and PCR (polymerase chain reaction) was used to sequence exons 6 and 7 and intron 6, part 5 from the ABO subgroup samples. PCR products were sequenced to identify ABO subgroups and the B(A) allele. RESULTS: Four cases of B(A) blood type were found after sequencing, including two different alleles: B(A)02 and B(A)04. Three of the four alleles were B(A)04. CONCLUSION: Among blood donation volunteers in Jilin Province, China, B(A)04 is the most common B(A) blood group allele, followed by B(A)02. The B(A) blood group is associated with a complicated serologic phenotype and DNA detection is necessary for this atypical phenotype sample.
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Sistema del Grupo Sanguíneo ABO/genética , Adulto , Alelos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Chronic myelogenous leukemia (CML) is a hematological stem cell disorder. Tyrosine kinase inhibitors (TKIs) are the standard treatments for CML, but a number of patients fail to respond effectively due to gene mutations. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been shown to have anti-tumor effect on solid tumor whereas the anti-CML effect and its underlying mechanism have not been completely elucidated. METHODS: The cytotoxic effects of celecoxib and/or imatinib were evaluated by MTT assay. Cell cycle distribution was examined by propidium iodide (PI) assay. Apoptosis or necrosis was analyzed by Annexin-V/PI, Hoechst 33342 staining and Western blot assays. Autophagy suppression effect of celecoxib was examined by Western blot and LysoTracker probe labelling. Lysosensor probe labelling was used to detect the effect of celecoxib on the lysosomal function. RESULTS: In this study, we found that celecoxib had therapy efficacy in KBM5 and imatinib-resistant KBM5-T315I CML cell lines. Celecoxib caused significant cytotoxic effect in both cell lines, especially in KBM5-T315I cells exposed to celecoxib for 72 h. Moreover, celecoxib induced necrosis and apoptosis while inhibited autophagy in CML cell lines and patient samples. Furthermore, this study demonstrated that celecoxib prevented the autophagic flux by inhibiting lysosome function. Celecoxib was tested in combination with imatinib, demonstrating that celecoxib could strengthen the cytotoxicity of imatinib in imatinib-resistant CML cells. CONCLUSIONS: These findings showed that celecoxib had therapy efficacy on CML cells. And it is first time to demonstrate that celecoxib is an autophagy suppresser and a combination of celecoxib and imatinib might be a promising new therapeutic strategy for imatinib-resistant CML cells.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Celecoxib/farmacología , Celecoxib/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Adulto , Línea Celular Tumoral , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Mesilato de Imatinib/farmacología , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Persona de Mediana Edad , Necrosis , Estadificación de NeoplasiasRESUMEN
BACKGROUND/AIM: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. METHODS: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. RESULTS: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. CONCLUSION: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.
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Apoptosis/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Leucemia Mieloide Aguda/patología , Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Regulación hacia Arriba , Secuencia de Bases , Western Blotting , Caspasa 8/metabolismo , Regulación hacia Abajo , Resistencia a Antineoplásicos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Interferencia de ARN , Sirolimus/farmacologíaRESUMEN
BACKGROUND: The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. METHODS: The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. RESULTS: HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. CONCLUSIONS: Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity.
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Carcinogénesis , Carcinoma Hepatocelular/genética , Epóxido Hidrolasas/metabolismo , Neoplasias Hepáticas/genética , Proteínas Virales/metabolismo , Animales , Benzopirenos/toxicidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Aductos de ADN/metabolismo , Epóxido Hidrolasas/genética , Regulación Viral de la Expresión Génica , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Hidrólisis/efectos de los fármacos , Neoplasias Hepáticas/patología , Ratones , Microsomas/efectos de los fármacos , Microsomas/enzimología , Proteínas Virales/genéticaRESUMEN
It's common in edible oil market that adulterating low price oils in high price oils. Sesame oil was often adulterated because of its high quality and price, so the authentication and adulteration of sesame oil were qualitatively and quantitatively analyzed by Fourier transform infrared (FTIR) spectroscopy combined with chemometrics. Firstly, FTIR spectra of sesame oil, soybean oil, and sunflower seed oil in 4,000-650 cm(-1) were analyzed. It was very difficult to detect the difference among the spectra of above edible oils, because they are all mixtures of triglyceride fatty acids and have similar spectra. However, the FTIR data of edible oils in the fingerprint region of 1,800-650 cm(-1) differed slightly because their fatty acid compositions are different, so the data could be classified and recognized by chemometric methods. The authenticity model of sesame oil was built by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). The recognition rate was 100%, and the built model was satisfactory. The classification limits of both soybean oil and sunflower seed oil adulterated in sesame oil were 10%, with the chemometric treatments of standard normal variation (SNV), partial least square (PLS) and PCA. In addition, the FTIR data processed by PCA and PLS were used to establish an analysis model of binary system of sesame oil mixed with soybean oil or sunflower oil, the prediction values had good corresponding relationship with true values, and the relative errors of prediction were between -6.87% and 8.07%, which means the quantitative model was practical. This method is very convenient and rapid after the models have been built, and can be used for rapid detection of authenticity and adulteration of sesame oil. The method is also practical and suitable for the daily analysis of large amount of samples.
Asunto(s)
Contaminación de Alimentos , Aceite de Sésamo/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Ácidos Grasos , Análisis de los Mínimos Cuadrados , Aceites de Plantas , Análisis de Componente Principal , Aceite de Soja , Aceite de Girasol , TriglicéridosRESUMEN
Isolated torsion of a fallopian tube in the third trimester of pregnancy is an uncommon event. Its common symptoms are lower abdominal pain, vomiting, and nausea. Because these symptoms are nonspecific, isolated torsion of a fallopian tube may be misdiagnosed, delaying treatment and the opportunity to preserve the tube. This is a case report of a primipara in her third trimester, whowas misdiagnosed as having acute appendicitis and ovarian cyst torsion. The ultrasound-assisted examination was useful, but the specific diagnosis was made after laparotomy and histopathology. The patient was managed by simultaneous salpingectomy and cesarean section. This surgical intervention prevented adverse obstetric sequelae. We summarize our experience, provide our conclusions, and review 17 relevant studies from the literature to aid clinicians in understanding, diagnosing, and managing this condition in a timely fashion.
RESUMEN
Three-dimensional (3D) hollow carbon is one of advanced nanomaterials widely applied in oxygen reduction reaction (ORR). Herein, iron niobate (FeNb2O6) nanoparticles supported on metal-organic frameworks (MOFs)-derived 3D N-doped interconnected open carbon cages (FeNb2O6/NICC) were prepared by methanol induced assembly and pyrolysis strategy. During the fabrication process, the evaporation of methanol promoted the assembly and cross linkage of ZIF-8, rather than individual particles. The assembled ZIF-8 particles worked as in-situ sacrificial templates, in turn forming hierarchically interconnected open carbon cages after high-temperature pyrolysis. The as-made FeNb2O6/NICC showed a positive onset potential of 1.09 V and a half-wave potential of 0.88 V for the ORR, outperforming commercial Pt/C under the identical conditions. Later on, the as-built Zn-air battery with the FeNb2O6/NICC presented a greater power density of 100.6 mW cm-2 and durable long-cycle stability by operating for 200 h. For preparing 3D hollow carbon materials, this synthesis does not require a tedious removal process of template, which is more convenient than traditional method with silica and polystyrene spheres as templates. This work affords an exceptional example of developing 3D N-doped interconnected hollow carbon composites for energy conversion and storage devices.