RESUMEN
How to characterize short protein sequences to make an effective connection to their functions is an unsolved problem. Here we propose to map the physicochemical properties of each amino acid onto unit spheres so that each protein sequence can be represented quantitatively. We demonstrate the usefulness of this representation by applying it to the prediction of cell penetrating peptides. We show that its combination with traditional composition features yields the best performance across different datasets, among several methods compared. For the convenience of users, a web server has been established for automatic calculations of the proposed features at http://biophy.dzu.edu.cn/SNumD/.
Asunto(s)
Algoritmos , Proteínas/química , Secuencia de Aminoácidos , Análisis de Secuencia de Proteína/métodos , Interfaz Usuario-ComputadorRESUMEN
A Gram-stain-negative, aerobic, non-motile strain, K3CV102501T, was isolated from a soil sample collected from the monsoon evergreen broad-leaved forest of Dinghushan Biosphere Reserve located in Guangdong Province, PR China. The primal colony of strain K3CV102501T was very similar to the fruiting body of myxobacteria on the original isolation plates. Young cultures of strain K3CV102501T contained long (2-4×0.4-0.5 µm) filamentous cells and divided into rod shapes (0.7-1.0×0.6-0.8 µm) after 4 days of incubation at 28 °C. Strain K3CV102501T grew at pH 6.0-9.5 (optimum, pH 6.5-7.5) and 7-42 °C (optimum, 28-35 °C). Phylogenetic analysis based on its 16S rRNA gene sequence showed that strain K3CV102501T belonged to the genus Chitinophagaand showed the highest similarity to C.hitinophaga jiangningensis JCM 19354T (96.9â%). The DNA G+C content of the type strain was 46.6 mol%. The major fatty acids (>10â%) were iso-C15â:â0, C16â:â1ω5c and iso-C17â:â0 3-OH. The major polar lipids were phosphatidylethanolamine and an unidentified aminolipid. Menaquinone-7 was the predominant quinone. The phenotypic, chemotaxonomic and phylogenetic data clearly showed that strain K3CV102501T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga flava sp. nov. is proposed. The type strain is K3CV102501T (=KCTC 62435T=GDMCC 1.1325T).
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Bacteroidetes/clasificación , Bosques , Filogenia , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfatidiletanolaminas/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
BACKGROUND: Intrinsically unstructured or disordered proteins function via interacting with other molecules. Annotation of these binding sites is the first step for mapping functional impact of genetic variants in coding regions of human and other genomes, considering that a significant portion of eukaryotic genomes code for intrinsically disordered regions in proteins. RESULTS: DisBind (available at http://biophy.dzu.edu.cn/DisBind ) is a collection of experimentally supported binding sites in intrinsically disordered proteins and proteins with both structured and disordered regions. There are a total of 226 IDPs with functional site annotations. These IDPs contain 465 structured regions (ORs) and 428 IDRs according to annotation by DisProt. The database contains a total of 4232 binding residues (from UniProt and PDB structures) in which 2836 residues are in ORs and 1396 in IDRs. These binding sites are classified according to their interacting partners including proteins, RNA, DNA, metal ions and others with 2984, 258, 383, 350, and 262 annotated binding sites, respectively. Each entry contains site-specific annotations (structured regions, intrinsically disordered regions, and functional binding regions) that are experimentally supported according to PDB structures or annotations from UniProt. CONCLUSION: The searchable DisBind provides a reliable data resource for functional classification of intrinsically disordered proteins at the residue level.
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Proteínas Intrínsecamente Desordenadas/metabolismo , Interfaz Usuario-Computador , Sitios de Unión , Bases de Datos Factuales , Humanos , Internet , Proteínas Intrínsecamente Desordenadas/química , Estructura Terciaria de ProteínaRESUMEN
About 90% of tuberculosis (TB) patients latently infected with Mycobacterium tuberculosis (Mtb) show no symptoms, yet have a 10% chance in lifetime to progress active TB. Nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. The objective of this work was to detect potential signatures for active TB to further improve the understanding of the biological roles of functional modules involved in this disease. First, targeted networks of active TB and control groups were established via re-weighting protein-protein interaction (PPI) networks using Pearson's correlation coefficient (PCC). Candidate modules were detected from the targeted networks, and the modules with Jaccard score >0.7 were defined as attractors. After that, identification of dys-regulated modules was conducted from the attractors using attract method, Subsequently, gene oncology (GO) enrichment analyses were implemented for genes in the dys-regulated modules. We obtained 33 and 65 candidate modules from the targeted networks of control and active TB groups, respectively. Overall, 13 attractors were identified. Using the cut-off criteria of false discovery rate <0.05, there were 4 dys-regulated modules (Module 1, 2, 3, and 4). Based on the GO annotation results, genes in Modules 1, 2 and 4 were only involved in translation. Most genes in Module 1, 2 and 4 were associated with ribosomes. Accordingly, these dys-regulated modules might serve as potential biomarkers of active TB, facilitating the development for a more efficient, and sensitive diagnostic assay for active TB.
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Algoritmos , Redes Reguladoras de Genes , Mycobacterium tuberculosis/genética , Mapas de Interacción de Proteínas , Tuberculosis/metabolismo , Biomarcadores/análisis , Perfilación de la Expresión Génica/métodos , Regulación Bacteriana de la Expresión Génica , Ontología de Genes , Humanos , Mycobacterium tuberculosis/patogenicidad , Transducción de Señal , Tuberculosis/diagnóstico , Tuberculosis/genéticaRESUMEN
Most natural protein sequences have resulted from millions or even billions of years of evolution. How they differ from random sequences is not fully understood. Previous computational and experimental studies of random proteins generated from noncoding regions yielded inclusive results due to species-dependent codon biases and GC contents. Here, we approach this problem by investigating 10,000 sequences randomized at the amino acid level. Using well-established predictors for protein intrinsic disorder, we found that natural sequences have more long disordered regions than random sequences, even when random and natural sequences have the same overall composition of amino acid residues. We also showed that random sequences are as structured as natural sequences according to contents and length distributions of predicted secondary structure, although the structures from random sequences may be in a molten globular-like state, according to molecular dynamics simulations. The bias of natural sequences toward more intrinsic disorder suggests that natural sequences are created and evolved to avoid protein aggregation and increase functional diversity.
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Proteínas Intrínsecamente Desordenadas/química , Proteínas/química , Aminoácidos/química , Biología Computacional , Bases de Datos de Proteínas , Agregado de Proteínas , Conformación Proteica , Estructura Secundaria de Proteína , Análisis de Secuencia de ProteínaRESUMEN
BACKGROUND: The fermentation performance of a genome-shuffled strain of Candida versatilis S3-5, isolated for improved tolerance to salt, and wild-type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process. RESULTS: The results showed that ethanol produced by the genome shuffled strain S3-5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3-5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3-5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT. CONCLUSIONS: S3-5 exhibited enhanced metabolic ability as compared to the wild-type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3-5 might be an ester-flavour type salt-tolerant yeast. © 2016 Society of Chemical Industry.
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Candida/genética , Candida/metabolismo , Fermentación/genética , Manipulación de Alimentos/métodos , Ingeniería Genética , Tolerancia a la Sal/genética , Candida/crecimiento & desarrollo , Metabolismo de los Hidratos de Carbono , Ácido Cítrico/metabolismo , Etanol/metabolismo , Aromatizantes , Genoma Fúngico/genética , Glucosamina/análogos & derivados , Glucosamina/metabolismo , Malatos/metabolismo , Alimentos de Soja/microbiología , Ácido Succínico/metabolismo , Gusto , Compuestos Orgánicos Volátiles/metabolismoRESUMEN
BACKGROUND: To study the role of miR-143 during embryo implantation in rat. METHODS: MiR-143 expression in rat early pregnancy was detected by Northern blot. The relation between miR-143 and Lifr predicted and confirmed by bioinformatics method, dual-luciferase activity assay, Western blot and immunohistochemistry. The role of miR-143 was detected by MTS, Edu and ranswell chamber assays. RESULTS: The expression level of miR-143 on gestation day 5-8 (g.d. 5-8) was higher than on g.d. 3-4 in uteri of pregnant rat. MiR-143 was mainly localized in the superficial stroma/primary decidual zone, luminal and glandular epithelia. The expression of miR-143 was not significantly influenced by pseudopregnancy, but the activation of delayed implantation and experimentally induced decidualization significantly promoted miR-143 expression. Over-expression of miR-143 in human endometrial stromal cells (ESCs) inhibited cell proliferation, migration and invasion. Knockdown of miR-143 promoted cell proliferation and invasion. The results of recombinant luciferase reporters showed that miR-143 could bind to the 3¢-untranslated region (UTR) of leukemia inhibitory factor receptor (Lifr) to inhibit Lifr translation. CONCLUSIONS: Uterine miR-143 may be involved in the successful pregnancy, especially during the process of blastocyst implantation through regulating Lifr. GENERAL SIGNIFICANCE: This study may have the potential to provide new insights into the understanding of miR-143 function during embryo implantation.
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Implantación del Embrión , MicroARNs/fisiología , Animales , Movimiento Celular , Proliferación Celular , Estradiol/farmacología , Femenino , Humanos , MicroARNs/análisis , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores OSM-LIF/genética , Útero/metabolismoRESUMEN
As one of the major microbes in the soy sauce fermentation, Candida versatilis enriches the flavor and improves the quality of soy sauce. In this study, a combination of five different GC-MS and LC-MS-based metabolome analytical approaches was used to analyze the intracellular, extracellular and whole metabolites of C. versatilis. Our results found out that a total of 132, 244 and 267 different metabolites were detectable from the intracellular, extracellular and whole part, respectively. When exposed to 0. 9 and 18 % salt, respectively, 114, 123 and 129 different intracellular metabolites, 184, 200 and 178 extracellular metabolites and 177, 188 and 186 whole metabolites were detected, respectively. Our data showed that salt enhances the metabolic capacity of C. versatilis, especially its amino acid and enhances the synthesis and secretion of some metabolites of C. versatilis, especially the aldehydes and phenols, such as vanillin, guaiacol and 5-hydroxymethylfurfural. Our data also showed that special attention has to be paid to the generation of biogenic amines when C. versatilis was treated with salt.
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Candida/metabolismo , Metaboloma , Cloruro de Sodio/metabolismo , Estrés Fisiológico , Benzaldehídos/metabolismo , Aminas Biogénicas/biosíntesis , Furaldehído/análogos & derivados , Furaldehído/metabolismo , Guayacol/metabolismo , Análisis de Componente Principal , Tolerancia a la SalRESUMEN
BACKGROUND: This study aimed to enhance and improve the quality and safety of soy sauce. In the present work, the change of biogenic amines, such as histamine, tyramine, cadaverine, spermidine, was examined by the treatment of Candida versatilis and Zygosaccharomyces rouxii, and the influence of salt-tolerant yeast on biogenic amines was analysed during the whole fermentation process. RESULTS: The results showed that the content of biogenic amines was elevated after yeast treatment and the content of biogenic amines was influenced by using yeast. The dominating biogenic amine in soy sauce was tyramine. At the end of fermentation, the concentrations of biogenic amines produced by Zygosaccharomyces rouxii and Candida versatilis in the soy mash were 122.71 mg kg(-1) and 69.96 mg kg(-1) . CONCLUSIONS: The changes of biogenic amines in high-salt liquid soy mash during fermentation process indicated that a variety of biogenic amines were increased in the fermentation ageing period, which may be due to amino acid decarboxylation to form biogenic amines by yeast decarboxylase. The fermentation period of soy sauce should be longer than 5 months because biogenic amines began to decline after this time period.
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Aminas Biogénicas/biosíntesis , Candida/metabolismo , Fermentación , Manipulación de Alimentos/métodos , Alimentos de Soja , Zygosaccharomyces/metabolismo , Aminas Biogénicas/análisis , Cadaverina/análisis , Candida/crecimiento & desarrollo , Histamina/análisis , Concentración de Iones de Hidrógeno , Alimentos de Soja/análisis , Alimentos de Soja/microbiología , Espermidina/análisis , Factores de Tiempo , Tiramina/análisis , Zygosaccharomyces/crecimiento & desarrolloRESUMEN
OBJECTIVE: To investigate the inhibition effect of serum containing n-butanol fractions from Gynostemma pentaphyllum on NG108-15 cell apoptosis induced by Aß25-35 protein in vitro. METHODS: The apoptosis of NG108-15 cells induced by Aß25-35 protein in vitro was evaluated by immunofluorescence and flow cytometry assay. The cellular Caspase-3 level during the apoptosis was determined by ELISA. RESULTS: The serum containing n-butanol fractions from Gynostemma pentaphyllum significantly inhibited the NG108-15 cells apoptosis induced by Aß25-35 protein in vitro,and decreased the cellular Caspase-3 level. CONCLUSION: The inhibition effect of n-butanol fractions from Gynostemma pentaphyllum on NG108-15 cell apoptosis induced by Aß25.35 protein is likely related to its potency on reducing of cellular Caspase-3 level.
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Péptidos beta-Amiloides/farmacología , Apoptosis/efectos de los fármacos , Gynostemma/química , Fragmentos de Péptidos/farmacología , Extractos Vegetales/farmacología , 1-Butanol/química , Caspasa 3 , Línea Celular , Humanos , SueroRESUMEN
OBJECTIVE: To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. CONCLUSION: In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.
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Anemia , Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Trombocitopenia , Humanos , Mesilato de Imatinib/uso terapéutico , Resultado del Tratamiento , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , China , Mesilatos/uso terapéutico , Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/genéticaRESUMEN
OBJECTIVE: To explore the overall survival and prognostic factors of patients over 50 years old with acute myeloid leukemia (AML). METHODS: The clinical data of 222 AML patients aged over 50 years in our hospital from January 2016 and June 2021 were retrospectively analyzed. Kaplan-Meier method was used to evaluate the overall survival (OS) rate, and Cox regression model to evaluate the prognostic factors. RESULTS: The 1-year and 3-year OS rates of all patients were 46.8% and 28.8%, respectively. The recurrence rate of patients who achieved remission during follow-up time was 57%. Both univariate and multivariate analysis showed that advanced age, MLL family fusion gene, PHF6 gene mutation, TP53 gene mutation, intolerance to standard chemotherapy, incomplete remission, complex karyotype, +mar karyotype and inv(3) karyotype were significantly correlated with prognosis (all P <0.05). Negative fusion gene and positive AML- ETO fusion gene had no obvious survival advantage in this population. In patients with complete remission, there was no significant survival advantage in those who achieved minimal residual disease negative. CONCLUSION: AML patients aged over 50 years have a poor outcome and high recurrence rate. The prognosis is affected by multiple factors and has its own characteristics.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Tasa de Supervivencia , Mutación , Femenino , Anciano , Masculino , Inducción de RemisiónRESUMEN
PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
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Antineoplásicos , Arsénico , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Antineoplásicos/efectos adversos , Arsénico/uso terapéutico , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pandemias , Resultado del TratamientoRESUMEN
OBJECTIVE: To detect the changes of Osterix (Osx) mRNA and protein expression in human periodontal ligament cells (HPDLCs) induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and examine the role of BMP-2 and Osx during the osteogenic differentiation of HPDLCs. METHODS: HPDLCs were isolated and cultured in vitro with explant method. Cells at passage 3 were cultured in DMEM with rhBMP-2 at different concentrations (50, 100, 150, 200, 250, 300, 400, and 600 µg/L) for different times (2, 3, 5, 7, 10, 14 and 21 days). Then the expressions of Osx mRNA and protein were measured by real-time reverse transcription (RT)-PCR and Western blotting respectively. Cells were treated with 10 µmol/L SB203580 (p38 inhibitor) to inhibit p38 phosphorylation induced by rhBMP-2. The mineralization nodules formation and the expressions of phosphorylated p38 and Osx mRNA were detected respectively. RESULTS: During the culture of rhBMP-2, the expression of Osx mRNA significantly increased. Initially Osx protein had a low expression and then increased in a time-dependent manner followed by the production of bone-like nodules in HPDLCs. Under the effect of SB203580, the up-regulation of phosphorylated p38 expression induced by rhBMP-2 was significantly inhibited as well as the expression of Osx (Osx mRNA expression: 0.378 ± 0.034 vs 0.134 ± 0.027, Osx protein expression: 0.353 ± 0.024 vs 0.155 ± 0.031, both P < 0.01). Meanwhile the mineralization nodules formed by HPDLCs induced by rhBMP-2 were fewer and delayed. CONCLUSIONS: BMP-2 has a significant positive regulatory role on the expression of Osx in HPDLCs. And p38 pathway is an important link of this regulatory process. Thus, as an important signaling pathway in osteogenic differentiation of HPDLCs, BMP-2/p38/Osx may be involved in periodontal tissue remodeling.
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Proteína Morfogenética Ósea 2/farmacología , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Adolescente , Células Cultivadas , Niño , Humanos , Ligamento Periodontal/citología , Proteínas Recombinantes/farmacología , Factor de Transcripción Sp7RESUMEN
Pro-opiomelancortin (POMC) plays important roles in the regulation of food intake and energy expenditure. The sheep exon 3 of gene POMC was amplified and sequenced by screening the DNA pools to select single nuclear polymorphisms and analyze the association with the growth traits. Two silent SNP mutations (g.273 T/C and g.456 G/A) in Hu sheep were identified. PCR-restriction fragment length polymorphism (RFLP) was used to test the g.273 T/C and the association between the g.273 T/C polymorphism and some growth traits was analyzed in Hu sheep (n = 162) and East Friesian x Hu crossbred sheep (n=130). The results showed that three genotypes, TT, TC and CC, were detected in Hu sheep with the frequencies of 0.469, 0.438 and 0.093, respectively. Two genotypes, TT and TC, were detected in East Friesian x Hu crossbred sheep with the frequencies of 0.754 and 0.246, respectively. The association analysis showed that in Hu sheep the two-month weaning weight, four-month rump height of genotype CC and the four-month body length, cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the four- and six-month weight of genotype CC were significantly higher than those of genotypes TT and TC (P < 0.01); the four-month body height and body length of genotype CC were significantly higher than those of genotypes TT (P < 0.01) and TC (P < 0.05); the four-month cannon circumference of CC genotype was significantly higher than that of TT genotype (P < 0.01). In East Friesian x Hu crossbred sheep the two-month weaning weight, four-month weight, body height, body length, chest depth and cannon circumference of genotype TC were significantly higher than those of genotype TT (P < 0.05); the six-month weight of genotype TC was significantly higher than that of genotype CC (P < 0.01). In conclusion, the exon 3 of gene POMC was associated with growth traits, and C allele was beneficial to the increase of body weight and body size traits of sheep, which potentially afford a good foundation for further study on POMC gene as aided breeding markers for growth traits in sheep.
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Exones , Polimorfismo de Nucleótido Simple , Proopiomelanocortina/genética , Ovinos/crecimiento & desarrollo , Ovinos/genética , Animales , Secuencia de Bases , Tamaño Corporal , Peso Corporal , Femenino , Hibridación Genética , Masculino , Datos de Secuencia Molecular , Carácter Cuantitativo Heredable , Ovinos/metabolismoRESUMEN
OBJECTIVE: To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL). METHODS: CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation. RESULTS: 2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD. CONCLUSION: CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Masculino , Humanos , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Resultado del Tratamiento , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/etiología , Enfermedad Aguda , Enfermedad Injerto contra Huésped/prevención & controlAsunto(s)
Mesilato de Imatinib/administración & dosificación , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico por imagen , MasculinoRESUMEN
OBJECTIVE: The objectives of this study were to measure the anesthesiologists' knowledge and attitudes about OSA and assess the need for additional educational programs focusing on OSA. METHODS: The Obstructive Sleep Apnea Knowledge and Attitude Questionnaire (OSAKA) developed by Helena Metal was translated into Chinese and distributed to anesthesiologists from Shandong Province. Anesthesiologists completed the OSAKA questionnaire containing sections regarding knowledge (18 items) and attitudes about OSA (5 items). RESULTS: A total of 321 questionnaires were completed. The mean total knowledge score was 11.21, with the scores ranging from 2 to 17. The total correct score ratio was 62%. The knowledge score positively corrected with the participants' job titles and attitude scores. None of the dependent variables, such as sex, age, education, and working in a different hospital level, affected the score. CONCLUSION: The study shows that anesthesiologists lack adequate knowledge about OSA. The total correct score ratio was 62%; when they managed an OSA patient, the positive attitude score is mostly below 50%. They have low confidence about OSA patients. It is necessary to develop special training programs on OSA regularly for anesthesiologists after graduation.
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Anestesiología/educación , Educación Médica Continua , Conocimientos, Actitudes y Práctica en Salud , Apnea Obstructiva del Sueño/diagnóstico , Adulto , China , Curriculum , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Cuidados Preoperatorios , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the expression of proteasome ß5 subunit in human atherosclerotic plaque. METHODS: The specimens of carotid endarterectomy were collected from 16 carotid stenosis patients. For the case group, they were divided into 2 groups: plaque (group A) and areas adjacent to plaque (group B). And carotid endarterium was obtained from 6 patients undergoing aortic replacement surgery. Relatively normal arterial intima (subclavian artery & innominate artery) was selected as the control group (group C). Content of proteasome ß5 subunit was evaluated by hematoxylin & eosin (HE) staining, immunohistochemistry and Western blot. RESULTS: (1) In patients with diabetes, hyperlipidemia and probable smoking, proteasome ß5 subunit was enhanced in all groups; (2) Proteasome ß5 subunit was demonstrated in both cytoplasm and nucleus of vascular smooth muscle cells, but mainly confined to cytoplasm; (3)The positive expression rate of ß5 was 9/16 in group A, 11/16 in group B and 6/6 in group C. There was significant divergence in the expression of ß5 in different sample sub-groups: group A (atherosclerotic plaque) < group B (areas adjacent to plaque) < group C (control group). CONCLUSION: The expression of ß5 decrease markedly in human atherosclerotic plaques.
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Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION: CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.