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1.
Artículo en Inglés | MEDLINE | ID: mdl-36459612

RESUMEN

Incomplete multiview clustering (IMC) methods have achieved remarkable progress by exploring the complementary information and consensus representation of incomplete multiview data. However, to our best knowledge, none of the existing methods attempts to handle the uncoupled and incomplete data simultaneously, which affects their generalization ability in real-world scenarios. For uncoupled incomplete data, the unclear and partial cross-view correlation introduces the difficulty to explore the complementary information between views, which results in the unpromising clustering performance for the existing multiview clustering methods. Besides, the presence of hyperparameters limits their applications. To fill these gaps, a novel uncoupled IMC (UIMC) method is proposed in this article. Specifically, UIMC develops a joint framework for feature inferring and recoupling. The high-order correlations of all views are explored by performing a tensor singular value decomposition (t-SVD)-based tensor nuclear norm (TNN) on recoupled and inferred self-representation matrices. Moreover, all hyperparameters of the UIMC method are updated in an exploratory manner. Extensive experiments on six widely used real-world datasets have confirmed the superiority of the proposed method in handling the uncoupled incomplete multiview data compared with the state-of-the-art methods.

2.
Artículo en Inglés | MEDLINE | ID: mdl-35839201

RESUMEN

As a challenging problem, incomplete multi-view clustering (MVC) has drawn much attention in recent years. Most of the existing methods contain the feature recovering step inevitably to obtain the clustering result of incomplete multi-view datasets. The extra target of recovering the missing feature in the original data space or common subspace is difficult for unsupervised clustering tasks and could accumulate mistakes during the optimization. Moreover, the biased error is not taken into consideration in the previous graph-based methods. The biased error represents the unexpected change of incomplete graph structure, such as the increase in the intra-class relation density and the missing local graph structure of boundary instances. It would mislead those graph-based methods and degrade their final performance. In order to overcome these drawbacks, we propose a new graph-based method named Graph Structure Refining for Incomplete MVC (GSRIMC). GSRIMC avoids recovering feature steps and just fully explores the existing subgraphs of each view to produce superior clustering results. To handle the biased error, the biased error separation is the core step of GSRIMC. In detail, GSRIMC first extracts basic information from the precomputed subgraph of each view and then separates refined graph structure from biased error with the help of tensor nuclear norm. Besides, cross-view graph learning is proposed to capture the missing local graph structure and complete the refined graph structure based on the complementary principle. Extensive experiments show that our method achieves better performance than other state-of-the-art baselines.

3.
J Integr Plant Biol ; 64(6): 1145-1156, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35419850

RESUMEN

Current gene delivery methods for maize are limited to specific genotypes and depend on time-consuming and labor-intensive tissue culture techniques. Here, we report a new method to transfect maize that is culture-free and genotype independent. To enhance efficiency of DNA entry and maintain high pollen viability of 32%-55%, transfection was performed at cool temperature using pollen pretreated to open the germination aperture (40%-55%). Magnetic nanoparticles (MNPs) coated with DNA encoding either red fluorescent protein (RFP), ß-glucuronidase gene (GUS), enhanced green fluorescent protein (EGFP) or bialaphos resistance (bar) was delivered into pollen grains, and female florets of maize inbred lines were pollinated. Red fluorescence was detected in 22% transfected pollen grains, and GUS stained 55% embryos at 18 d after pollination. Green fluorescence was detected in both silk filaments and immature kernels. The T1 generation of six inbred lines showed considerable EGFP or GUS transcripts (29%-74%) quantitated by polymerase chain reaction, and 5%-16% of the T1 seedlings showed immunologically active EGFP or GUS protein. Moreover, 1.41% of the bar transfected T1 plants were glufosinate resistant, and heritable bar gene was integrated into the maize genome effectively as verified by DNA hybridization. These results demonstrate that exogenous DNA could be delivered efficiently into elite maize inbred lines recalcitrant to tissue culture-mediated transformation and expressed normally through our genotype-independent pollen transfection system.


Asunto(s)
Nanopartículas de Magnetita , Zea mays , ADN , Genotipo , Plantas Modificadas Genéticamente/genética , Polen/genética , Zea mays/genética
4.
Neural Regen Res ; 17(5): 1096-1105, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34558538

RESUMEN

Long noncoding RNAs (lncRNAs) participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis. Homeobox A11 antisense RNA (HOXA11-AS) is a member of the lncRNA family that has been reported to participate in many inflammatory reactions; however, its role in traumatic brain injury remains unclear. In this study, we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling. The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats, increased brain edema and apoptosis, promoted the secretion of proinflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor α, and promoted the activation of astrocytes and microglia. Microglia were treated with 100 ng/mL lipopolysaccharide for 24 hours to establish in vitro cell models, and then transfected with pcDNA-HOXA11-AS, miR-124-3p mimic, or sh-MDK. The results revealed that HOXA11-AS inhibited miR-124-3p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation. Furthermore, lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes. Forced overexpression of miR-124-3p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes. However, the miR-124-3p-mediated anti-inflammatory effects were reversed by HOXA11-AS. These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the miR-124-3p-MDK axis. This study was approved by the Animal Protection and Use Committee of Southwest Medical University (approval No. SMU-2019-042) on February 4, 2019.

5.
Arch Anim Breed ; 65(4): 417-426, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36756164

RESUMEN

In order to promote the rapid development of the meat sheep industry, a three-way crossbred combination experiment was carried out with Australian White, Dorper, and Charollais sheep as terminal male parents and the elite F1 hybrids of Australian White  × â€¯Small-tailed Han (Han), Dorper  × â€¯Han, and Charollais  × â€¯Han as female parents, which was based on the screening of a two-way crossbred combination in meat sheep. The growth performance of six groups of three-way crossbred combinations and Han lambs was measured and analyzed, and the effect of a polymorphism in the CLPG gene on the growth performance of three-way crossbred lambs was also studied. The results showed that under the same rearing conditions, weight at 3 and 6 months of age and average daily gain from birth to 3 months and from 3 to 6 months of age were all the largest for Australian  × â€¯(Charollais  × â€¯Han) crossbred lambs. They were significantly or extremely significant different from the other three-way crossbred combinations and Han lambs ( P < 0.05 , P < 0.01 ). The body height, body length, chest girth, and cannon bone circumference at 3 months of age and body length, chest girth, and cannon bone circumference at 6 months of age were also the largest for Australian  × â€¯(Charollais  × â€¯Han) crossbred lambs. Among them, body length, chest girth, and cannon bone circumference at 3 months of age were significantly different from the other three-way crossbred combinations and Han lambs ( P < 0.05 ), and body length, chest girth, and cannon bone circumference at 6 months of age were significantly or extremely significant different from the other three-way crossbred combinations and Han lambs ( P < 0.05 , P < 0.01 ). The potential genetic effects of the CLPG gene on the growth performance indicators of three-way crossbred lambs showed that a mutation site ( g .232 C   >   T ) of this gene had two genotypes: CC and CT. Among them, the data of body weights and body sizes from CT genotype individuals at birth, 3 months old, and 6 months old were significantly higher than those of CC genotype individuals, and some indicators showed significant or extremely significant differences ( P < 0.05 , P < 0.01 ), suggesting that higher growth performance was observed in individuals with T alleles. To sum up, the crossbred combination of Australian  × â€¯(Charollais  × â€¯Han) could be suggested as the optimal choice. The T allele of the CLPG gene showed potential advantages in the performance of meat production in meat sheep. Based on the current results, we recommend that the offspring of Australian  × â€¯(Charollais  × â€¯Han) with the T allele should be preferentially utilized for meat sheep production.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 137-144, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33554810

RESUMEN

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
7.
Front Genet ; 11: 616743, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33633772

RESUMEN

Background: Polled intersex syndrome (PIS) leads to reproductive disorders in goats and exerts a heavy influence on goat breeding. Since 2001, the core variant of an 11.7 kb deletion at ~129 Mb on chromosome 1 (CHI1) has been widely used as a genetic diagnostic criterion. In 2020, a ~0.48 Mb insertion within the PIS deletion was identified by sequencing in XX intersex goats. However, the suitability of this variation for the diagnosis of intersex goats worldwide and its further molecular genetic mechanism need to be clarified. Results: The whole-genome selective sweep of intersex goats from China was performed with whole-genome next-generation sequencing technology for large sample populations and a case-control study on interbreeds. A series of candidate genes related to the goat intersexuality phenotype were found. We further confirmed that a ~0.48 Mb duplicated fragment (including ERG and KCNJ15) downstream of the ~20 Mb PIS region was reversely inserted into the PIS locus in intersex Chinese goats and was consistent with that in European Saanen and Valais black-necked goats. High-throughput chromosome conformation capture (Hi-C) technology was then used to compare the 3D structures of the PIS variant neighborhood in CHI1 between intersex and non-intersex goats. A newly found structure was validated as an intrachromosomal rearrangement. This inserted duplication changed the original spatial structure of goat CHI1 and caused the appearance of several specific loop structures in the adjacent ~20 kb downstream region of FOXL2. Conclusions: Results suggested that the novel complex PIS variant genome was sufficient as a broad-spectrum clinical diagnostic marker of XX intersexuality in goats from Europe and China. A series of private dense loop structures caused by segment insertion into the PIS deletion might affect the expression of FOXL2 or other neighboring novel candidate genes. However, these structures require further in-depth molecular biological experimental verification. In general, this study provided new insights for future research on the molecular genetic mechanism underlying female-to-male sex reversal in goats.

8.
3 Biotech ; 9(3): 99, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30800610

RESUMEN

Sex reversal has been studied extensively in vertebrate species, particularly in domestic goats, because polled intersex syndrome (PIS) has seriously affected their production efficiency. In the present study, we used histopathologically diagnosed cases of PIS to identify correlated genomic regions and variants using representative selection signatures and performed GWAS using Restriction-Site Associated Resequencing DNA. We identified 171 single-nucleotide polymorphisms (SNPs) that may have contributed to this phenotype, and 53 SNPs were determined to be located in coding regions using a general linear model. The transcriptome data sets of differentially expressed genes (DEGs) in the pituitary tissues of intersexual and nonintersexual goats were examined using high-throughput technology. A total of 10,063 DEGs and 337 long noncoding RNAs were identified. The DEGs were clustered into 56 GO categories and determined to be significantly enriched in 53 signaling pathways by KEGG analysis. In addition, according to qPCR results, PSPO2 and FSH were significantly more highly expressed in sexually mature pituitary tissues of intersexual goats compared to healthy controls (nonintersexual). These results demonstrate that certain novel potential genomic regions may be responsible for intersexual goats, and the transcriptome data indicate that the regulation of various physiological systems is involved in intersexual goat development. Therefore, these results provide helpful data for understanding the molecular mechanisms of intersex syndrome in goats.

9.
Ecol Evol ; 8(10): 5111-5123, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29876086

RESUMEN

The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D-loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high-frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low-frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.

10.
ACS Appl Mater Interfaces ; 10(20): 17327-17334, 2018 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-29722959

RESUMEN

Raising triplet exciton utilization of pure organic luminescent materials is of significant importance for efficiency advancement of organic light-emitting diodes (OLEDs). Herein, by introducing bromine atom(s) onto a typical molecule (bis(carbazol-9-yl)-4,5-dicyanobenzene) with thermally activated delayed fluorescence, we demonstrate that the heavy atom effect of bromine can increase spin-orbit coupling and promote the reverse intersystem crossing, which endow the molecules with more distinct delayed fluorescence. In consequence, the triplet exciton utilization is improved greatly with the increase of bromine atoms, affording apparently advanced external quantum efficiencies of OLEDs. Utilizing the enhancement effect of bromine atoms on delayed fluorescence should be a simple and promising design concept for efficient organic luminogens with high exciton utilization.

11.
Materials (Basel) ; 10(12)2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29194426

RESUMEN

As one of the most promising technologies for next-generation lighting and displays, white organic light-emitting diodes (WOLEDs) have received enormous worldwide interest due to their outstanding properties, including high efficiency, bright luminance, wide viewing angle, fast switching, lower power consumption, ultralight and ultrathin characteristics, and flexibility. In this invited review, the main parameters which are used to characterize the performance of WOLEDs are introduced. Subsequently, the state-of-the-art strategies to achieve high-performance WOLEDs in recent years are summarized. Specifically, the manipulation of charges and excitons distribution in the four types of WOLEDs (fluorescent WOLEDs, phosphorescent WOLEDs, thermally activated delayed fluorescent WOLEDs, and fluorescent/phosphorescent hybrid WOLEDs) are comprehensively highlighted. Moreover, doping-free WOLEDs are described. Finally, issues and ways to further enhance the performance of WOLEDs are briefly clarified.

12.
Chem Commun (Camb) ; 52(100): 14454-14457, 2016 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-27901534

RESUMEN

Based on a series of new fluorescent emitters, deep blue non-doped multilayer OLEDs with EQEs exceeding 5.10% and single layer devices excluding any charge carrier transporting materials with an EQE of 4.22% were obtained at an extremely high luminance of 10 000 cd m-2.

13.
Discov Med ; 22(119): 7-17, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27585226

RESUMEN

Multidrug resistance (MDR) to Doxorubicin (DOX) remains a major obstacle to successful cancer treatment. The present study sought to overcome the MDR of lung cancer cells and achieve radiosensitization by developing a composite DOX-loaded micelle (M-DOX). M-DOX containing PEG-PCL/Pluronic P105 was prepared by the solvent evaporation method. Lung cancer cell line A549 was adopted in this study. In vitro cytotoxicity, cellular uptake behavior, subcellular distribution, and radiosensitivity were evaluated by the treatment with M-DOX, and free DOX was used as a control. A549 cells treated with M-DOX as opposed to free DOX showed greater cellular uptake as well as greater cytotoxicity. Furthermore, M-DOX reached the mitochondria and lysosome effectively after cellular uptake, and fluorescence used to track M-DOX was found to be surrounding the nucleus. Finally, colony-forming assays demonstrated that M-DOX treatment improved radiosensitization when compared to free DOX. Based on the increased cytotoxicity and radiosensitization, M-DOX could be considered as a promising drug delivery system to overcome MDR in lung cancer therapy.


Asunto(s)
Micelas , Polímeros/farmacología , Células A549 , Antibióticos Antineoplásicos/farmacología , Cromatografía Líquida de Alta Presión , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Citometría de Flujo , Humanos , Neoplasias Pulmonares/metabolismo , Microscopía Electrónica de Transmisión , Polímeros/química , Tolerancia a Radiación/efectos de los fármacos
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(2): 287-91, 2016 Mar.
Artículo en Chino | MEDLINE | ID: mdl-27263312

RESUMEN

OBJECTIVE: To evaluate the efficacy of second-generation tyrosine kinase inhibitor (TKI) in treating chronic myeloid leukemia (CML). METHODS: A total of 97 patients with CML were enrolled. The patients were treated with TKI and monitored with complete blood count, cytogenetic and molecular indicators during the course of therapy. Survival analysis was performed to evaluate its clinical efficacy. RESULTS: The treatment achieved 97.9% complete hematologic response (CHR), 63.9% major cytogenetic response (MCyR), 60.0% complete cytogenetic response (CCyR) and 44.3% major molecular response (MMR) rates. Apart from CHR, better effects were shown in those indicators during chronic phase compared with progressive phase (P < 0.05). The 1-year, 2-year, 3-year and 5-year overall survival (OS) rate was (90.6 ± 3.0)%, (80.1 ± 4.5)%, (77.5 ± 5.0)% and (64.6 ± 9.3)%, respectively, compared with an event-free survival (EFS) rate of (81.1 ± 4.0)%, (64.4 ± 5.3)%, (56.4 ± 6.0)% and (46.2 ± 8.2)%, respectively. The patients had a 1-year, 2-year, 3-year and 5-year progession-free survival (PFS) rate of (87.4 ± 3.4)%, (73.2 ± 4.9)%, (68.9 ± 5.5)% and (57.4 ± 8.7)%, respectively. A difference between chronic phase (better results) and progressive phase (P < 0.05) was also found in survival indicators. The first-line TKI therapy had 100% CHR, 95% MCyR, 95% CCyR and 70% MMR, compared with 97.3% CHR, 56.8% MCyR, 48.6% CCyR and 36.5% MMR for the second-line TKI therapy. Apart from CHR, the first-line therapy produced better results than the seond-line therapy (P < 0.05). CONCLUSION: CML patients in chronic phase and first-line use of TKI have better outcomes.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Inducción de Remisión , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento
15.
Adv Mater ; 28(23): 4614-9, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27062637

RESUMEN

A chromaticity-adjustable yellow thermally activated delayed fluorescence (TADF) material, PXZDSO2 as a triplet harvester provides a rational device concept, giving two-color and three-color pure organic white organic light-emitting diodes (WOLEDs) with unprecedented color-rendering index of 95 and external quantum efficiency of 19.2%.

16.
Nanotechnology ; 27(12): 124001, 2016 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-26891478

RESUMEN

Two blue fluorescent emitters were utilized to construct simplified organic light-emitting diodes (OLEDs) and the remarkable difference in device performance was carefully illustrated. A maximum current efficiency of 4.84 cd A(-1) (corresponding to a quantum efficiency of 4.29%) with a Commission Internationale de l'Eclairage (CIE) coordinate of (0.144, 0.127) was achieved by using N,N-diphenyl-4″-(1-phenyl-1H-benzo[d]imidazol-2-yl)-[1, 1':4', 1″-terphenyl]-4-amine (BBPI) as a non-doped emission layer of the simplified blue OLEDs without carrier-transport layers. In addition, simplified fluorescent/phosphorescent (F/P) hybrid warm white OLEDs without carrier-transport layers were fabricated by utilizing BBPI as (1) the blue emitter and (2) the host of a complementary yellow phosphorescent emitter (PO-01). A maximum current efficiency of 36.8 cd A(-1) and a maximum power efficiency of 38.6 lm W(-1) were achieved as a result of efficient energy transfer from the host to the guest and good triplet exciton confinement on the phosphorescent molecules. The blue and white OLEDs are among the most efficient simplified fluorescent blue and F/P hybrid white devices, and their performance is even comparable to that of most previously reported complicated multi-layer devices with carrier-transport layers.

17.
ACS Appl Mater Interfaces ; 7(15): 7869-77, 2015 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-25826288

RESUMEN

Two blue fluorophores with excellent hybridized local and charge-transfer (HLCT) and "hot exciton" properties were developed as the blue emitter and the host for orange-red phosphor to achieve highly efficient fluorescent/phosphorescent (F/P) hybrid white organic light-emitting diodes (WOLEDs) in a single-emissive-layer single-dopant (SEML-SD) architecture even at a high concentration of phosphorescent dopant. In the devices, part of the triplet excitons of the blue fluorophores can be utilized to realize reverse intersystem crossing from the triplet excited states to the singlet excited states for blue emission, and the diffusion volume range of the triplet excitons is reduced significantly. When the phosphorescent dopant concentration is up to 1.0 wt %, which is ten times higher than the traditional single-EML-SD F/P hybrid WOLEDs, highly efficient white emission was still achieved with maximum total external quantum efficiency (EQE) of 23.8%, current efficiency (CE) of 56.1 cd A(-1), and power efficiency (PE) of 62.9 lm W(1-). The results will supply a novel method for obtaining high efficiency F/P hybrid WOLEDs in a SEML-SD architecture with easily controllable doping concentration.

18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(4): 647-51, 2014 Jul.
Artículo en Chino | MEDLINE | ID: mdl-25286693

RESUMEN

OBJECTIVE: To evaluate the effects of tyrosine kinase inhibitors (TKI) in the treatment of chronic myeloid leukemia. METHODS: There were total 655 cases of chronic myeloid leukemia treated in one single-institution enrolled in this study. The dosage of TKI Imatinib was 400 mg/d for chronic phase, 600 mg/d for accelerated and blast phase respectively. Complete blood count, cytogenetic and molecular studies were regularly monitored during the course of therapy. The therapeutic effect was evaluated and the survival analysis was performed. RESULTS: The total complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and major molecular response (MMR) rates were 92.1%, 75.8%, 73.1% and 47.9% respectively. 1-year, 3-year, 5-year and 10-year overall survival (OS) rates were (96.3 +/- 0.8)%, (86.3 +/-1.8)%, (79.0 +/- 2.4)% and (66.5 +/- 4.8)% respectively. 1 year, 3-year, 5-year and 10-year event-free survival (EFS) rates were (92.2 +/- 1.1)%, (77.9 +/- 2.1)%, (67.9 +/- 6.8)% and (35.8 +/- 6.0)% respectively. The proportion of the patients in chronic phase achieving CHR, MCyR, CCyR and MMR were 98.7%, 82.5%, 79.4% and 52.4% respectivly. Compared with chronic phase patients, the efficacy of IM in the treatment of accelerated phase and blast phase patients was significantly lower. The effect of TKI in early chronic phase was better than that in late chronic phase. Early molecular response was associated with a better 5-year EFS, but not OS. CONCLUSION: CML patients in chronic phase treated with TKI have a better outcome. The earlier TKI be used, the better the prognosis and efficacy be achieved.


Asunto(s)
Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Humanos , Mesilato de Imatinib , Pronóstico , Proteínas Tirosina Quinasas , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento
19.
Int J Mol Sci ; 14(1): 850-70, 2013 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-23344045

RESUMEN

The novel compound JRS-15 was obtained through the chemical modification of xylocydine. JRS-15 exhibited much stronger cytotoxic and pro-apoptotic activity than its parent compound in various cancer cell lines, with IC(50) values in HeLa, HepG2, SK-HEP-1, PC-3M and A549 cells ranging from 12.42 to 28.25 µM. In addition, it is more potent for killing cancer than non-cancerous cells. Mechanistic studies showed that JRS-15 treatment arrested cell cycle at the G1/S phase, which further triggered the translocation of Bax and Bak to the mitochondria, resulting in mitochondrial membrane potential (MMP) depolarization and the subsequent release of cytochrome c and the second mitochondria-derived activator of caspase (Smac). The sequential activation of caspase-9 and caspase-3/7 and the cleavage of poly (ADP-ribose) polymerase (PARP) were observed following these mitochondrial events. Caspase-8, an initiator caspase that is required to activate the membrane receptor-mediated extrinsic apoptosis pathway was not activated in JRS-15-treated cells. Further analysis showed that the levels of the anti-apoptotic proteins Bcl-xL and XIAP were significantly reduced upon JRS-15 treatment. Furthermore, the caspase-9 inhibitor z-LEHD-fmk, the pan-caspase inhibitor z-VAD-fmk, and Bcl-xL or XIAP overexpression all effectively prevented JRS-15-induced apoptosis. Taken together, these results indicate that JRS-15 induces cancer cell apoptosis by regulating multiple apoptosis-related proteins, and this compound may therefore be a good candidate reagent for anticancer therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Mitocondrias/efectos de los fármacos , Nucleósidos/farmacología , Transducción de Señal/efectos de los fármacos , Caspasas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Células HeLa , Células Hep G2 , Humanos , Immunoblotting , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/fisiología , Estructura Molecular , Neoplasias/metabolismo , Neoplasias/patología , Nucleósidos/química , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Proteína bcl-X/metabolismo
20.
Yi Chuan ; 34(1): 102-12, 2012 Jan.
Artículo en Chino | MEDLINE | ID: mdl-22306879

RESUMEN

Magnaporthe oryzae is speculated to express and translocate a set of effector proteins to interfere with rice innate immunity and to promote its invasion. In this study, we carried out a transcriptome analysis of early interaction between rice and M. oryzae using a next generation sequencing technology to identify putative effector protein genes. We totally obtained 338 942 M. oryzae derived sequence tags from around 12.5 M gross mixed tags by referring the genome sequence of reference strain 70-15. These M. oryzae sequences were finally mapped to 779 predicted genes. Of these 799 genes, 108 were predicted to be involved in the interaction between rice and M. oryzae and 42 encoded proteins predicted to be secreted. Expression of these 42 putative secreted protein genes were further assessed using a reverse transcription polymerase chain reaction (RT-PCR) method, which revealed that 12 of them were expressed during the infection. Four of these 12 expressed genes were further confirmed to be expressed specifically during the infection. This study demonstrated an attempt to isolate M. oryzae genes, especially those putative effector protein genes, which are expressed specifically at the early interaction stage using a next-generation sequencing technology.


Asunto(s)
Proteínas Fúngicas/genética , Perfilación de la Expresión Génica , Interacciones Huésped-Patógeno , Magnaporthe/genética , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Análisis de Secuencia de ADN/métodos , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Magnaporthe/metabolismo
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