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1.
Nano Lett ; 23(5): 2056-2064, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36695738

RESUMO

The phenotype of tumor-associated macrophages plays an important role in their function of regulating the tumor immune microenvironment. The M1-phenotype macrophages display tumor-killing and immune activating functions. Here we show that the tobacco mosaic virus (TMV), a rod-like plant virus, can polarize macrophages to an M1 phenotype and shape a tumor-suppressive microenvironment. RAW 264.7 cells and bone marrow derived-macrophages (BMDMs) can recognize TMV via Toll-like receptor-4, and then the MAPK and NF-κB signaling pathways are activated, leading to the production of pro-inflammatory factors. Furthermore, the in vivo assessments on a subcutaneous co-injection tumor model show that the TMV-polarized BMDMs shape a tumor-suppressive microenvironment, resulting in remarkable delay of 4T1 tumor growth. Another in vivo assessment on an established tumor model indicates the high tumor-metastasis-inhibiting capacity of TMV-polarized BMDMs. This work suggests a role for this plant virus in macrophage-mediated therapeutic approaches and provides a strategy for tumor immunotherapy.


Assuntos
Vírus do Mosaico do Tabaco , Animais , Camundongos , Macrófagos , Imunoterapia , Células RAW 264.7 , Microambiente Tumoral
2.
EMBO J ; 34(13): 1829-43, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-25921062

RESUMO

During nuclear DNA replication, proofreading-deficient DNA polymerase α (Pol α) initiates Okazaki fragment synthesis with lower fidelity than bulk replication by proofreading-proficient Pol δ or Pol ε. Here, we provide evidence that the exonuclease activity of mammalian flap endonuclease (FEN1) excises Pol α replication errors in a MutSα-dependent, MutLα-independent mismatch repair process we call Pol α-segment error editing (AEE). We show that MSH2 interacts with FEN1 and facilitates its nuclease activity to remove mismatches near the 5' ends of DNA substrates. Mouse cells and mice encoding FEN1 mutations display AEE deficiency, a strong mutator phenotype, enhanced cellular transformation, and increased cancer susceptibility. The results identify a novel role for FEN1 in a specialized mismatch repair pathway and a new cancer etiological mechanism.


Assuntos
Reparo de Erro de Pareamento de DNA , DNA Polimerase I/metabolismo , DNA/metabolismo , Endonucleases Flap/metabolismo , Proteína MutS de Ligação de DNA com Erro de Pareamento/metabolismo , Animais , Células Cultivadas , Reparo de Erro de Pareamento de DNA/genética , Replicação do DNA/genética , Embrião de Mamíferos , Feminino , Endonucleases Flap/classificação , Endonucleases Flap/genética , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Proteína MutS de Ligação de DNA com Erro de Pareamento/genética , Saccharomyces cerevisiae
3.
Exp Cell Res ; 362(2): 279-286, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29174981

RESUMO

Tumor cells often encounter hypoglycemic microenvironment due to rapid cell expansion. It remains elusive how tumors reprogram the genome to survive the metabolic stress. The tumor suppressor TIP60 functions as the catalytic subunit of the human NuA4 histone acetyltransferase (HAT) multi-subunit complex and is involved in many different cellular processes including DNA damage response, cell growth and apoptosis. Attenuation of TIP60 expression has been detected in various tumor types. The function of TIP60 in tumor development has not been fully understood. Here we found that suppressing TIP60 inhibited p53 K120 acetylation and thus rescued apoptosis induced by glucose deprivation in hepatocellular cancer cells. Excitingly, Lys-104 (K104), a previously identified lysine acetylation site of TIP60 with unknown function, was observed to be indispensable for inducing p53-mediated apoptosis under low glucose condition. Mutation of Lys-104 to Arg (K104R) impeded the binding of TIP60 to human NuA4 complex, suppressed the acetyltransferase activity of TIP60, and inhibited the expression of pro-apoptotic genes including NOXA and PUMA upon glucose starvation. These findings demonstrate the critical regulation of TIP60/p53 pathway in apoptosis upon metabolic stress and provide a novel insight into the down-regulation of TIP60 in tumor cells.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Lisina Acetiltransferase 5/genética , Proteína Supressora de Tumor p53/genética , Acetilação , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Dano ao DNA/genética , Regulação Neoplásica da Expressão Gênica , Histona Acetiltransferases/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Estresse Fisiológico/genética
4.
Sensors (Basel) ; 16(7)2016 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-27447631

RESUMO

Existing automatic building extraction methods are not effective in extracting buildings which are small in size and have transparent roofs. The application of large area threshold prohibits detection of small buildings and the use of ground points in generating the building mask prevents detection of transparent buildings. In addition, the existing methods use numerous parameters to extract buildings in complex environments, e.g., hilly area and high vegetation. However, the empirical tuning of large number of parameters reduces the robustness of building extraction methods. This paper proposes a novel Gradient-based Building Extraction (GBE) method to address these limitations. The proposed method transforms the Light Detection And Ranging (LiDAR) height information into intensity image without interpolation of point heights and then analyses the gradient information in the image. Generally, building roof planes have a constant height change along the slope of a roof plane whereas trees have a random height change. With such an analysis, buildings of a greater range of sizes with a transparent or opaque roof can be extracted. In addition, a local colour matching approach is introduced as a post-processing stage to eliminate trees. This stage of our proposed method does not require any manual setting and all parameters are set automatically from the data. The other post processing stages including variance, point density and shadow elimination are also applied to verify the extracted buildings, where comparatively fewer empirically set parameters are used. The performance of the proposed GBE method is evaluated on two benchmark data sets by using the object and pixel based metrics (completeness, correctness and quality). Our experimental results show the effectiveness of the proposed method in eliminating trees, extracting buildings of all sizes, and extracting buildings with and without transparent roof. When compared with current state-of-the-art building extraction methods, the proposed method outperforms the existing methods in various evaluation metrics.

5.
J Nanosci Nanotechnol ; 14(5): 3735-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24734624

RESUMO

Ln3+ (Ln3+ = Ce3+, Tb3+) single doped and/or co-doped NaGdF4 phosphors have been synthesized through a solid state reaction method under a weak reducing N2/H2 (95/5) atmosphere. The phosphors were characterized by X-ray diffraction (XRD) patterns, room temperature photoluminescence (PL) excitation and emission spectra, and luminescent dynamics decay curves. XRD analysis indicated that the phosphors were in the hexagonal phase and crystallized well. Under Ce3+ 4f-5d 252 nm excitation, the Ce3+ single doped phosphor emitted near ultraviolet light peaking at 398 nm. Under host Gd3+ 275 nm sensitization and direct Tb3+ 4f-4f 380 nm excitation, the Tb3+ single doped NaGdF4 phosphor gave blue and/or green light. Under sensitizer Ce3+ 4f-5d 252 nm and host Gd3+ 4f-4f 275 nm sensitization and direct Tb3+ 4f-4f 380 nm excitation, the Ce3+/Tb3+ co-doped NaGdF4 phosphors had blue and/or green light. With fixed Ce3+ concentrations in the Ce3+/Tb3+ co-doped phosphors, the blue light of Tb3+ became weaker and the green light of Tb3+ became stronger with the increase of Tb3+ concentrations, which was caused by the cross relaxation process 5D3 --> 5D4:7F6 --> F0. The experimental results suggested that the Ce3+/Tb3+ co-doped and Tb3+ single doped NaGdF4 phosphors might be used as blue and/or green light emitting materials.

6.
Updates Surg ; 76(3): 1009-1014, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38175503

RESUMO

BACKGROUND: Sacrococcygeal sinus ulcers are caused by pressure sores, trauma, or surgery. Several surgical techniques have been developed for its treatment; however, studies are ongoing to develop the ideal method. The present study aims to introduce an innovative application of gluteus maximus muscle flaps (GMMFs) packing combined with local random pattern skin flaps (RPSFs) in repairing sacrococcygeal sinus tracts (SSTs). METHODS: This was a prospective analysis study conducted on the patients (n = 26) with SSTs underwent an innovative repairing surgery in Qilu Hospital of Shandong University, China between December 2015 and December 2020. The repairing surgery was GMMFs combined with RPSFs. The demographic information and the clinical parameters including operative time, postoperative healing time, and recurrence rate were used to evaluate the efficacy of the operation. RESULTS: Except one case of partial necrosis at the edge of the flap due to severe fibrosis, which was cured after dressing change, all the other cases showed effective healing after the operation. CONCLUSION: The combined application of GMMFs and RPSFs for the treatment of sacrococcygeal sinus tracts gains the advantages of short operative time, quick postoperative recovery, and low postoperative recurrence rate.


Assuntos
Região Sacrococcígea , Retalhos Cirúrgicos , Humanos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Cicatrização , Resultado do Tratamento , Procedimentos de Cirurgia Plástica/métodos , Úlcera por Pressão/cirurgia , Duração da Cirurgia , Idoso , Músculo Esquelético/cirurgia , Nádegas/cirurgia
7.
Adv Healthc Mater ; : e2303755, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424475

RESUMO

Short-chain antifungal peptides (AFPs) inspired by histatin 5 have been designed to address the problem of antifungal drug resistance. These AFPs demonstrate remarkable antifungal activity, with a minimal inhibitory concentration as low as 2 µg mL-1 . Notably, these AFPs display a strong preference for targeting fungi rather than bacteria and mammalian cells. This is achieved by binding the histidine-rich domains of the AFPs to the Ssa1/2 proteins in the fungal cell wall, as well as the reduced membrane-disrupting activity due to their low amphiphilicity. These peptides disrupt the nucleus and mitochondria once inside the cells, leading to reactive oxygen species production and cell damage. In a mouse model of vulvovaginal candidiasis, the AFPs demonstrate not only antifungal activity, but also promote the growth of beneficial Lactobacillus spp. This research provides valuable insights for the development of fungus-specific AFPs and offers a promising strategy for the treatment of fungal infectious diseases.

8.
Genome Res ; 20(9): 1238-49, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20627892

RESUMO

The functional complexity of the rice transcriptome is not yet fully elucidated, despite many studies having reported the use of DNA microarrays. Next-generation DNA sequencing technologies provide a powerful approach for mapping and quantifying the transcriptome, termed RNA sequencing (RNA-seq). In this study, we applied RNA-seq to globally sample transcripts of the cultivated rice Oryza sativa indica and japonica subspecies for resolving the whole-genome transcription profiles. We identified 15,708 novel transcriptional active regions (nTARs), of which 51.7% have no homolog to public protein data and >63% are putative single-exon transcripts, which are highly different from protein-coding genes (<20%). We found that approximately 48% of rice genes show alternative splicing patterns, a percentage considerably higher than previous estimations. On the basis of the available rice gene models, 83.1% (46,472 genes) of the current rice gene models were validated by RNA-seq, and 6228 genes were identified to be extended at the 5' and/or 3' ends by at least 50 bp. Comparative transcriptome analysis demonstrated that 3464 genes exhibited differential expression patterns. The ratio of SNPs with nonsynonymous/synonymous mutations was nearly 1:1.06. In total, we interrogated and compared transcriptomes of the two rice subspecies to reveal the overall transcriptional landscape at maximal resolution.


Assuntos
Perfilação da Expressão Gênica , Oryza/genética , Análise de Sequência de RNA , Processamento Alternativo , Sequência de Bases , Genes de Plantas , Genoma de Planta , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único
9.
Adv Healthc Mater ; 12(10): e2202409, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36588425

RESUMO

Fungal hyphae deeply invade the cornea in fungal keratitis. The corneal stroma hinders the infiltration of antifungal drugs and reduces their bioavailability. Here, this work reports a peptide conjugate nano-assembly that permeates the stroma and kills the pathogen without irritating the ocular cornea. The hydrophilic surface of the nano-assembly ensures deep permeation into the stroma. When encountering a fungal hyphal cell, the nano-assembly disassembles and exposes the α-helical peptide to destroy the fungal membrane, thus inactivating the pathogen. In a rabbit model of fungal keratitis, the nano-assembly exhibits a better therapeutic effect than commercially available natamycin ophthalmic suspension. Peptide conjugates with a nano-assembled structure and assembly-disassembly behavior could serve as the foundation of a new therapy for fungal keratitis.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Animais , Coelhos , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Córnea , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Antifúngicos/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico
10.
J Colloid Interface Sci ; 641: 126-134, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36931211

RESUMO

Surface-associated microbe contamination by Gram-negative bacteria poses a serious problem in medical care. Cationic peptides or polymers are the main materials used for antibacterial surface coating, but the positive charge may lead to blood coagulation. Therefore, exploiting surface coating which is free of positive charge and is effective for Gram-negative bacteria inactivation is in urgent need. In this study, inspired by the affinity between lipopolysaccharides of Gram-negative bacteria and Toll-like receptors of immune cells, we develop a leucine-based tetrapeptide coating strategy for combating Gram-negative bacteria. The obtained surface has excellent bactericidal activity against Gram-negative bacteria like Pseudomonas aeruginosa and Escherichia coli. A 1 mm2 coated glass surface could kill > 9.9 × 104 CFU bacteria in 1 h and has nearly no damage to mammal cells. Moreover, this surface coating strategy could be applied on various surfaces like glass slices, glass capillary cavity and thermoplastic polyurethane slices. And the coated surface could largely mitigate the microbe contamination in an in vivo subcutaneous implantation. This work paves a new way for antibacterial surface-coating which is behaving no positive charge and is of great importance for biomedical devices.


Assuntos
Antibacterianos , Peptídeos , Animais , Leucina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas , Bactérias , Materiais Revestidos Biocompatíveis/química , Mamíferos
11.
BMC Genomics ; 13: 721, 2012 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-23259405

RESUMO

BACKGROUND: Cis-natural antisense transcripts (cis-NATs) are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs), which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. RESULTS: We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq) to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa). Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set), 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. CONCLUSIONS: Our study profiles an abundance of cis-NATs and nat-siRNAs in rice. These data are valuable for gaining insight into the complex function of the rice transcriptome.


Assuntos
Oryza/genética , RNA Interferente Pequeno/genética , Transcriptoma/genética , Sequência de Bases , Northern Blotting , Primers do DNA/genética , Perfilação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microdissecção e Captura a Laser , Dados de Sequência Molecular , Oryza/metabolismo , Folhas de Planta/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Front Genet ; 13: 905581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754829

RESUMO

Background: Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of PSMD2 in lung adenocarcinoma. Methods: The Cancer Genome Atlas (TCGA) was conducted to analyze PSMD2 expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of PSMD2 on survival. cBioPortal database was conducted to identify the mutation characteristics of PSMD2. Functional enrichment was performed to determine PSMD2-related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of PSMD2 at single-cell resolution. PSMD2-related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between PSMD2 expression and tumor-infiltrating lymphocytes (TILs). Results: Both mRNA and protein expression of PSMD2 were significantly elevated in lung adenocarcinoma. High expression of PSMD2 was significantly correlated with high T stage (p = 0.014), lymph node metastases (p < 0.001), and TNM stage p = 0.005). Kaplan-Meier curves indicated that high expression of PSMD2 was correlated with poor overall survival (38.2 vs. 59.7 months, p < 0.001) and disease-specific survival (59.9 months vs. not available, p = 0.004). Multivariate analysis suggested that PSMD2 was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024-2.114, p = 0.037). PSMD2 had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of PSMD2 was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested PSMD2 expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated PSMD2 expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that PSMD2 expression was correlated with immune cell infiltration levels and abundance of TILs. Conclusion: The upregulation of PSMD2 is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that PSMD2 is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.

13.
IEEE Trans Image Process ; 31: 721-733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34928799

RESUMO

Bidirectional mapping-based generalized zero-shot learning (GZSL) methods rely on the quality of synthesized features to recognize seen and unseen data. Therefore, learning a joint distribution of seen-unseen classes and preserving the distinction between seen-unseen classes is crucial for GZSL methods. However, existing methods only learn the underlying distribution of seen data, although unseen class semantics are available in the GZSL problem setting. Most methods neglect retaining seen-unseen classes distinction and use the learned distribution to recognize seen and unseen data. Consequently, they do not perform well. In this work, we utilize the available unseen class semantics alongside seen class semantics and learn joint distribution through a strong visual-semantic coupling. We propose a bidirectional mapping coupled generative adversarial network (BMCoGAN) by extending the concept of the coupled generative adversarial network into a bidirectional mapping model. We further integrate a Wasserstein generative adversarial optimization to supervise the joint distribution learning. We design a loss optimization for retaining distinctive information of seen-unseen classes in the synthesized features and reducing bias towards seen classes, which pushes synthesized seen features towards real seen features and pulls synthesized unseen features away from real seen features. We evaluate BMCoGAN on benchmark datasets and demonstrate its superior performance against contemporary methods.

14.
Front Genet ; 13: 989460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159971

RESUMO

Background: Deoxythymidylate kinase (DTYMK) has been reported to correlate with the progression of hepatocellular carcinoma. However, the role of DTYMK in human cancers is not studied. In this study, we studied the prognostic value, functional states, and correlations with immune infiltration of DTYMK in human cancers. Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), the search tool for the retrieval of interacting genes (STRING), GeneMANIA, cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource (TIMER) databases were utilized to analyze DTYMK in cancers. Results: In general, DTYMK is abnormally expressed between most human cancer and normal tissues from a pan-cancer perspective. DTYMK can be used as a diagnostic biomarker to differentiate tumor tissues from normal tissues in most tumors. Upregulation of DTYMK predicted poor survival status in most cancer types in TCGA. Moreover, DTYMK expression was correlated with the T stage in ACC, BRCA, KIRC, LIHC, and LUAD, with the N stage in BLCA, HNSC, KICH, KIRC, LUAD, LUSC, and THCA, with the M stage in ACC, KIRC, KIRP, and LUAD, with TNM stage in ACC, KIRC, LIHC, LUAD, and LUSC. In addition, based on single-cell sequencing data, we concluded that the expression of DTYMK was correlated with the functional status of the cell cycle, DNA damage, DNA repair, invasion, EMT, and proliferation. Finally, DTYMK expression was correlated with six infiltrating immune cells, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells by investigating TIMER. Conclusion: Our findings suggested that abnormally expressed DTYMK was correlated with poor survival, malignant functional status, and immune infiltrates. DTYMK might be served as a potential biomarker for diagnosis and poor prognosis in various cancer types. DTYMK might act as a potential target for immune therapy.

15.
Front Genet ; 12: 671585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149814

RESUMO

BACKGROUND: Protein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma. METHODS: Transcriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the "ClusterProfiler" package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). RESULTS: The expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates. CONCLUSION: Upregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.

16.
Front Genet ; 12: 721021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925439

RESUMO

Background: aldolase A (ALDOA) has been reported to be involved in kinds of cancers. However, the role of ALDOA in lung adenocarcinoma has not been fully elucidated. In this study, we explored the prognostic value and correlation with immune infiltration of ALDOA in lung adenocarcinoma. Methods: The expression of ALDOA was analyzed with the Oncomine database, the Cancer Genome Atlas (TCGA), and the Human Protein Atlas (HPA). Mann-Whitney U test was performed to examine the relationship between clinicopathological characteristics and ALDOA expression. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were conducted to describe the diagnostic and prognostic importance of ALDOA. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct PPI networks and identify hub genes. Functional annotations and immune infiltration were conducted. Results: The mRNA and protein expression of ALDOA were higher in lung adenocarcinoma than those in normal tissues. The overexpression of ALDOA was significantly correlated with the high T stage, N stage, M stage, and TNM stage. Kaplan-Meier showed that high expression of ALDOA was correlated with short overall survival (38.9 vs 72.5 months, p < 0.001). Multivariate analysis revealed that ALDOA (HR 1.435, 95%CI, 1.013-2.032, p = 0.042) was an independent poor prognostic factor for overall survival. Functional enrichment analysis showed that positively co-expressed genes of ALDOA were involved in the biological progress of mitochondrial translation, mitochondrial translational elongation, and negative regulation of cell cycle progression. KEGG pathway analysis showed enrichment function in carbon metabolism, the HIF-1 signaling pathway, and glycolysis/gluconeogenesis. The "SCNA" module analysis indicated that the copy number alterations of ALDOA were correlated with three immune cell infiltration levels, including B cells, CD8+ T cells, and CD4+ T cells. The "Gene" module analysis indicated that ALDOA gene expression was negatively correlated with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Conclusion: Our study suggested that upregulated ALDOA was significantly correlated with tumor progression, poor survival, and immune infiltrations in lung adenocarcinoma. These results suggest that ALDOA is a potential prognostic biomarker and therapeutic target in lung adenocarcinoma.

17.
World J Clin Cases ; 9(24): 7043-7052, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540959

RESUMO

BACKGROUND: Patients' knowledge about the characteristics of their own cancer could be an important factor for understanding treatment regimens and adhering to therapies. However, to date nothing is known about the awareness among Chinese breast cancer patients about the characteristics of their own tumors. AIM: To investigate how much knowledge that Chinese breast cancer patients have about their tumor characteristics and the impact of health and education literacy on the acquisition of such information. METHODS: The survey was administered to patients who were diagnosed with breast cancer from 2017 to 2019 in three hospitals in China, and who came in for regular follow-up on an outpatient basis. We collected responses from 226 respondents who were asked about their cancer characteristics (stage, grade, and estrogen receptor status and human epidermal growth factor receptor 2 status of the cancer), and evaluated the correctness by comparing with their medical records. Logistic regression was used to assess the probability of knowing and of correctly answering questions. We also analyzed the association between our findings and the level of the patient's education and their health literacy. RESULTS: Overall, 20.80% to 57.96% of the patients reported knowing about the characteristics of breast cancer; of these, 10.18% to 46.46% reported these characteristics correctly. Education, age, and health literacy were all significantly associated with awareness rate, and with the level to which this information was accurate. CONCLUSION: Breast cancer patients in China know little about their disease, and better education aimed at improving their knowledge about cancer characteristics is urgently needed. The low level of awareness could represent a deficiency of communication between surgeons and patients, which may be one of the reasons why medical disputes occur in China.

18.
Onco Targets Ther ; 13: 10775-10783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122916

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value. MATERIALS AND METHODS: The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan-Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model. RESULTS: CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls (P < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage (P = 0.039) and distant metastasis (P = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels (P = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS. CONCLUSION: Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma.

19.
Biochem Biophys Res Commun ; 379(4): 985-9, 2009 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-19135985

RESUMO

The plant-specific NAC (NAM, ATAF1/2, CUC2) transcription factors play diverse roles in plant development and stress responses. In this study, a rice NAC gene, ONAC045, was functionally characterized, especially with regard to its role in abiotic stress resistance. Expression analysis revealed that ONAC045 was induced by drought, high salt, and low temperature stresses, and abscisic acid (ABA) treatment in leaves and roots. Transcriptional activation assay in yeast indicated that ONAC045 functioned as a transcriptional activator. Transient expression of GFP-ONAC045 in onion epidermal cells revealed that ONAC045 protein was localized in the nucleus. Transgenic rice plants overexpressing ONAC045 showed enhanced tolerance to drought and salt treatments. Two stress-responsive genes were upregulated in transgenic rice. Together, these results suggest that ONAC045 encodes a novel stress-responsive NAC transcription factor and is potential useful for engineering drought and salt tolerant rice.


Assuntos
Secas , Oryza/fisiologia , Tolerância ao Sal , Fatores de Transcrição/biossíntese , Sequência de Aminoácidos , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Oryza/genética , Tolerância ao Sal/genética , Fatores de Transcrição/genética , Ativação Transcricional
20.
Oncol Rep ; 42(1): 361-369, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059082

RESUMO

Lung cancer nanotherapeutics aim to overcome the limitations of conventional therapeutic methods. In the present study, a self­assembled amphiphilic prodrug­based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. D­alpha­tocopheryl polyethylene glycol 1000 succinate (TPGS) conjugated to doxorubicin (DOX) through disulfide (S­S) bonds to constitute TPGS­S­S­DOX was synthesized; furthermore, hyaluronic acid (HA) was conjugated to TPGS to obtain HA­TPGS. TPGS­S­S­DOX prodrug­based and HA­TPGS ligand­modified nanoparticles (HA­TPGS DOX­NPs) were prepared for the treatment of lung cancer. In vitro and in vivo evaluation of the system was performed on lung cancer cell lines and lung tumor­bearing mice. HA­TPGS DOX­NPs had a uniformly spherical shape with a white core and grey shell, with a size of 172.3 nm and a polydispersity index of 0.16. All of the NPs exhibited a drug encapsulation efficiency of >90%. The blank NPs exhibited low toxicity to all the tested cell lines, resulting in viabilities of >85%. HA­TPGS DOX­NPs had a more prominent in vitro antitumor effect than the other NPs tested, with cell viabilities of 80.2, 73.4, 57.8, 39.1, 28.3 and 10.9% observed after 72 h of incubation with 0.01, 0.05, 0.1, 0.5, 1 and 5 µM, respectively. The in vivo results demonstrated that HA­TPGS DOX­NPs had the highest antitumor efficacy, with 10.5% tumor inhibition efficiency after 28 days of injection. Overall, HA­TPGS DOX­NPs had significant antitumor effects and minimal systemic toxicity, and their application may be a promising strategy for the treatment of lung cancer.


Assuntos
Doxorrubicina/administração & dosagem , Glutationa/metabolismo , Ácido Hialurônico/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Vitamina E/química , Células A549 , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Neoplasias Pulmonares/metabolismo , Camundongos , Nanopartículas , Tamanho da Partícula , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Nanomedicina Teranóstica , Ensaios Antitumorais Modelo de Xenoenxerto
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