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1.
PLoS Pathog ; 20(6): e1012271, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38829910

RESUMO

Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.


Assuntos
Herpesvirus Humano 1 , Imunidade Inata , Humanos , Animais , Herpesvirus Humano 1/imunologia , Camundongos , Replicação Viral , Herpes Simples/imunologia , Herpes Simples/virologia , Herpes Simples/metabolismo , Transdução de Sinais , Células HEK293 , Proteínas Repressoras
2.
Growth Factors ; 42(2): 74-83, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38164009

RESUMO

Non-small cell lung cancer (NSCLC) stands prominent among the prevailing and formidable oncological entities. The immune and metabolic-related molecule Phospholipase A2, group IID (PLA2G2D) exerts promotional effects on tumor progression. However, its involvement in cancer angiogenesis remains elusive. Therefore, this investigation delved into the functional significance of PLA2G2D concerning angiogenesis in NSCLC. This study analyzed the expression and enriched pathways of PLA2G2D in NSCLC tissues through bioinformatics analysis, and measured the expression of PLA2G2D in NSCLC cells using qRT-PCR and western blot (WB). Subsequently, the viability and angiogenic potential of NSCLC cells were assessed employing CCK-8 and angiogenesis assays, respectively. The expression profile of angiogenic factors was analyzed through WB. Finally, the expression of glycolysis pathway-related genes, extracellular acidification rate and oxygen consumption rate, and the levels of pyruvate, lactate, citrate, and malate were analyzed in NSCLC cells using qRT-PCR, Seahorse XF 96, and related kits. Bioinformatics analysis revealed the upregulation of PLA2G2D in NSCLC tissues and its association with VEGF and glycolysis signaling pathways. Molecular and cellular experiments demonstrated that upregulated PLA2G2D promoted the viability, angiogenic ability, and glycolysis pathway of NSCLC cells. Rescue assays revealed that the effects of high expression of PLA2G2D on the viability, angiogenic ability, and glycolysis of NSCLC cells were weakened after the addition of the glycolysis inhibitor 2-DG. In summary, PLA2G2D plays a key role in NSCLC angiogenesis through aerobic glycolysis, displaying great potential as a target for anti-angiogenesis therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neovascularização Patológica , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/genética , Neovascularização Patológica/metabolismo , Linhagem Celular Tumoral , Glicólise , Fosfolipases A2 do Grupo II/metabolismo , Fosfolipases A2 do Grupo II/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Transdução de Sinais , Angiogênese
3.
Pharmacology ; 108(1): 8-16, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36470213

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for about 85% of generally reported lung cancer patients. OBJECTIVES: This is a systematic review of the clinical efficacy and safety of osimertinib in treating epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC. METHODS: A network search was completed for clinical research literature (from inception of each database to May 30, 2020) on osimertinib for EGFR mutation-positive advanced NSCLC. Strict inclusion and exclusion criteria were formulated to screen the literature. After data extraction, RevMan 5.3 software was utilized for quality evaluation and meta-analysis. The primary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events of grades 3 and 4. RESULTS: Finally, 6 eligible articles and a total of 1,848 patients containing 1,123 in experimental groups and 725 in control groups were included. Meta-analysis indicated that ORR (odds ratio [OR] = 3.40, 95% CI 1.64∼7.01, p = 0.0009), DCR (OR = 4.36, 95% CI 3.09∼6.15, p < 0.00001), PFS (HR = 0.36, 95% CI 0.27∼0.47, p < 0.00001), and OS (OR = 0.58, 95% CI 0.46∼0.72, p < 0.00001) of the experimental group were prominently better than the control group. Adverse events of grades 3 and 4 mainly incorporated decreased nausea, rash, stomatitis, and vomiting, which were dramatically relieved compared with the control group. CONCLUSION: Osimertinib is currently an appreciably effective and well-tolerated therapeutic avenue for EGFR mutation-positive advanced NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Compostos de Anilina/efeitos adversos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Mutação
4.
J Recept Signal Transduct Res ; 42(3): 215-224, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33719846

RESUMO

Baicalin plays important roles in different types of cancer. A previous report showed that baicalin attenuates cisplatin resistance in lung cancer. However, its mechanism remains unclear. In this study, we investigated the effect and mechanism of baicalin on DNA repair and sensitivity of lung cancer cells to cisplatin. A549 and A549/DPP cells were treated with baicalin and cisplatin. A549/DPP cells were transfected with XRCC1 and siXRCC1. Cell viability and DNA damage were detected by MTT and comet assay. Apoptosis rate and cell cycle were detected by flow cytometry assay. The expressions of Bax, Bcl-2, and Cyclin D1 were detected by western blot. XRCC1 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Baicalin and cisplatin decreased cell viability in A549 and A549/DPP cells in dose-dependent manner. Baicalin enhanced the effect of cisplatin on promoting apoptosis, arresting cell on S stage and triggering DNA damage accompanied with the upregulation of Bcl-2-associated X protein (Bax) and downregulation of B-cell lymphoma 2 (Bcl-2) and Cyclin D1 in A549/DPP cells. Moreover, baicalin promoted the inhibitory effect of cisplatin on XRCC1 expression in A549 and A549/DPP cells. However, the synthetic effects of baicalin and cisplatin on A549/DPP cells were partially inhibited by XRCC1 overexpression and promoted by XRCC1 knockdown. This study demonstrates that baicalin interferes with XRCC1-mediated cellar DNA repair to sensitize lung cancer cells to cisplatin.


Assuntos
Antineoplásicos , Flavonoides , Neoplasias Pulmonares , Proteína 1 Complementadora Cruzada de Reparo de Raio-X , Células A549 , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Ciclina D1/genética , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos/genética , Flavonoides/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
5.
Biochim Biophys Acta Proteins Proteom ; 1865(11 Pt B): 1522-1528, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28844740

RESUMO

Global functions of nicotinic acetylcholine receptors, such as subunit cooperativity and compatibility, likely emerge from a network of amino acid residues distributed across the entire pentameric complex. Identification of such networks has stymied traditional approaches to acetylcholine receptor structure and function, likely due to the cryptic interdependency of their underlying amino acid residues. An emerging evolutionary biochemistry approach, which traces the evolutionary history of acetylcholine receptor subunits, allows for rational mapping of acetylcholine receptor sequence space, and offers new hope for uncovering the amino acid origins of these enigmatic properties.


Assuntos
Evolução Molecular , Receptores Colinérgicos/química , Animais , Humanos , Estrutura Terciária de Proteína , Receptores Colinérgicos/metabolismo , Relação Estrutura-Atividade
6.
Opt Express ; 24(11): 12293-300, 2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27410144

RESUMO

We present a deterministic scheme for generating large-scale atomic W states in a cavity QED system via a simple expansion mechanism, which is realized only by a detuned interaction between two identical atoms and a vacuum cavity mode. With the presented scheme, a W-type Bell pair can be created and an n-atom W state can be expanded to a 2n-atom W state with a unit probability of success in principle. No multi-atom gates, quantum memories or quantum non-demolition measurements are required, greatly simplifying the experimental realization of the scheme. The feasibility analysis shows that our expansion scheme can be implemented with state-of-the-art technologies. Our scheme enables advances not only in quantum information and communication but also in quantum thermodynamics, where atomic W states plays a crucial role.

7.
Opt Express ; 24(24): 27319-27330, 2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27906304

RESUMO

An optical scheme for simulating nonlocality distillation is proposed in post-quantum regime. The nonlocal boxes are simulated by measurements on appropriately pre- and post-selected polarization entangled photon pairs, i.e. post-quantum nonlocality is simulated by exploiting fair-sampling loophole in a Bell test. Mod 2 addition on the outputs of two nonlocal boxes combined with pre- and post-selection operations constitutes the key operation of simulating nonlocality distillation. This scheme provides a possible tool for the experimental study on the nonlocality in post-quantum regime and the exact physical principle precisely distinguishing physically realizable correlations from nonphysical ones.

8.
Tumour Biol ; 35(2): 1619-25, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24078465

RESUMO

The cytostatic drug from traditional Chinese medicinal herb has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Oxymatrine, classified as a quinolizidine alkaloid, is a phytochemical product derived from Sophora flavescens, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma MNNG/HOS cell have not been well studied. In the present study, the cytotoxic effects of oxymatrine on MNNG/HOS cells were examined by MTT and bromodeoxyuridine (BrdU) incorporation assays. The percentage of apoptotic cells and the level of mitochondrial membrane potential (Δψ m) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by Western blot analysis or enzyme assay Kit. Our results showed that treatment with oxymatrine resulted in a significant inhibition of cell proliferation and DNA synthesis in a dose-dependent manner, which has been attributed to apoptosis. Furthermore, we found that oxymatrine considerably inhibited the expression of Bcl-2 whilst increasing that of Bax. This promoted mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the activation of caspase-9 and -3. Moreover, addition of oxymatrine to MNNG/HOS cells also attenuated phosphatidylinositol 3-kinase (PI3K) /Akt signaling pathway cascade, evidenced by the dephosphorylation of P13K and Akt. Likewise, oxymatrine significantly suppressed tumor growth in female BALB/C nude mice bearing MNNG/HOS xenograft tumors. In addition, no evidence of drug-related toxicity was identified in the treated animals by comparing the body weight increase and mortality. Therefore, these findings should be useful for understanding the apoptotic cellular mechanism mediated by oxymatrine and might offer a therapeutic potential advantage for human osteosarcoma chemoprevention or chemotherapy.


Assuntos
Alcaloides/farmacologia , Apoptose/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Quinolizinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alcaloides/química , Animais , Proliferação de Células/efeitos dos fármacos , DNA/biossíntese , DNA/efeitos dos fármacos , Elafina/metabolismo , Feminino , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Proteína Oncogênica v-akt/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , Quinolizinas/química , Sophora/química , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Tumour Biol ; 35(4): 3119-23, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24323562

RESUMO

Osteosarcoma is the most common form of primary malignant bone tumor that mainly occurs in juvenile patients. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that p21 plays important roles in regulating tumor growth. To study the effects of p21 on the chemosensitivity of human osteosarcoma U2OS cells to cisplatin and its relevant mechanisms, we stably transfect the pC-21-SN3 vector containing P21 to U2O3 cells (U2O3-p21), which was identified by RT-PCR and Western blot. The results showed that no p21 was expressed in U2OS and U2OS-vec cells, but it was highly expressed in U2O3-p21 cells at mRNA and protein levels. The growth of U2OS cells was almost not influenced by p21 alone. However, U2O3-p21 cells underwent more obvious apoptotic morphological changes than U2OS and U2OS-vec cells after being treated with cisplatin (5 µg) for 72 h. Besides, increased expression of cleaved caspase-3 and Bax/Bcl-2 ratio was observed in cisplatin-treated U2O3-p21 cells. These data clearly indicated that exogenous p21 gene transfection could enhance the cisplatin-induced cytotoxicity against human osteosarcoma U2OS cells, at least in part, by activating caspase-3 cascade and increasing Bax/Bcl-2 ratio.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Caspase 3/metabolismo , Cisplatino/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/fisiologia , Osteossarcoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína X Associada a bcl-2/análise , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Osteossarcoma/patologia
10.
Mol Biol Rep ; 41(4): 2679-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24449364

RESUMO

The C3435T polymorphism of the multidrug resistance gene (MDR1) has been implicated in inflammatory bowel disease (IBD) risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of IBD using all case-control studies published before February 2013 according to PubMed and Web of Science. A total of 13 case-control studies, including 6,757 cases and 4,295 controls, were included. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Overall, no evidence has indicated that the C3435T polymorphism was associated with the susceptibility to IBD (dominant model: OR = 1.05, 95 % CI: 0.96-1.16; CT vs. CC: OR = 1.06, 95 % CI: 0.95-1.17; TT vs. CC: OR = 1.04, 95 % CI: 0.92-1.17; recessive model: OR = 0.99, 95 % CI: 0.90-1.09). Besides, stratified analysis by clinical type also indicated that no significant association between MDR1 C3435T and the risk of Crohn's disease and ulcerative colitis was observed. This meta-analysis indicated that the C3435T polymorphism of MDR1 may not confer susceptibility to IBD.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Humanos , Razão de Chances , Viés de Publicação , Risco
11.
J Gastroenterol Hepatol ; 29(7): 1396-405, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24548122

RESUMO

BACKGROUND AND AIM: The adiponectin polymorphism has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD), but the results remain inconclusive. The aim of this meta-analysis is to investigate the association between adiponectin polymorphisms and NAFLD risk. METHODS: All eligible case-control studies published up to September 2013 were identified by searching PubMed, Web of Science, and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model. RESULTS: A total of 10 case-control studies were included; of those, there were nine studies (1223 cases and 1580 controls) for +45T>G polymorphism, seven studies (876 cases and 989 controls) for +276G>T polymorphism, and three studies (299 cases and 383 controls) for -11337C>G polymorphism. Overall, a significantly increased risk was found for +45T>G and -11377C>G polymorphism (+45T>G: OR = 1.45, 95% CI: 1.06-2.00 for recessive model, OR = 1.48, 95% CI: 1.07-2.06 for GG vs TT; -11377C>G: OR = 1.52, 95% CI: 1.10-2.09 for dominant model, OR = 3.88, 95% CI: 1.29-11.68 for GG vs CC), while for +276G>T polymorphism, we found a significantly decreased risk between them (OR = 0.65, 95% CI: 0.45-0.94 for recessive model, OR = 0.58, 95% CI: 0.40-0.84 for TT vs GG). In subgroup analysis by ethnicity, significant association was detected among Asians for +276G>T polymorphism, but not for +45T>G polymorphism. Besides, none of the three adiponectin polymorphisms was associated with the serum adiponectin levels. CONCLUSION: This meta-analysis suggests that adiponectin +45T>G and -11377C>G polymorphisms might be a risk factor for NAFLD, while +276G>T polymorphism may be a protective factor for NAFLD among Asians.


Assuntos
Adiponectina/genética , Predisposição Genética para Doença/genética , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo Genético/genética , Povo Asiático/genética , Estudos de Casos e Controles , Bases de Dados Bibliográficas , Humanos , Fatores de Proteção , Fatores de Risco
12.
PLoS One ; 19(1): e0296660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38241276

RESUMO

Exploring the of regional tourism efficiency is of great significance in promoting high-quality development of regional tourism. However, there are not many studies that measure the quality development of tourism destinations from the perspective of inputs and output. Based on this, the data envelopment analysis model is used to measure the overall technical efficiency (TECRS), pure technical efficiency (TEVRS), and scale efficiency (SE) with the help of DEA-SOLVER software, taking the ten prefecture-level cities in Shaanxi Province as examples, to further analyze and evaluate the spatial differences of different tourism destinations and the reasons for the differences. The results of the study found that: the efficiency indicators explain the differences in the development quality of tourism destinations from different sides; the development quality of tourism destinations in Shaanxi as a whole is low, with excessive inputs and insufficient outputs; and the tourism destinations with relatively high development quality are distributed in the Guanzhong. On this basis, corresponding countermeasure suggestions are put forward to promote the improvement of governance efficiency of tourism destinations in Shaanxi Province, and then optimize the quality of development.


Assuntos
Eficiência , Turismo , Humanos , Cidades , China , Desenvolvimento Econômico
13.
Mol Biotechnol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619801

RESUMO

N6-methyladenosine (m6A) is a common posttranscriptional RNA modification and plays an important role in cancer biology. Circular RNAs (circRNAs) are also reported to participate in lung adenocarcinoma (LUAD) progression. Here, we aimed to investigate the functions of Wilms tumor 1-associating protein (WTAP) methyltransferase and circEEF2 in LUAD cell tumorigenesis, and probe whether circEEF2 functioned through WTAP-induced m6A modification and its potential mechanisms. Functional analyses were conducted by tube formation, sphere formation, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays in vitro as well as tumor formation experiments in mice, respectively. The N6-methyladenine (m6A) modification in circEEF2 mRNA was determined by RNA immunoprecipitation (Me-RIP) assay. The interaction between IGF2BP2 (Insulin Like Growth Factor 2 MRNA-Binding Protein 2) and circEEF2 or Calcium-activated nucleotidase 1 (CANT1) mRNA was confirmed using RIP assay. LUAD tissues and cells showed high circEEF2 expression, and the deficiency of circEEF2 suppressed LUAD cell angiogenesis, stemness, proliferation, migration, and invasion. WTAP induced circEEF2 m6A modification. WTAP silencing repressed the oncogenic phenotypes of LUAD cells via stabilizing circEEF2 in an m6A-dependent manner. IGF2BP2 interacted with circEEF2 and CANT1, and WTAP and circEEF2 could regulate CANT1 expression through IGF2BP2. The inhibition of LUAD cell oncogenic phenotypes caused by circEEF2 deficiency was abolished by CANT1 overexpression. In addition, WTAP silencing impeded LUAD growth via modulating circEEF2 and CANT1 in vivo. WTAP-mediated m6A modification of circEEF2 promotes lung adenocarcinoma growth and tumorigenesis by stabilizing CANT1 through IGF2BP2.

14.
Curr Protein Pept Sci ; 25(5): 386-393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38265409

RESUMO

BACKGROUND: Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression. METHODS: Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ ß-catenin signaling pathway were detected by western blot. RESULTS: Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/ß-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/ß-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/ß-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8. CONCLUSION: Collectively, these data demonstrated that CBX8 induced EMT through Wnt/ß-- catenin signaling, driving migration and invasion of LC cells.


Assuntos
Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Complexo Repressor Polycomb 1 , Via de Sinalização Wnt , Transição Epitelial-Mesenquimal/genética , Humanos , Via de Sinalização Wnt/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Movimento Celular/genética , Proliferação de Células/genética , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Linhagem Celular Tumoral , Invasividade Neoplásica , beta Catenina/metabolismo , beta Catenina/genética , Técnicas de Silenciamento de Genes , Células A549
15.
Discov Med ; 36(180): 82-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273748

RESUMO

BACKGROUND: X-ray repair cross complementing 1 (XRCC1) rs1799782 polymorphism is associated with an increased risk of lung cancer (LC). The aim of this study is to analyze the underlying biological mechanisms. METHODS: Dual luciferase reporter assay was utilized to verify the impact of XRCC1 polymorphism upon promoter activity of XRCC1. Cell counting kit-8 (CCK-8) assay, colony formation assay, senescence-associated beta-galactosidase (SA-ß-gal) staining, and immunofluorescent staining were used to assess the viability, proliferation, senescence, and DNA damage of LC cells. Senescence-related proteins (cyclin dependent kinase inhibitor 1A (P21) and eukaryotic translation elongation factor 1-alpha (EF1A)) were quantified by Western blot. Chromatin immunoprecipitation was applied to validate the binding affinity of forkhead box A1 (FOXA1) and XRCC1. FOXA1-specific short hairpin RNA (shFOXA1) was used to perform the rescue assay. RESULTS: In LC cells, XRCC1 rs1799782 promoted viability and proliferation, inhibited senescence, and resulted in upregulation of EF1A as well as downregulation of P21 and phosphorylated H2A.X variant histone (γH2AX). XRCC1 rs1799782 promoted FOXA1-mediated transcription of XRCC1 through enhancing its binding to FOXA1. shFOXA1 counteracted the effects of XRCC1 rs1799782 upon the viability, proliferation, and senescence of LC cells. CONCLUSIONS: XRCC1 rs1799782 promotes DNA damage repair in LC cells through enhancing its binding to FOXA1, which facilitates FOXA1-mediated transcription of XRCC1.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Proteínas de Ligação a DNA/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Polimorfismo Genético , Dano ao DNA , Reparo do DNA/genética , Fator 3-alfa Nuclear de Hepatócito/genética
16.
J Microbiol Biotechnol ; 34(2): 249-261, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419324

RESUMO

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Lanosterol/análogos & derivados , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Ácido Micofenólico/farmacologia , Antineoplásicos/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carboxilesterase
17.
J Pharm Pharmacol ; 76(4): 354-367, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38330446

RESUMO

OBJECTIVES: Reportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung cancer cells. METHODS: After the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative reverse transcription PCR (qRT-PCR). The DDP-resistant lung cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A. RESULTS: GA-A suppressed the viability, migration, and invasion while downregulating Beclin and autophagy marker LC3II/LC3I levels and upregulating P62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the apoptosis and regulated the circFLNA/miR-486-3p/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung cancer tumor growth and blocked autophagy. CONCLUSION: GA-A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to DDP.


Assuntos
Antineoplásicos , Autofagia , Carcinoma Pulmonar de Células não Pequenas , Ácidos Heptanoicos , Lanosterol , Neoplasias Pulmonares , MicroRNAs , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Citocromo P-450 CYP1A1/efeitos dos fármacos , Citocromo P-450 CYP1A1/metabolismo , Resistencia a Medicamentos Antineoplásicos , Ácidos Heptanoicos/farmacologia , Ácidos Heptanoicos/uso terapêutico , Lanosterol/análogos & derivados , Lanosterol/farmacologia , Lanosterol/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/efeitos dos fármacos , MicroRNAs/metabolismo , RNA Circular/efeitos dos fármacos , RNA Circular/metabolismo , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/efeitos dos fármacos , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/metabolismo
18.
Am J Clin Nutr ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38795741

RESUMO

BACKGROUND: Our previous studies showed that curcumin prevented hepatic steatosis in animal models. OBJECTIVES: This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). METHODS: In a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. RESULTS: Curcumin consumption significantly reduced CAP value compared with placebo (-17.5 dB/m; 95% confidence interval [CI]: -27.1, -7.8 dB/m; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95% CI: -4.4, -0.8 kg; P < 0.001) and BMI (-1.0 kg/m2; 95% CI: -2.0, -0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95% CI: -0.20, -0.04 mmol/L; P = 0.004), triglycerides (-0.29 mmol/L; 95% CI: -0.41, -0.14 mmol/L; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95% CI: -0.12, -0.01 mmol/L; P = 0.038), hemoglobin A1c (-0.06%; 95% CI: -0.33, -0.01%; P = 0.019), and insulin (-4.94 µU/L; 95% CI: -9.73, -0.15 µU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). CONCLUSIONS: Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn as ChiCTR2200058052.

19.
Radiat Oncol ; 19(1): 72, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851718

RESUMO

BACKGROUND: To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT). METHODS: Total of 143 EC patients in the authors' hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated. RESULTS: Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively. CONCLUSION: CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.


Assuntos
Neoplasias Esofágicas , Nomogramas , Pneumonite por Radiação , Humanos , Neoplasias Esofágicas/radioterapia , Pneumonite por Radiação/etiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Prognóstico , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios X , Radiômica
20.
Cancer Biother Radiopharm ; 38(5): 322-335, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33769841

RESUMO

Background: Mesenchymal stem cells (MSCs) could inhibit the proliferation of lung cancer cells. The authors' study investigated the effects of immunologically activated human umbilical cord (HUC)-MSCs on A549 lung cancer cells. Materials and Methods: HUC-MSCs were separated from the umbilical cord using the adherence method. Surface markers of HUC-MSCs were detected by flow cytometry for MSC identification. Imiquimod (TLR7 agonist) was incubated with HUC-MSCs for immune activation, and the expression of MSC-specific markers and immune inflammatory molecules was measured by quantitative real-time polymerase chain reaction. HUC A549 cells were cocultured with HUC-MSCs treated with imiquimod, siTLR7 (small interfering RNA for TLR7) or TLR7 overexpression, and then cell viability, proliferation, migration, and invasion, and the expression of phosphatidylinositol-3-kinase (PI3K)/Akt and NF-κB was investigated using MTT assay, clone formation assay, transwell assay, and Western blot, respectively. Results: HUC-MSCs were identified as positive for CD73, CD105, CD44, CD29, and CD90. Expression of MSC markers was inhibited, while those of immune inflammatory molecules expression except IL-6 (interleukin-6) was enhanced after MSCs were immunologically activated by imiquimod. After being cocultured with HUC-MSCs treated with imiquimod or overexpressed TLR7, cell viability, proliferation, and metastasis, and the phosphorylation of P65 and AKT in A549 cells were decreased, but apoptosis was increased, while siTLR7 showed the opposite effect HUC. Conclusions: Immunologically activated HUC-MSCs inhibited the growth and metastasis, yet, promoted the apoptosis of A549 lung cancer cells via regulating the PI3K/Akt and NF-κB pathways.


Assuntos
Neoplasias Pulmonares , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Diferenciação Celular , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Imiquimode/farmacologia , Imiquimode/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor 7 Toll-Like/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neoplasias Pulmonares/metabolismo
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