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1.
Small ; 18(5): e2104401, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34825486

RESUMO

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

2.
BMC Cardiovasc Disord ; 22(1): 2, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991490

RESUMO

INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.


Assuntos
Hipertensão/complicações , Hiperuricemia/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Ácido Úrico/sangue , Idoso , China/epidemiologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hiperuricemia/sangue , Hiperuricemia/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais
4.
Mol Ther ; 25(3): 739-751, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28131418

RESUMO

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Canal de Potássio ERG1/genética , Epigênese Genética , Inativação Gênica , Neoplasias Pulmonares/genética , Pseudogenes/genética , Proteína rhoB de Ligação ao GTP/genética , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Análise por Conglomerados , Canal de Potássio ERG1/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Histona Desmetilases/metabolismo , Humanos , Neoplasias Pulmonares/mortalidade , Prognóstico , Ligação Proteica , Proteína rhoB de Ligação ao GTP/metabolismo
5.
Mol Cancer ; 16(1): 17, 2017 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-28109288

RESUMO

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.


Assuntos
Adenocarcinoma/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , Interleucinas/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Análise por Conglomerados , Biologia Computacional/métodos , Modelos Animais de Doenças , Expressão Ectópica do Gene , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Perfilação da Expressão Gênica , Inativação Gênica , Histona Desmetilases/genética , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , Carga Tumoral
6.
Am J Ther ; 24(6): e659-e666, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26488362

RESUMO

In this study, a randomized trial was conducted to compare the clinical effectiveness of proximal femoral locking compression plate (PFLCP), dynamic hip screw (DHS), and proximal femoral nail antirotation (PFNA) for unstable intertrochanteric femoral fracture treatment. Ninety patients diagnosed with unstable intertrochanteric femoral fracture were enrolled in this study at the department of orthopedics at Linyi Second People's Hospital between May 2010 and May 2012. Fractures were classified according to Tronzo-Evans classification, and the patients were randomly divided into 3 groups, PFLCP, DHS, and PFNA, with 30 patients in each group. The length of incision, operative time, intraoperative blood loss, postoperative drainage, postoperative weight-bearing ambulation time, and duration of fracture union were significantly lower in patients who underwent PFNA and PFLCP compared to patients treated with DHS. Furthermore, when the same clinical parameters were used for comparison, the PFNA group showed markedly lower values compared with the PFLCP group. The total incidence of postoperative complications was significantly different among the PFNA, PFLCP, and DHS groups, with the PFNA group exhibiting markedly lower complication rates compared with PFLCP and DHS groups. However, PFLCP and DHS groups did not show significant differences in the incidence of postoperative complications. Notably, the Harris hip score of PFNA group was markedly higher than the DHS group. In conclusion, our results provide convincing evidence that PFNA may be the most effective internal fixation treatment of unstable intertrochanteric femoral fracture.


Assuntos
Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Pinos Ortopédicos , Placas Ósseas , Parafusos Ósseos , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Incidência , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Fatores de Tempo , Resultado do Tratamento
7.
Tumour Biol ; 37(6): 7693-701, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26692098

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in the development of several human cancers. MIR31HG, an lncRNA located in 9p21.3 and 2166 bp in length, has been found to be upregulated in breast cancer and contributes to cell proliferation and invasion. However, the expression pattern and biological function of MIR31HG in gastric cancer are still not well documented. In this study, we found that MIR31HG expression is decreased in gastric cancer tissues and associated with larger tumor size and advanced pathological stage. Patients with lower MIR31HG expression had a relatively poor prognosis. Furthermore, ectopic over-expression of MIR31HG could inhibit gastric cancer (GC) cell proliferation both in vitro and in vivo, while knockdown of MIR31HG by small interfering RNA (siRNA) promoted cell proliferation in GC cells partly via regulating E2F1 and p21 expression. Our findings present that decreased MIR31HG is involved in GC development and could be identified as a poor prognostic biomarker in GC patients.


Assuntos
Carcinoma/genética , MicroRNAs/genética , RNA Neoplásico/genética , Neoplasias Gástricas/genética , Animais , Carcinoma/mortalidade , Carcinoma/patologia , Divisão Celular , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Fator de Transcrição E2F1/biossíntese , Fator de Transcrição E2F1/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/análise , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Prognóstico , Interferência de RNA , RNA Neoplásico/análise , RNA Neoplásico/antagonistas & inibidores , RNA Interferente Pequeno/genética , Proteínas Recombinantes de Fusão/metabolismo , Organismos Livres de Patógenos Específicos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carga Tumoral
8.
Zhonghua Bing Li Xue Za Zhi ; 45(2): 91-6, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-26879429

RESUMO

OBJECTIVE: To study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors. METHODS: The clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors. RESULTS: Sixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05). CONCLUSIONS: The pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.


Assuntos
Transplante de Rim , Rim/patologia , Adulto , Fatores Etários , Biópsia , Cadáver , Criança , Rejeição de Enxerto/patologia , Humanos , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Infarto/patologia , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Necrose , Tacrolimo/efeitos adversos , Transplante Homólogo , Resultado do Tratamento
9.
J Transl Med ; 13: 250, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26238992

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis. METHODS: QRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4-IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student's t test (two-tailed). RESULTS: SPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial-mesenchymal transition (EMT) process. CONCLUSION: Low expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer.


Assuntos
Transição Epitelial-Mesenquimal/genética , Metástase Linfática/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/metabolismo , Análise de Sobrevida
10.
Tumour Biol ; 36(5): 3521-31, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25549794

RESUMO

Homeobox genes, a superfamily of evolutionarily conserved developmental genes, function as critical master regulatory factors in controlling body plan specification and cell fate determination. Recently, a substantial body of evidence indicates that the aberrant Homeobox (HOX) genes also play key roles in the development of cancers. Many reports have shown not only that HOX gene expression is upregulated or downregulated in many cancers but also that the expression of specific HOX genes tends to differ based on tissue type. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation, and its expression is also downregulated in many cancers mediated by DNA methylation. However, its biological role and clinical significance in nonsmall cell lung cancer (NSCLC) development and progression are not well documented. In this study, we found that expression levels of HOXA5 were significantly decreased in NSCLC tissues compared with adjacent normal tissues. Its expression level was significantly correlated with tumor-node-metastasis (TNM) stages, tumor size, and lymph node metastasis. Moreover, patients with lower levels of HOXA5 expression had a relatively poor prognosis. Furthermore, ectopic overexpression of HOXA5 could inhibit cell proliferation and invasion, while knockdown HOXA5 by siRNA promoted cell proliferation in NSCLC cells partly via regulating p21 expression. Our findings present that decreased HOXA5 could be identified as a poor prognostic biomarker in NSCLC and regulate cell proliferation and invasion.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Homeodomínio/biossíntese , Proteínas rho de Ligação ao GTP/biossíntese , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Homeodomínio/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , Proteínas rho de Ligação ao GTP/genética
11.
Mol Cancer ; 13: 92, 2014 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-24775712

RESUMO

BACKGROUND: Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. METHODS: HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. RESULTS: HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. CONCLUSIONS: HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Animais , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Dados de Sequência Molecular , Transplante de Neoplasias , RNA Longo não Codificante/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Microambiente Tumoral
12.
Mol Cancer ; 13: 68, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24655544

RESUMO

BACKGROUND: Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear. METHODS: Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry. RESULTS: BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression. CONCLUSION: We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas B-raf/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Apoptose/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Movimento Celular/fisiologia , Regulação para Baixo , Citometria de Fluxo , Xenoenxertos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Tumour Biol ; 35(8): 7587-94, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24793017

RESUMO

Long non-coding RNAs (lncRNAs) have emerged as major players in governing fundamental biological processes, and many of which are misregulated in multiple cancers and likely to play a functional role in tumorigenesis. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. lncRNA associated with microvascular invasion in HCC (lncRNA MVIH) was found to be generally upregulated in HCC. Moreover, MVIH overexpression could serve as an independent risk factor to predict poor RFS and promote tumor growth and metastasis via activating angiogenesis. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression is unknown. In this study, we found that lncRNA MVIH levels were increased in NSCLC tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, tumor size, and lymph node metastasis. Moreover, patients with high levels of MVIH expression had a relatively poor prognosis. Furthermore, knockdown of MVIH expression by siRNA could inhibit cell proliferation and invasion, while ectopic expression of MVIH promoted cell proliferation and invasion in NSCLC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that increased lncRNA MVIH could be identified as a poor prognostic biomarker in NSCLC and regulate cell proliferation and invasion.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico
14.
Cell Death Dis ; 15(1): 12, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182561

RESUMO

Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Humanos , Citocinas , Pulmão , Metionina/farmacologia , Racemetionina , Microambiente Tumoral
15.
J Agric Food Chem ; 71(1): 963-973, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36548634

RESUMO

Ginsenosides, the main bioactive ingredients of the Panax genus, are dammarane or oleanane triterpenoids with glycosylated modifications at C3/C6/C20 hydroxyls or C28 carboxyl, and their diverse glycosylation pattern has attracted great attention. However, the biosynthesis of some important saponins is still unclear. In this study, six UGTs were characterized, two of which were novel. PnUGT71A3 catalyzes not only the C6 hydroxyl glycosylation of protopanaxatriol (PPT) and F1 to form Rh1 and Rg1, respectively, but also the C20 hydroxyl glycosylation of protopanaxadiol (PPD)-type Rg3 to generate Rd. Especially, PnUGT94M1 is UDP-ß-l-rhamnose (UDP-Rha)-dependent, regioselectively catalyzing the C2' hydroxyl rhamnosylation of C6 glucose of the PPT-type ginsenosides Rg1 and Rh1 to generate ginsenosides Re and Rg2, respectively. Site-directed mutagenesis showed that His21, Asp120, Ser363, and Pro372 are key residues, and the triple mutant (G344S/G345S/L346T) highly improved the activity toward Rg1 and Rh1. The findings in this study, perfect main ginsenosides biosynthetic pathways in the Panax genus, expand the biocatalyst toolbox for ginsenoside production and show that the PSPG motif is one of the options to modify UGTs to improve their activities.


Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Glicosiltransferases/metabolismo , Panax notoginseng/metabolismo , Vias Biossintéticas , Glicosilação , Panax/química
16.
Cell Death Dis ; 14(7): 475, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37500615

RESUMO

The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3'UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Fosfofrutoquinase-2 , Proteína 1 de Ligação a Y-Box , Humanos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Chaperonina com TCP-1/metabolismo , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fosfofrutoquinase-2/genética , Monoéster Fosfórico Hidrolases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Proteínas de Ligação a RNA/genética
17.
PeerJ ; 11: e14984, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187528

RESUMO

Objective: As the primary means of plant-induced haploid, anther culture is of great significance in quickly obtaining pure lines and significantly shortening the potato breeding cycle. Nevertheless, the methods of anther culture of tetraploid potato were still not well established. Methods: In this study, 16 potato cultivars (lines) were used for anther culture in vitro. The corresponding relation between the different development stages of microspores and the external morphology of buds was investigated. A highly-efficient anther culture system of tetraploid potatoes was established. Results: It was shown in the results that the combined use of 0.5 mg/L 1-Naphthylacetic acid (NAA), 1.0 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), and 1.0 mg/L Kinetin (KT) was the ideal choice of hormone pairing for anther callus. Ten of the 16 potato cultivars examined could be induced callus with their respective anthers, and the induction rate ranged from 4.44% to 22.67% using this hormone combination. According to the outcome from the orthogonal design experiments of four kinds of appendages, we found that the medium with sucrose (40 g/L), AgNO3 (30 mg/L), activated carbon (3 g/L), potato extract (200 g/L) had a promotive induction effect on the anther callus. In contrast, adding 1 mg/L Zeatin (ZT) effectively facilitated callus differentiation. Conclusion: Finally, 201 anther culture plantlets were differentiated from 10 potato cultivars. Among these, Qingshu 168 and Ningshu 15 had higher efficiency than anther culture. After identification by flow cytometry and fluorescence in situ hybridization, 10 haploid plantlets (5%), 177 tetraploids (88%), and 14 octoploids (7%) were obtained. Some premium anther-cultured plantlets were further selected by morphological and agronomic comparison. Our findings provide important guidance for potato ploidy breeding.


Assuntos
Solanum tuberosum , Solanum tuberosum/genética , Tetraploidia , Hibridização in Situ Fluorescente , Melhoramento Vegetal , Hormônios
18.
Polymers (Basel) ; 14(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36432936

RESUMO

Advanced organic vapor sensors that simultaneously have high sensitivity, fast response, and good reproducibility are required. Herein, flexible, robust, and conductive vapor-grown carbon fibers (VGCFs)-filled polydimethylsiloxane (PDMS) porous composites (VGCFs/PDMS sponge (CPS)) with multilevel pores and thin, rough, and hollows wall were prepared based on the sacrificial template method and a simple dip-spin-coating process. The optimized material showed outstanding mechanical elasticity and durability, good electrical conductivity and hydrophobicity, as well as excellent acid and alkali tolerance. Additionally, CPS exhibited good reproducible sensing behavior, with a high sensitivity of ~1.5 × 105 s-1 for both static and flowing organic vapor, which was not affected in cases such as 20% squeezing deformation or environment humidity distraction (20~60% RH). Interestingly, both the reproducibility and sensitivity of CPS were better than those of film-shaped VGCFs/PDMS (CP), which has a thickness of two hundred microns. Therefore, the contradiction between the reproducibility and high sensitivity was well-solved here. The above excellent performance could be ascribed to the unique porous structures and the rough, thin, hollow wall of CPS, providing various gas channels and large contact areas for organic vapor penetration and diffusion. This work paves a new way for developing advanced vapor sensors by optimizing and tailoring the pore structure.

19.
Luminescence ; 26(4): 289-95, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20629043

RESUMO

The Cu(2+)-imprinted cross-linked chitosan resin was synthesized and the binding characteristic of the resin to Cu(2+) was evaluated. The prepared resin was packed into a micro-glass column and used as micro-separating column. The micro-separating column was connected into the chemiluminescence flow system and placed in front of the window of the photomultiplier tube. Based on the luminol-hydrogen peroxide chemiluminescence system, a flow injection online chemiluminescence method for determination of trace copper was developed and trace Cu(2+) in complex samples was successfully determined. The proposed method improved the shortcomings of chemiluminescence method's poor selectivity.


Assuntos
Quitosana/química , Resinas Compostas/química , Cobre/análise , Reagentes de Ligações Cruzadas/química , Luminescência , Impressão Molecular , Quitosana/síntese química , Resinas Compostas/síntese química , Análise de Injeção de Fluxo/instrumentação , Medições Luminescentes/instrumentação
20.
Folia Neuropathol ; 59(3): 249-262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34628790

RESUMO

Major depressive disorder (MDD) is a heterogeneous disease, involving multiple mechanisms and factors, which commonly result in injury to the psychosocial function of the central nervous system, and even suicidality of patients. However, effective treatment for MDD is still lacking. Oleuropein is a newly discovered natural compound extracted from olive leaves, which has a strong antioxidative effect by reducing the production of reactive oxygen species (ROS). Oleuropein also reduces blood pressure in humans and experimental animals, and protects blood vessels. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which supports the function of the central nervous system. BDNF plays an important role in the development of the nervous system via the regulation of cellular differentiation, survival neurogenesis and synaptic plasticity; therefore, we hypothesized that overexpression of BDNF might contribute to the therapeutic effect of oleuropein. Here, we first demonstrated that oleuropein reverses depressive-like behaviour and restores the inflammatory response in a mouse lipopolysaccharide (LPS) model of MDD. We further established a cell model of BDNF overexpression and inhibition in SH-SY5Y cells, and found that the concentration of intercellular calcium was increased after treatment with oleuropein combined with BDNF overexpression, which may be mediated by the BDNF-TrkB-CaMKII signalling pathway. In addition, we observed that the expression of neurotrophic factors, including epidermal growth factor (EGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), was increased, which may be mediated by inhibition of the RhoA-ROCK signalling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Transtorno Depressivo Maior , Animais , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Glucosídeos Iridoides , Lipopolissacarídeos/toxicidade , Camundongos
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