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1.
Tumour Biol ; 35(7): 6271-82, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24633889

RESUMO

MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miR-196a2 rs11614913 SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. We carried out a meta-analysis of 46 studies including 20,673 cases and 25,143 controls to assess the association between the miR-196a2 rs11614913 and cancer risk by pooled odds ratios (ORs) and 95 % confidence intervals (CIs). Overall, we found a significant association between the rs11614913 (C > T) polymorphism and cancer susceptibility (recessive model, OR = 0.89, 95 % CI = 0.81-0.98). In the stratified analysis by cancer type, significant association of cancer risk was observed in lung cancer (allelic contrast, OR = 0.89, 95 % CI = 0.82-0.97; homozygote comparison, OR = 0.79, 95 % CI = 0.67-0.94; recessive model, OR = 0.84, 95 % CI = 0.74-0.96) and liver cancer (allelic contrast, OR = 0.88, 95 % CI = 0.79-0.99; homozygote comparison, OR = 0.77, 95 % CI = 0.61-0.98; heterozygote comparison, OR = 0.84, 95 % CI = 0.74-0.95; dominant model, OR = 0.82, 95 % CI = 0.73-0.92). During further stratified analysis by ethnicity, the rs11614913 polymorphism showed statistically significant association with increased risks of cancer in Asians (heterozygote model, OR = 1.15, 95 % CI = 1.01-1.30) but not in Caucasians. This meta-analysis suggests that the miR-196a2 rs11614913 polymorphism may contribute to decreased susceptibility to cancer, especially including liver cancer and lung cancer. However, it may be a risk factor for cancer development in Asians. Larger, better studies of homogeneous cancer patients are needed to further assess the correlation between this polymorphism and cancer risk.


Assuntos
Estudos de Associação Genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Povo Asiático/genética , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , População Branca
2.
ACS Appl Mater Interfaces ; 16(36): 47429-47442, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39214567

RESUMO

Layered energetic materials (LEMs) can effectively balance energy and mechanical sensitivity, making them a current research focus in the field of energetic materials. However, the influence of the layered stacking pattern on impact sensitivity is still unclear, leading to the lack of advanced design strategies for high-energy low-sensitivity LEMs. Herein, we first utilize novel indicators such as maximum plane separation and hydrogen bond dimension to perform high-throughput screening on over 106 candidate structures, resulting in 17 target crystals. A systematic analysis was then conducted on the relationships between the bond dissociation energy (BDE) of the weakest energy-storing bond at the molecular level, the intralayer hydrogen bond energy (HBE), and the sliding energy barrier (SEB) at the crystal level with impact sensitivity. The findings suggest that a material can have low sensitivity only if at least two of the three properties perform well, and the interlayer sliding resistance can be reduced by enhancing the intermolecular hydrogen bond interactions, which reasonably explains the experimental phenomena. More importantly, we developed a prediction model for the impact sensitivity of LEMs with a coefficient of determination of 0.88. Additionally, factors affecting HBE and SEB were identified, and a linear model was established based on molecular-level feature variables. Finally, a new strategy for designing high-energy low-sensitivity LEMs was proposed, namely, empowerment at the molecular scale and desensitization at the crystal scale. This study integrates high-throughput screening, multilevel structure-property relationship analysis, and mathematical model construction, offering new perspectives for the development of novel high-energy and low-sensitivity energetic materials.

3.
Chin Med J (Engl) ; 124(10): 1524-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21740810

RESUMO

BACKGROUND: Overexpression of breast cancer-specific gene 1 (SNCG) is associated with poor prognosis in advanced breast cancer patients. This study aimed to determine the effects of SNCG knockdown in breast cancer cells by using small hairpin RNA (shRNA). METHODS: Four different SNCG shRNA oligonucleotides were designed and chemically synthesized to construct mammalian expression vectors. These vectors were then stably transfected into a breast cancer MCF-7 cell line to knockdown SNCG expression. After SNCG knockdown was confirmed, the stable cell lines were inoculated into nude mice. SNCG mRNA and protein expressions were analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively in both the stable cell lines and xenografts. RESULTS: All four SNCG shRNA constructs significantly reduced SNCG mRNA and protein levels in MCF-7 cells, as compared to the unrelated sequence control shRNA and the liposome control mice (P < 0.05). SNCG-knockdown MCF-7 cells formed significantly smaller tumor masses than cells expressing the unrelated sequence control or the liposome control mice (P < 0.05). CONCLUSION: SNCG shRNA effectively suppressed breast cancer cell formation in vivo and may be a useful clinical strategy to control breast cancer.


Assuntos
Neoplasias da Mama/terapia , RNA Interferente Pequeno/fisiologia , gama-Sinucleína/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaios Antitumorais Modelo de Xenoenxerto , gama-Sinucleína/genética
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