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Birefringent crystals have important applications in optoelectronics areas due to their ability to modulate and polarize light. Despite increasing discovery of the birefringence potential of new crystals, it remains a great challenge to optimize both birefringence and bandgap simultaneously. Herein, a 1D chain-like hybrid perovskite birefringent crystal designed by 3D-to-1D dimensional tailoring, (GAM)2 PbI7 ·H2 O (GAM = C5 N10 H10 ), is presented, showing enlarged birefringence of 0.49@550 nm and enlarged optical bandgap (2.48 eV). Consequently, the birefringent quality factor of (GAM)2 PbI7 ·H2 O is up to 2.8 times that of the template MAPbI3 . In particular, the birefringence is much larger than those of commercial birefringent crystals and surpasses that of the vast majority of hybrid perovskite known to date. Theoretical calculations reveal that the strongly anisotropic arrangement of (GAM)2.5+ π-conjugated cations and ordered PbI6 octahedra contributes to the large birefringence and wide bandgap of (GAM)2 PbI7 ·H2 O. It is believed that this work will provide a new pathway toward the rational design and synthesis of hybrid perovskite birefringent crystals for compact wide-bandgap polarization dependent devices.
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Birefringence is an important linear optical property of anisotropic crystals that plays a significant role in regulating light polarization. A new bialkali-rare earth metal sulfate, NaRbY2(SO4)4 compound, consisting of non-π-conjugated alkali metals and rare earth metal-centered dodecahedral YO8 has been synthesized. The structure analysis suggests that the three-dimensional (3D) structure of the compound is found to be attributable to the combination of dodecahedral YO8 and tetrahedral SO4 groups with Na+ and Rb+ located in the cavities. The ultraviolet, visible, and near-infrared (UV-vis-NIR) spectra reveal that the compound exhibits transparency at a wavelength of less than 200 nm. The observed birefringence of the compound is 0.045@550 nm, which is comparatively larger than that of most deep-ultraviolet (DUV) birefringent crystals. The birefringence mainly originated from the YO8 dodecahedron, which is suggested by first-principles calculations. This research work can provide a useful perspective to explore new DUV sulfates with excellent birefringence.
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INTRODUCTION: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. METHODS: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. RESULTS: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson's disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap ("older" BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap ("younger" BioAge than expected). CONCLUSIONS: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.
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Diabetes Mellitus , Nefropatias , Animais , Bovinos , Humanos , Idoso , Estudos Longitudinais , Canadá/epidemiologia , Envelhecimento , Estilo de VidaRESUMO
BACKGROUND: To assess the predictive values of primary tumor FDG uptake for patients with inoperable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). METHODS: A total of 107 patients with diagnosis of stage III NSCLC and CCRT were enrolled. The tumor maximum uptake value (SUVmax) was standardized by calculating several ratios between tumor and each background tissues. The receiver operating characteristics curve (ROC) was used to compare the predictive power of prognostic models. The tumor objective response rate (ORR) and overall survival (OS) were compared and analyzed by the Kaplan-Meier method and univariate and multivariate Cox regression models. RESULTS: The areas under ROC curve (AUCs) ranged from 0.72 to 0.81 among these tumor SUVmax and standardized SUVmax ratios, and the tumor SUVmax and tumor SUVmax-to-liver SUVmean ratio (TLMR) were more predictive of ORR (AUC, 0.81; 95% CI, 0.73-0.88 for tumor SUVmax and AUC, 0.84; 95%CI, 0.76-0.91 for TLMR) than any of other SUVmax ratios. The patients with lower tumor SUVmax, SUVmean and SUVmax ratios had a significantly better OS than those with their corresponding higher ones. Moreover, both univariate and multivariable analyses revealed that TLMR was significantly associated with better ORR and OS after adjustment with other prognostic variables. CONCLUSIONS: TLMR, a standardized tumor SUVmax, was an independent prognostic predictor for tumor ORR and OS of patients with stage III NSCLC after CCRT.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Compostos Radiofarmacêuticos , Prognóstico , Fígado/patologia , Estudos RetrospectivosRESUMO
Common nonlinear optical (NLO) crystals consist of traditional functional building blocks with inherent optical limitation. Herein, inspired by traditional (B3 O6 )3- inorganic building block, we theoretically identified a new type of organic functional building blocks and then successfully synthesized the first cyamelurate NLO crystal, Ba(H2 C6 N7 O3 )2 â 8 H2 O. To our surprise, the constituent (H2 C6 N7 O3 )- building block is not in structurally optimal arrangement, but Ba(H2 C6 N7 O3 )2 â 8 H2 O exhibits excellent optical properties including wide band gap of 4.10â eV, very large birefringence of 0.24@550â nm, and exceptionally strong second-harmonic generation (SHG) response of about 12×KH2 PO4 . Both the SHG response and birefringence are much larger than those of commercial NLO crystal ß-BaB2 O4 with optimally aligned (B3 O6 )3- building block. Theoretical calculations suggest that the expanded π-conjugation delocalization within (H2 C6 N7 O3 )- vs (B3 O6 )3- should be responsible to the enhanced performance. This work implies that there is still much room to develop new NLO crystals with excellent functional building blocks that may be longly neglected.
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Birefringent crystals that can switch light polarization have important applications in optoelectronics. In the last decades, birefringence is mostly optimized by chemical strategies. Recently, switching birefringence by physical means has attracted much attention. Here, this work reports the observation of heat switching birefringence in a 2D layered hybrid halide perovskite (C2 N3 H4 )2 PbCl4 ((C2 N3 H4 )+ =1,2,4-triazolium). This heat switching birefringence leads to a significant change in the interference color for the crystal plate under the illumination of orthogonal polarized light. Structure analyses reveal a heat dependent structure transition in (C2 N3 H4 )2 PbCl4 , whose birefringence is switched by the change in the distortion degree of PbCl6 octahedron. This discovery may be beneficial to the further development of stimuli-responsive polarization optical devices.
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Birefringent crystals could modulate the polarization of light and are widely used as polarizers, waveplates, optical isolators, etc. To date, commercial birefringent crystals have been exclusively limited to purely inorganic compounds such as α-BaB2 O4 with birefringence of about 0.12. Herein, we report a new hydrogen bonded supramolecular framework, namely, Cd(H2 C6 N7 O3 )2 â 8 H2 O, which exhibits exceptionally large birefringence up to about 0.60. To the best of our knowledge, the birefringence of Cd(H2 C6 N7 O3 )2 â 8 H2 O is significantly larger than those of all commercial birefringent crystals and is the largest among hydrogen bonded supramolecular framework crystals. First-principles calculations and structural analyses reveal that the exceptional birefringence is mainly ascribed to strong covalent interactions within (H2 C6 N7 O3 )- organic ligands and the perfect coplanarity between them. Given the rich structural diversity and tunability, hydrogen bonded supramolecular frameworks would offer unprecedented opportunities beyond the traditional purely inorganic oxides for birefringent crystals.
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Recent studies have provided compelling evidence linking the composition of the gut microbiota, host diet, and host physiology. Prebiotics are substrates that are selectively utilized by host microorganisms, conferring health benefits. Prebiotics, such as prebiotic blends (PB), are commonly used worldwide in food processing. Here, microbiome-metabolomics was used to evaluate how PB affect gut microbes and metabolic functions in C57BL/6 J mice administered cefixime. We found favorable effects of PB on obesity outcomes. PB supplementation significantly increased the abundance of Bifidobacterium, Parabacteroides, Alloprevotella, Alistipes, and Dubosiella, and decreased that of Robinsoniella, Blautia, Lachnoclostridium, Coprobacillus, Hungatella, Erysipelatoclostridium, Helicobacter, Clostridium sensu stricto 1, Enterococcus, and Akkermansia compared to that in the cefixime administration (CEF) group. In particular, PB increased the abundance of Parabacteroides goldsteinii and suppressed that of Robinsoniella peoriensis and Akkermansia muciniphila. In addition, it regulated the levels of microbial metabolites such as unsaturated fatty acids and bile acids. Thus, PB can alleviate metabolic disorders induced by antibiotic intervention, indicating a potential dietary strategy for populations with antibiotic-associated diarrhea. KEY POINTS: ⢠Prebiotic blends significantly increased the Parabacteroides goldsteinii colony. ⢠Prebiotic blends selectivity reversed this increase of Akkermansia muciniphila by antibiotic intervention. ⢠Prebiotic blends relieve cefixime-induced alteration of intestinal flora by regulating metabolites, such as fatty acids and bile acids.
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Microbioma Gastrointestinal , Prebióticos , Akkermansia , Animais , Antibacterianos/farmacologia , Bacteroidetes , Ácidos e Sais Biliares/farmacologia , Cefixima/farmacologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , VerrucomicrobiaRESUMO
Antiperovskites have been studied since the 1980s because of their rich physical and chemical properties, but their linear and second-order nonlinear optical responses remain largely unknown. Here we report a new polar crystal, Cs3 Cl(HC3 N3 S3 ) (I), which features a quasi-one-dimensional antiperovskite structure composed of ClCs6 polyhedra and A-site [HC3 N3 S3 ]2- rings. To our best knowledge, this kind of antiperovskite structure is reported for the first time. Remarkably, I exhibits a very strong nonlinear optical response up to 11.4 times that of the benchmark KH2 PO4 and exceptionally large birefringence of 0.52. The first-principles calculations and structural analyses reveal that [HC3 N3 S3 ]2- is the "material gene" while the antiperovskite structural feature making it in a favorable arrangement. This work provides a new structural platform for the rational design of integrated optoelectronic materials with linear and second-order nonlinear optical responses.
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Birefringent materials are highly demanded for high-performance polarized optics. As compared with artificial anisotropic metamaterials, anisotropic crystals have advantages of low optical losses and easy processing, but their birefringence is still limited. Herein, based on first-principles studies, we identified a new type of functional anion units, (Hx C6 N9 )(3-x)- (x=0, 1, 2), and then successfully synthesized a new anisotropic crystal, namely, CsH2 C6 N9 â H2 O (I), whose crystal structure consists of (H2 C6 N9 )- anions. Remarkably, I is ultraviolet transparent and exhibits very large birefringence of about 0.55@550â nm, which is much larger than those of commercial birefringent crystals. These results make I a candidate for highly efficient manipulation of optics and light in optical modulation devices. Theoretical calculations reveal that large birefringence mainly arises from the cooperative π orbitals in (H2 C6 N9 )- anions. This work provides a new insight on the underlying structure-property relationships of anisotropic crystals.
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Motivation: Genome-wide measurements of genetic and epigenetic alterations are generating more and more high-dimensional binary data. The special mathematical characteristics of binary data make the direct use of the classical principal component analysis (PCA) model to explore low-dimensional structures less obvious. Although there are several PCA alternatives for binary data in the psychometric, data analysis and machine learning literature, they are not well known to the bioinformatics community. Results: In this article, we introduce the motivation and rationale of some parametric and nonparametric versions of PCA specifically geared for binary data. Using both realistic simulations of binary data as well as mutation, CNA and methylation data of the Genomic Determinants of Sensitivity in Cancer 1000 (GDSC1000), the methods were explored for their performance with respect to finding the correct number of components, overfit, finding back the correct low-dimensional structure, variable importance, etc. The results show that if a low-dimensional structure exists in the data, that most of the methods can find it. When assuming a probabilistic generating process is underlying the data, we recommend to use the parametric logistic PCA model, while when such an assumption is not valid and the data are considered as given, the nonparametric Gifi model is recommended. Availability: The codes to reproduce the results in this article are available at the homepage of the Biosystems Data Analysis group (www.bdagroup.nl).
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Genômica/estatística & dados numéricos , Análise de Componente Principal , Algoritmos , Biologia Computacional/métodos , Biologia Computacional/estatística & dados numéricos , Simulação por Computador , Variações do Número de Cópias de DNA , Metilação de DNA , Bases de Dados Genéticas/estatística & dados numéricos , Humanos , Modelos Logísticos , Aprendizado de Máquina , Neoplasias/genética , Dinâmica não Linear , Software , Estatísticas não ParamétricasRESUMO
BACKGROUND: We evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy. METHODS: A total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response. RESULTS: Patients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001). CONCLUSIONS: Pre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/patologia , Linfócitos/patologia , Monócitos/patologia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: We conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n = 83) and in all sets. RESULTS: A high SUVmean (> 5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p < 0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9 and 92.1% in the training set, 95.8 and 97.1% in the testing set, and 92.2 and 91.8% in all sets, respectively). CONCLUSIONS: The pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.
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Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Glucose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Neutrófilos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Curva ROC , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Motivation: In biology, we are often faced with multiple datasets recorded on the same set of objects, such as multi-omics and phenotypic data of the same tumors. These datasets are typically not independent from each other. For example, methylation may influence gene expression, which may, in turn, influence drug response. Such relationships can strongly affect analyses performed on the data, as we have previously shown for the identification of biomarkers of drug response. Therefore, it is important to be able to chart the relationships between datasets. Results: We present iTOP, a methodology to infer a topology of relationships between datasets. We base this methodology on the RV coefficient, a measure of matrix correlation, which can be used to determine how much information is shared between two datasets. We extended the RV coefficient for partial matrix correlations, which allows the use of graph reconstruction algorithms, such as the PC algorithm, to infer the topologies. In addition, since multi-omics data often contain binary data (e.g. mutations), we also extended the RV coefficient for binary data. Applying iTOP to pharmacogenomics data, we found that gene expression acts as a mediator between most other datasets and drug response: only proteomics clearly shares information with drug response that is not present in gene expression. Based on this result, we used TANDEM, a method for drug response prediction, to identify which variables predictive of drug response were distinct to either gene expression or proteomics. Availability and implementation: An implementation of our methodology is available in the R package iTOP on CRAN. Additionally, an R Markdown document with code to reproduce all figures is provided as Supplementary Material. Supplementary information: Supplementary data are available at Bioinformatics online.
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Proteômica , Algoritmos , Humanos , Neoplasias/genéticaRESUMO
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with high proliferative and metastatic phenotypes. CDCA7, a new member of the cell division cycle associated family of genes, is involved in embryonic development and dysregulated in various types of human cancer. However, the biological role and molecular mechanism of CDCA7 in TNBC have not been defined. Herein, we found that CDCA7 was preferentially and markedly expressed in TNBC cell lines and tissues. High expression of CDCA7 was associated with metastatic relapse status and predicted poorer disease-free survival in patients with TNBC. We observed that CDCA7 silencing in TNBC cell lines effectively impaired cell proliferation, invasion and migration in vitro. Importantly, depletion of CDCA7 strongly reduced the tumorigenicity and distant colonization capacities of TNBC cells in vivo. Furthermore, CDCA7 increased the expression of EZH2, a marker of aggressive breast cancer that is involved in tumor progression, by enhancing the transcriptional activity of its promoter. This increase in EZH2 expression was essential for the CDCA7-mediated effects on TNBC progression. Finally, our immunohistochemical analysis revealed that the CDCA7/EZH2 axis was clinical relevant. These findings suggest CDCA7 plays a crucial role in TNBC progression by transcriptionally upregulating EZH2 and might be a potential prognostic factor and therapeutic target in TNBC.
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Proteína Potenciadora do Homólogo 2 de Zeste/biossíntese , Proteínas Nucleares/biossíntese , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Linhagem Celular Tumoral , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Nucleares/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Regulação para CimaRESUMO
Cervical cancer is the fourth most commonly occurring malignancy in females worldwide. Accumulated studies have demonstrated that the aberrant expression of microRNAs plays important roles in tumorigenesis and tumor development and potentially serves as therapeutic targets in various cancers including cervical cancer. Therefore, the identification of specific microRNAs contributed to cervical cancer formation and progression would provide critical clues for the treatments for patients with this disease. In this study, we aimed to detect microRNA-337 expression pattern and investigate the biological roles of microRNA-337 in the regulation of the malignant phenotypes of cervical cancer and its underlying mechanisms. We found that microRNA-337 expression was significantly downregulated in cervical cancer tissues and cell lines. In addition, its aberrant expression levels were positively correlated with tumor size, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis of cervical cancer. The ectopic expression of microRNA-337 suppressed cell proliferation and invasion of cervical cancer in vitro. Furthermore, specificity protein 1 was identified as a direct target of microRNA-337 in cervical cancer. The expression of specificity protein 1 increased in cervical cancer tissues and negatively correlated with microRNA-337 expression level. Moreover, rescue experiments revealed that upregulation of specificity protein 1 could rescue the effects of microRNA-337 on cervical cancer cells. Taken together, these findings collectively demonstrate that microRNA-337 exerts its tumor-suppressing roles in cervical cancer by directly targeting specificity protein 1, thereby indicating a potential novel potential therapeutic target for patients with cervical cancer.
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Proliferação de Células/genética , MicroRNAs/genética , Fator de Transcrição Sp1/biossíntese , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias do Colo do Útero/patologiaRESUMO
Prostaglandin E2 receptor 4 (EP4) is one of the receptors for prostaglandin E2 and plays important roles in various biological functions. EP4 antagonists have been used as anti-inflammatory drugs. To investigate the effects of an EP4 antagonist (L-161982) on the endogenous metabolism in a holistic manner, we employed a mouse model, and obtained metabolic and transcriptomic profiles of multiple biological matrixes, including serum, liver, and urine of mice with and without EP4 antagonist (L-161982) exposure. We found that this EP4 antagonist caused significant changes in fatty acid metabolism, choline metabolism, and nucleotide metabolism. EP4 antagonist exposure also induced oxidative stress to mice. Our research is the first of its kind to report information on the alteration of metabolism associated with an EP4 antagonist. This information could further our understanding of current and new biological functions of EP4.
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Fígado/efeitos dos fármacos , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Tiofenos/farmacologia , Triazóis/farmacologia , Animais , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs.
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Portadores de Fármacos/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Antioxidantes/metabolismo , Doxorrubicina/administração & dosagem , Doxorrubicina/toxicidade , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Nanocápsulas/toxicidade , Paclitaxel/administração & dosagem , Paclitaxel/toxicidade , Poliésteres/toxicidade , Polietilenoglicóis/toxicidadeRESUMO
Nicotinic acetylcholine receptors are important regulators of smoking behavior and tobacco carcinogenesis. We studied the association of the CHRNB3-A6 variant rs13280604 in relation to esophageal squamous cell carcinoma (ESCC) in Chinese populations. Two independent case-control studies were conducted. The first case-control study, consisted of 866 ESCC patients and 1621 healthy controls from Northern China, and the second case-control study consisted of 853 ESCC patients and 860 unrelated controls from Southern China. A logistic regression model was used to evaluate the associations of rs13280604 with cancer risk. We found that Rs13280604 GG/AG genotypes were significantly associated with increased risk for ESCC in both case-control studies from Northern [odds ratio (OR), 1.42, 95% confidence interval (CI), 1.19-1.70, P = 1.1×10(-4)], Southern China (OR, 1.56, 95% CI, 1.26-1.93, P = 5.2×10(-5)), and the combined population of both studies (OR, 1.44, 95% CI, 1.26-1.65, P = 8.7×10(-8)), respectively. Our results suggest that this CHRNB3-A6 variant confers susceptibility to ESCC risk. However, future larger studies are needed to validate our finding.
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Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Nicotínicos/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Fatores de RiscoRESUMO
PURPOSE: To evaluate the use of the buccal fat pad (BFP) in the immediate reconstruction of oncologic palate defects and the influence of postoperative radiotherapy on reconstruction. PATIENTS AND METHODS: Patients who were diagnosed with moderate- to high-grade malignancies of the palate underwent partial maxillectomy. The BFP was used as a pedicled flap to reconstruct the defects. All patients received postoperative radiotherapy 4 to 5 weeks after surgery. RESULTS: Eighteen patients (9 men and 9 women; age range, 37 to 81 yr) underwent surgery and subsequent radiotherapy. The size of all defects ranged from 7.5 to 19.2 cm2. Adequate closure of the defects was achieved during surgery and all flaps were epithelialized within 3 weeks after surgery, with no complications of dehiscence or flap failure. Furthermore, there were no complications derived from postoperative radiotherapy. CONCLUSIONS: This study suggests that BFP grafting is an effective and reliable method for the reconstruction of small to medium-size palate defects. Furthermore, postoperative radiotherapy does not influence the success of reconstruction.