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BACKGROUND: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. RESULT: A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis. CONCLUSION: The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.
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Cell adhesion and differentiation can be regulated through material engineering, but current methods have low temporal and spatial accuracy to control invivo. Here, we developed an up-conversion nanoparticle (UCNP) substrate to regulate cell adhesion and multidifferentiation in mesenchymal stem cells (MSCs) by near-infrared (NIR) light. First, the cell-adhesive peptide Arg-Gly-Asp (RGD) was conjugated on the surface of UCNPs, and the photocleavage 4-(hydroxymethyl)-3-nitrobenzoic acid (ONA) was connected to RGD. Then, the photoactivated UCNPs were linked to cover glass to form UCNP-substrate. Under the NIR, the up-convert UV from UCNPs triggered the release of ONA and exposed RGD to change the cell-matrix interactions dynamically for cell adhesion and spreading. Moreover, MSCs cultured on UCNP-substrate could be specifically induced to multidifferentiate adipocytes or osteoblasts via different power and periods of NIR irradiation in vitro and in vivo. Our work demonstrates a new way to control cell adhesion and multidifferentiation by light for regeneration medicine.
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Adesivos , Células-Tronco Mesenquimais , Adesivos/metabolismo , Adesão Celular , Oligopeptídeos/farmacologia , Peptídeos/metabolismo , Peptídeos/farmacologiaRESUMO
The functions of long noncoding (lnc)RNAs, such as MEG3, are defined by their interactions with other RNAs and proteins. These interactions, in turn, are shaped by their subcellular localization and temporal context. Therefore, it is important to be able to analyze the relationships of lncRNAs while preserving cellular architecture. The ability of MEG3 to suppress cell proliferation led to its recognition as a tumor suppressor. MEG3 has been proposed to activate p53 by disrupting the interaction of p53 with mouse double minute 2 homolog (Mdm2). To test this mechanism in the native cellular context, we employed two-color direct stochastic optical reconstruction microscopy, a single-molecule localization microscopy technique, to detect and quantify the localizations of p53, Mdm2, and MEG3 in U2OS cells. We developed a new cross-nearest neighbor/Monte Carlo algorithm to quantify the association of these molecules. Proof of concept for our method was obtained by examining the association between FKBP1A and mTOR, MEG3 and p53, and Mdm2 and p53. In contrast to previous models, our data support a model in which MEG3 modulates p53 independently of the interaction with Mdm2.
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Algoritmos , Método de Monte Carlo , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Longo não Codificante/metabolismo , Imagem Individual de Molécula/métodos , Proteína Supressora de Tumor p53/metabolismo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Proteínas Proto-Oncogênicas c-mdm2/genética , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. RESULTS: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. CONCLUSIONS: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.
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Cobre , Corantes Fluorescentes , Nanopartículas , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de OxigênioRESUMO
CircRNAs (circular RNA) are reported to regulate onset and progress multiple cancers. Nonetheless, the function along with the underlying mechanisms of circRNAs in HER-2-positive breast cancer (BC) remains unclear. CircRNA microarrays were performed to elucidate expression profiles of HER-2-positive BC cells. circRNA levels were quantified using qRT-PCR assay. Various in vitro along with in vivo assays were employed to further explore the effects of circGFRA1 in the progress of HER-2-positive BC and interactions of circGFRA1, miR-1228 and AIFM2 in Her-2-positive BC. CircGFRA1 was remarkably upregulated in HER-2-positive BC. Knockdown of circGFRA1 could attenuate HER-2-positive BC progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. In summary, circGFRA1-miR-1228-AIFM2 axis regulates HER-2-positive BC. CircGFRA1 is a novel promising treatment option for HER-2-positive BC.
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Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , MicroRNAs/genética , Proteínas Mitocondriais/genética , RNA Circular/genética , Receptor ErbB-2/genética , Animais , Apoptose/genética , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Ferroptose , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos , Interferência de RNA , Receptor ErbB-2/metabolismoRESUMO
Fourier ptychographic microscopy (FPM), as an emerging computational imaging method, has been applied to quantitative phase imaging with resolution bypassing the physical limit of the detection objective. Due to the weak illumination intensity and long image acquisition time, the achieved imaging speed in current FPM methods is still low, making them unsuitable for real-time imaging applications. We propose and demonstrate a high-speed FPM method based on using laser illumination and digital micro-mirror devices for illumination angle scanning. In this new, to the best of our knowledge, FPM method, we realized quantitative phase imaging and intensity imaging at over 42 frames per second (fps) with around 1 µm lateral resolution. The quantitative phase images have revealed membrane height fluctuations of red blood cells with nanometer-scale sensitivity, while the intensity images have resolved subcellular features in stained cancer tissue slices.
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Algoritmos , Microscopia , Análise de Fourier , Luz , IluminaçãoRESUMO
BACKGROUND: Metastasis accounts for the majority of deaths in patients with breast cancer. Liver metastasis is reported common for breast cancer patients. The purpose of this study was to construct a nomogram to predict the likelihood of subsequent liver metastasis in patients with nonmetastatic breast cancer, thus high-risk patient populations can be prevented and monitored. METHODS: A total of 1840 patients with stage I-III breast cancer were retrospectively included and analyzed. A nomogram was constructed to predict liver metastasis based on multivariate logistic regression analysis. SEER database was used for external validation. C-index, calibration curve and decision curve analysis were used to evaluate the predictive performance of the model. RESULTS: The nomogram included 3 variables related to liver metastasis: HER2 status (odds ratio (OR) 1.86, 95%CI 1.02 to 3.41; P = 0.045), tumor size (OR 3.62, 1.91 to 6.87; P < 0.001) and lymph node metastasis (OR 2.26, 1.18 to 4.34; P = 0.014). The C index of the training cohort, internal validation cohort and external validation cohort were 0.699, 0.814 and 0.791, respectively. The nomogram was well-calibrated, with no statistical difference between the predicted and the observed probabilities. CONCLUSION: We have developed and validated a robust tool enabled to predict subsequent liver metastasis in patients with nonmetastatic breast cancer. Distinguishing a population of patients at high risk of liver metastasis will facilitate preventive treatment or monitoring of liver metastasis.
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Neoplasias da Mama/complicações , Neoplasias Hepáticas/secundário , Mastectomia/efeitos adversos , Nomogramas , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Estadiamento de NeoplasiasRESUMO
The circular RNA, CDR1as/ciRS-7, functions as a vital regulator in various cancers; however, the predictive value of CDR1as remains controversial. Therefore, a comprehensive analysis for clarifying the precise diagnostic and prognostic value of CDR1as in solid tumours is needed. A literature review of several databases was conducted for identifying potential studies. Pooled odds ratios (ORs) and hazard ratios (HRs) were used for evaluating the diagnostic accuracy variables and survival. Overall, 15 studies (1787 patients) and 11 studies (1578 patients) were included for diagnostic and prognostic outcome syntheses, respectively. Up-regulated CDR1as expression was found to be correlated with worse clinicopathological characteristics, including the T status, N status, histological grade, TNM stage and distant metastasis. The synthesized sensitivity was 0.72 (95% confidence interval [CI], 0.65-0.79), and the specificity was 0.80 (95% CI, 0.74-0.86). The positive likelihood ratio (LR), negative LR and diagnostic odds ratio (DOR) were 3.70, 0.34 and 10.80, respectively. The area under the receiver operator characteristic curve was 0.84 (95% CI, 0.80-0.87). In the pooled prognostic analysis, patients with high CDR1as expression had worse overall survival (HR = 2.40, P < 0.001) and disease-free survival (HR = 1.74, P < 0.001). These results suggest that CDR1as is a reliable diagnostic and prognostic biomarker with high accuracy and efficiency, which may potentially facilitate clinical decisions on solid tumours in the future.
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Neoplasias/genética , Neoplasias/patologia , RNA Circular/genética , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Humanos , Prognóstico , Curva ROCRESUMO
The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs), intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (Meg3-DMR). In mice, a maternal deletion of the IG-DMR leads to LOI in the locus, proving that the IG-DMR is a cis-acting imprinting control region of the locus. However, the Meg3-DMR overlaps with the promoter, exon 1 and intron 1 of the Meg3 gene. Because deletion of the Meg3-DMR inactivates the Meg3 gene, their roles in imprinting regulation of Meg3-DMR mice is unknown. Therefore, we generated two mouse models: Meg3Δ(1-4) and Meg3Δ(2-4), respectively targeting exons 1-4 and exons 2-4 of the Meg3 gene. A maternal deletion of Meg3Δ(1-4) caused embryonic death and LOI in both embryos and placentas, but did not affect methylation status of the IG-DMR. In contrast, mice carrying a maternal deletion of Meg3Δ(2-4) were born normally and did not have LOI. These data indicate that it is the Meg3-DMR, not the Meg3 gene, which regulates imprinting of the Dlk1-Dio3 locus.
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Metilação de DNA , Loci Gênicos , Impressão Genômica , RNA Longo não Codificante/genética , Animais , Proteínas de Ligação ao Cálcio/genética , Desenvolvimento Embrionário/genética , Éxons/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Iodeto Peroxidase/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Camundongos Transgênicos , Placenta/metabolismo , Gravidez , Deleção de SequênciaRESUMO
Our study aims to construct a prognosis-related immune phenotype classifier for predicting clinical prognosis and immune activity in triple-negative breast cancer (TNBC). A total of 237 patients with TNBC from Sun Yat-sen University Cancer Center (SYSUCC) and 533 patients with TNBC from public datasets were included in our study. A stromal immune quantified index was generated with a LASSO Cox regression model based on five prognosis-related immune cells evaluated by CIBERSORT or IHC and was used to determine immune phenotypes. Immune features were evaluated in the samples before chemotherapy. A total of 119 patients in the SYSUCC training cohort were classified into immune Phenotypes A and B according to the density of stromal CD4+ T cells, γδ T cells, monocytes, M1 macrophages and M2 macrophages. Phenotype A predicted better survival than Phenotype B, and the classification was further validated in the testing cohort of 118 patients and the validation cohort of 533 patients. In the combined cohort, significant differences were found in Phenotype A compared to Phenotype B for the 5-year overall survival (83.5% vs 65.8%, respectively, P < .01) and the 5-year disease-free survival (87.3% vs 76.0%, respectively, P < .01). In Phenotype A, immune-related pathways were significantly enriched, and a higher level of immune checkpoint molecules, including PD-L1, PD-1 and CTLA-4, could be observed. The immune phenotype classification was an independent prognostic indicator for TNBC and might serve as a potential predictor for immune activity within the tumor microenvironment.
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Biomarcadores Tumorais/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos Intraepiteliais/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Neoplasias de Mama Triplo Negativas/imunologia , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fenótipo , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Análise de Regressão , Análise de Sobrevida , Microambiente Tumoral , Regulação para CimaRESUMO
BACKGROUND Our study aims to investigate the role of segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) in the monitoring of upper limb water changes of patients with breast cancer before and after surgery to aid in establishing a new approach to preventing lymphedema. MATERIAL AND METHODS This study included 442 female patients with breast cancer. We used SMF-BIA to monitor changes in body composition. Data were collected 1 day before surgery and 7 days and 3 months after surgery. RESULTS The average body mass index (BMI) of patients was normal but, in 22.8% of patients, the percentage of body fat exceeded the average, which is known as invisible obesity. Moreover, the weight, BMI, basal metabolic rate, inorganic salt content, muscle content, total body water, and extracellular water of patients increased 7 days after surgery (P<0.05), but recovered to preoperative levels within 3 months. In addition, protein content, skeletal muscle content, and intracellular water increased 7 days after surgery, but decreased within 3 months to even lower levels than before surgery (P<0.05). The extracellular water and total body water ratios increased continuously within the 3 months after surgery. Finally, the segmental water ratio of the healthy and affected upper limbs increased, while the bioelectrical impedance value decreased; however, they were still within the normal range. CONCLUSIONS SMF-BIA monitoring may provide more detailed information for making individual nursing care plans in patients with breast cancer. Further studies with long-term follow-up are urgently needed to establishment a lymphedema risk predictive model.
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Adiposidade , Água Corporal , Linfedema Relacionado a Câncer de Mama/diagnóstico , Neoplasias da Mama/patologia , Impedância Elétrica , Adulto , Idoso , Índice de Massa Corporal , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Extremidade Superior/patologiaRESUMO
As a new rising star of non-coding RNA, circular RNAs (circRNAs) emerged as vital regulators with biological functions in diverse of cancers. However, the function and precise mechanism of the vast majority of circRNAs in triple-negative breast cancer (TNBC) occurrence and progression have not been clearly elucidated. In the current study, we identified and further investigated hsa_circ_0002453 (circRAD18) by analyzing our previous microarray profiling. Expression of circRAD18 was found significantly upregulated in TNBC compared with normal mammary tissues and cell lines. circRAD18 was positively correlated with T stage, clinical stage and pathological grade and was an independent risk factor for TNBC patients. We performed proliferation, colony formation, cell migration, apoptosis and mouse xenograft assays to verify the functions of circRAD18. Knockdown of circRAD18 significantly suppressed cell proliferation and migration, promoted cell apoptosis and inhibited tumor growth in functional and xenograft experiments. Through luciferase reporter assays, we confirmed that circRAD18 acts as a sponge of miR-208a and miR-3164 and promotes TNBC progression through upregulating IGF1 and FGF2 expression. Altogether, our research revealed the pivotal role of circRAD18-miR-208a/3164-IGF1/FGF2 axis in TNBC tumorigenesis and metastasis though the mechanism of competing endogenous RNAs. Thus, circRAD18 may serve as a novel prognostic biomarker and potential target for TNBC treatment in the future.
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Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , RNA Circular/genética , Neoplasias de Mama Triplo Negativas/genética , Ubiquitina-Proteína Ligases/genética , Animais , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Fator 2 de Crescimento de Fibroblastos/biossíntese , Xenoenxertos , Humanos , Fator de Crescimento Insulin-Like I/biossíntese , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
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Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de SobrevidaRESUMO
To unveil the origin of the hydrogen-storage properties of rhodium nanoparticles (Rh NPs), we investigated the electronic and crystal structures of the Rh NPs using various synchrotron based X-ray techniques. Electronic structure studies revealed that the hydrogen-storage capability of Rh NPs could be attributed to their more unoccupied d-DOSs than that of the bulk near the Fermi level. Crystal structure studies indicated that lattice distortion and mean-square displacement increase while coordination number decreases with decreasing particle size and the hydrogen-absorption capability of Rh NPs improves to a greater extent with increased structural disorder in the local structure than with that in the mean structure. The smallest Rh NPs, having the largest structural disorder/increased vacancy spaces and the smallest coordination number, exhibited excellent hydrogen-storage capacity. Finally, from the bond-orientational order analysis, we confirmed that the localized disordering is distributed more over the surface part than the core part and hydrogen can be trapped on the surface part of Rh NPs which increases with a decrease in NP diameter.
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BACKGROUND The present organ shortage has led to increased use of kidneys from expanded-criteria donors, but the prognosis is disappointing due to poor graft quality. As a promising kidney protector, the Klotho gene's role in predicting short-term prognosis has not been assessed. MATERIAL AND METHODS We retrospectively analyzed data from 41 recipients and 25 donors. Multiple clinical variables were compared between different subgroups of donors or their corresponding recipients. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the distinguishing ability. Dynamic changes in serum Klotho, FGF-23, and urinary NGAL were assessed. RESULTS Serum Klotho level was significantly lower in donors age ≥50 years (p=0.017), and there was a moderate negative correlation between serum Klotho expression and age (r=-0.464, p=0.019). Moreover, detection of Klotho mRNA and immunohistochemical analysis in kidneys revealed the same trend as in serum. Furthermore, for older donors (age ≥50 years), serum Klotho level had a strong negative correlation with recipient eGFR 1 month post-transplant (r=-0.686, p=0.007), which was proved to be a good predictor for estimating graft function by ROC analysis. Additionally, during the post-transplant follow-up, serum Klotho levels increased slightly after a temporary decline, while serum FGF-23 and urinary NGAL decreased significantly and then stayed low thereafter. CONCLUSIONS Klotho level, which decreases with age, may be a potential predictor of short-term renal function, especially for grafts from older donors.
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Glucuronidase/genética , Glucuronidase/metabolismo , Adulto , Fatores Etários , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Glucuronidase/sangue , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Transplante de Rim/métodos , Proteínas Klotho , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Doadores de TecidosRESUMO
Notwithstanding compelling contribution of NF-κB to the progression of osteoporosis has been reported, little is known regarding direct inhibition of NF-κB benefiting osteoporosis. In this study, therefore, we evaluated the role of celastrol, an NF-κB inhibitor, in a mouse model of secondary osteoporosis. Animals were divided into three groups as Sham (control), SO (secondary osteoporosis) and SO + CA (secondary osteoporosis treated with celastrol). Significant decreases in body weight and body fat were observed following celastrol treatment in SO group, but leptin levels were much higher. Celastrol also exhibited a significant decrease in urinary calcium excretion. Moreover, other important events were observed after celastrol treatment, covering substantial decrements in serum concentrations of PTH, TRAP-5b, CTX and DPD, improved structure of articular cartilage and cancellous bone (revealed by H&E and safranin-O staining), and significant decline in levels of NF-κB (P65), MMP-1, and MMP-9. These findings demonstrated that celastrol treatment not only improved abnormal lipid metabolism and hypercalciuria in mice subjected to secondary osteoporosis, but also ameliorated articular cartilage lesions. Our results provided evidence of targeted therapy for NF-κB in the clinical treatment of secondary osteoporosis.
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Cartilagem Articular , Hipercalciúria/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , NF-kappa B/fisiologia , Osteoporose/tratamento farmacológico , Osteoporose/genética , Triterpenos/farmacologia , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Leptina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular , Hormônio Paratireóideo/sangue , Triterpenos Pentacíclicos , Triterpenos/uso terapêuticoRESUMO
The 3-dimensional (3D) atomic-scale structure of newly discovered face-centered cubic (fcc) and conventional hexagonal close packed (hcp) type ruthenium (Ru) nanoparticles (NPs) of 2.2 to 5.4 nm diameter were studied using X-ray pair distribution function (PDF) analysis and reverse Monte Carlo (RMC) modeling. Atomic PDF based high-energy X-ray diffraction measurements show highly diffuse X-ray diffraction patterns for fcc- and hcp-type Ru NPs. We here report the atomic-scale structure of Ru NPs in terms of the total structure factor and Fourier-transformed PDF. It is found that the respective NPs have substantial structural disorder over short- to medium-range order atomic distances from the PDF analysis. The first-nearest-neighbor peak analyses show a significant size dependence for the fcc-type Ru NPs demonstrating the increase in the peak height due to an increase in the number density as a function of particle size. The bond angle and coordination number (CN) distribution for the RMC-simulated fcc- and hcp-type Ru NP models indicated inherited structural features from their bulk counterparts. The CN analysis of the whole NP and surface of each RMC model of Ru NPs show the low activation energy packing sites on the fcc-type Ru NP surface atoms. Finally, our newly defined order parameters for RMC simulated Ru NP models suggested that the enhancement of the CO oxidation activity of fcc-type NPs was due to a decrease in the close packing ordering that resulted from the increased NP size. These structural findings could be positively supported for synthesized low-cost and high performance nano-sized catalysts and have potential application in fuel-cell systems and organic synthesis.
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MicroRNAs (miRNAs) are small non-protein-codingRNAs that function as negative gene expression regulators. miRNA-210 (miR-210) has recently been recognized in the pathogenesis of osteonecrosis associated with angiogenesis. Herein we aimed to explore the clinical significance of miR-210 treatment for postmenopausal osteoporosis. The expression of miR-210 was detected in bone marrow mesenchymal stem cells (BMSCs) in vitro and miR-210 significantly promoted the expression of vascular edothelial growth factor (VEGF) in BMSCs in a time-dependent manner (p<0.05). And miR-210 suppressed PPARγ expression but increased the expression of ALP and osterix, demonstrating that miR-210 inhibited adipocyte differentiation and promoted osteoblast differentiation of BMSCs in vitro. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and VEGF in 17ß-estradiol (E2) treated osteoblasts were significantly increased in a dose- and time-dependent manner (p<0.05). And E2 inducted the VEGF expression through the PI3K/AKT signaling pathway in osteoblasts. Taken together, these data implied that miR-210 played an important role in ameliorating the estrogen deficiency caused-postmenopausal osteoporosis through promotion the VEGF expression and osteoblast differentiation.
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MicroRNAs/metabolismo , Osteoblastos/citologia , Osteoporose Pós-Menopausa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Estrogênios/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteogênese , Osteoporose Pós-Menopausa/genética , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
The core-level and valence-band electronic structures of LixNi1-xO epitaxial thin films with x = 0, 0.27, and 0.48 were studied by hard X-ray photoelectron spectroscopy. A double peak structure, consisting of a main peak and a shoulder peak, and a satellite structure were observed in the Ni 2p3/2 core-level spectra. The intensity ratio of the shoulder to main peak in this double peak structure increased with increasing lithium content in LixNi1-xO. This lithium doping dependence of the Ni 2p3/2 core-level spectra was investigated using an extended cluster model, which included the Zhang-Rice (ZR) doublet bound states arising from a competition between O 2p - Ni 3d hybridization and the Ni on-site Coulomb interaction. The results indicated that the change in the intensity ratio in the main peak is because of a reduction in the ZR doublet bound states from lithium substitutions. This strongly suggests that holes compensating Li doping in LixNi1-xO are of primarily ZR character.