Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 142
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 629(8012): 679-687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693266

RESUMO

Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study1. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution. To elucidate genetic relationships between and within PanINs, we developed a workflow in which 3D modelling guides multi-region microdissection and targeted and whole-exome sequencing. From these samples, we calculated a mean burden of 13 PanINs per cm3 and extrapolated that the normal intact adult pancreas harbours hundreds of PanINs, almost all with oncogenic KRAS hotspot mutations. We found that most PanINs originate as independent clones with distinct somatic mutation profiles. Some spatially continuous PanINs were found to contain multiple KRAS mutations; computational and in situ analyses demonstrated that different KRAS mutations localize to distinct cell subpopulations within these neoplasms, indicating their polyclonal origins. The extensive multifocality and genetic heterogeneity of PanINs raises important questions about mechanisms that drive precancer initiation and confer differential progression risk in the human pancreas. This detailed 3D genomic mapping of molecular alterations in human PanINs provides an empirical foundation for early detection and rational interception of pancreatic cancer.


Assuntos
Heterogeneidade Genética , Genômica , Imageamento Tridimensional , Neoplasias Pancreáticas , Lesões Pré-Cancerosas , Análise de Célula Única , Adulto , Feminino , Humanos , Masculino , Células Clonais/metabolismo , Células Clonais/patologia , Sequenciamento do Exoma , Aprendizado de Máquina , Mutação , Pâncreas/anatomia & histologia , Pâncreas/citologia , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Fluxo de Trabalho , Progressão da Doença , Detecção Precoce de Câncer , Oncogenes/genética
2.
J Am Chem Soc ; 146(1): 1109-1121, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38141046

RESUMO

The energy dissipative features of hydrogen bonds under conditions of mechanical strain have provided an ongoing incentive to explore hydrogen bonding units for the purpose of controlling and customizing the mechanical properties of polymeric materials. However, there remains a need for hydrogen bond units that (1) possess directionality, (2) provide selectivity, (3) dissipate energy effectively, and (4) can be incorporated readily into polymeric materials to regulate their mechanical properties. Here, we report mechanically interlocked hydrogen bond units that incorporate multiple hydrogen bonds within a [2]catenane structure. The conformational flexibility and associated spatial folding characteristics of the [2]catenane units allow for molecular scale motion under external stress, while the interlocked structure serves as a pivot that maintains the directionality and selectivity of the resultant hydrogen bonding units. When incorporated into polymers, these interlocked hydrogen bond motifs serve to strengthen and toughen the resulting materials. This study not only presents a novel hydrogen bond unit for creating polymeric materials with improved mechanical properties but also underscores the unique opportunities that mechanically interlocked hydrogen bond structures may provide across a diverse range of applications.

3.
J Am Chem Soc ; 146(18): 12547-12555, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38656766

RESUMO

Three-dimensional (3D) crystalline organic frameworks with complex topologies, high surface area, and low densities afford a variety of application prospects. However, the design and construction of these frameworks have been largely limited to systems containing polyhedron-shaped building blocks or those relying on component interpenetration. Here, we report the synthesis of a 3D crystalline organic framework based on molecular mortise-and-tenon jointing. This new material takes advantage of tetra(4-pyridylphenyl)ethylene and chlorinated bis(benzodioxaborole)benzene as building blocks and is driven by dative B-N bonds. A single-crystal X-ray diffraction analysis of the framework reveals the presence of two-dimensional (2D) layers with helical channels that are formed presumably during the boron-nitrogen coordination process. The protrusion of dichlorobenzene units from the upper and lower surfaces of the 2D layers facilitates the key mortise-and-tenon connections. These connections enable the interlocking of adjacent layers and the stabilization of an overall 3D framework. The resulting framework is endowed with high porosity and attractive mechanical properties, rendering it potentially suitable for the removal of impurities from acetylene.

4.
Angew Chem Int Ed Engl ; 63(23): e202405761, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38587998

RESUMO

Vitrimers offer a unique combination of mechanical performance, reprocessability, and recyclability that makes them highly promising for a wide range of applications. However, achieving dynamic behavior in vitrimeric materials at their intended usage temperatures, thus combining reprocessability with adaptivity through associative dynamic covalent bonds, represents an attractive but formidable objective. Herein, we couple boron-nitrogen (B-N) dative bonds and B-O covalent bonds to generate a new class of vitrimers, boron-nitrogen vitrimers (BNVs), to endow them with dynamic features at usage temperatures. Compared with boron-ester vitrimers (BEVs) without B-N dative bonds, the BNVs with B-N dative bonds showcase enhanced mechanical performance. The excellent mechanical properties come from the synergistic effect of the dative B-N supramolecular polymer and covalent boron-ester networks. Moreover, benefiting from the associative exchange of B-O dynamic covalent bonds above their topological freezing temperature (Tv), the resultant BNVs also possess the processability. This study leveraged the structural characteristics of a boron-based vitrimer to achieve material reinforcement and toughness enhancement, simultaneously providing novel design concepts for the construction of new vitrimeric materials.

5.
Angew Chem Int Ed Engl ; 63(13): e202317947, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38298087

RESUMO

Although our knowledge and understanding of adsorptions in natural and artificial systems has increased dramatically during the past century, adsorption associated with nonporous polymers remains something of a mystery, hampering applications. Here we demonstrate a model system for adaptisorption of nonporous polymers, wherein dative B-N bonds and host-guest binding units act as the kinetic and thermodynamic components, respectively. The coupling of these two components enables nonporous polymer crystals to adsorb molecules from solution and undergo recrystallization as thermodynamically favored crystals. Adaptisorption of nonporous polymer crystals not only extends the types of adsorption in which the sorbate molecules are integrated in a precise and orderly manner in the sorbent systems, but also provides a facile and accurate approach to the construction of polymeric materials with precise architectures and integrated functions.

6.
J Proteome Res ; 22(7): 2391-2399, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37314855

RESUMO

Correctly identifying the human hair anatomic location found at crime scenes can link biological sample donors with the actual crime event, thus providing significant insight into the crime scene reconstruction. Forensic proteomic studies on human hairs can facilitate the development of new biomarkers for hair identification while compensating for the limitations of the conventional morphologic hair comparison and DNA analysis. Herein, the LC-MS/MS platform was used to find differentially expressed protein biomarkers in hairs from different body sites. The findings indicated that a total of 296 protein biomarkers with statistically significant differences in body sites were initially identified, and hair samples from the scalp, pubic, and armpit parts were distinguished from each other, which were validated by multiple bioinformatic methods. Fewer differences in protein patterns between armpit and pubic hairs while larger differences between hair and armpit as well as pubic hairs provided reasonable evidence of sexual or close intimate contact in crimes. This study lays the foundation for the development of a more reliable strategy to distinguish human hairs of various body areas from Chinese and will also support microscopic hair comparison analysis and assist in the proper handling of legal proceedings in relative cases by judicial officers, deserving special attention and further in-depth investigation. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD038173.


Assuntos
Corpo Humano , Proteômica , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Cabelo/química , Proteínas/análise , Biomarcadores
7.
Proc Natl Acad Sci U S A ; 117(48): 30488-30497, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33199631

RESUMO

Transforming growth factor-ß (TGF-ß) signaling is a critical regulator for articular cartilage tissue maintenance and chondrocyte homeostasis. Nonetheless, the regulatory networks and downstream signaling pathways that govern the chondroprotective function of TGF-ß in the context of osteoarthritis (OA) are not fully defined. Recent studies reveal that mice with postnatal deletion of triple forkhead box class Os (FoxOs) (1, 3, and 4) spontaneously develop OA-like pathologies. The OA phenotype largely recapitulates that observed in mice with loss of TGF-ßR2. In the present study, we investigated the role of FoxOs as downstream mediators of TGF-ß signaling and define their role in articular cartilage homeostasis. Among the three FoxOs (1, 3, and 4), TGF-ß signaling exclusively regulates FoxO1 in a TGF-ß activated kinase 1 (TAK1)-dependent manner. Furthermore, FoxO1 was genetically ablated in mice in a tissue-specific manner in articular cartilage or overexpressed in adult cartilage immediately followed by meniscal/ligament injury (MLI). Histological and microcomputed tomography (micro-CT) analyses demonstrated that loss of FoxO1 postnatally in articular cartilage leads to OA-like pathologies, and gain of FoxO1 in adult cartilage has both preventative and therapeutic effects on surgically induced OA. Mechanistically, FoxO1 was found to maintain articular chondrocyte homeostasis through induction of anabolic and autophagy-related gene expressions. Importantly, overexpression of FoxO1 markedly rescued the OA phenotypes caused by deficiency in TGF-ß signaling in chondrocytes. Our study identifies that TGF-ß/TAK1-FoxO1 is a key signaling cascade in regulation of articular cartilage autophagy and homeostasis and is a potentially important therapeutic target for OA-like joint diseases.


Assuntos
Cartilagem Articular/metabolismo , Proteína Forkhead Box O1/genética , MAP Quinase Quinase Quinases/metabolismo , Osteoartrite/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Animais , Autofagia , Biomarcadores , Cartilagem Articular/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Proteína Forkhead Box O1/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Homeostase , Camundongos , Camundongos Knockout , Modelos Biológicos , Osteoartrite/etiologia , Osteoartrite/patologia , Espécies Reativas de Oxigênio/metabolismo , Microtomografia por Raio-X
8.
Nonlinear Dyn ; 111(11): 10677-10692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152860

RESUMO

In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.

9.
J Minim Access Surg ; 19(4): 540-543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37861647

RESUMO

Introduction: The objective of this study was to investigate the diagnostic value of endoscopic ultrasonography (EUS) for tumours around the duodenal ampullary. Patients and Methods: A retrospective analysis was performed on cases diagnosed and treated in our hospital from October 2016 to August 2021 due to the lesions around the duodenal ampulla. All patients received EUS, abdominal enhanced computed tomography (CT) and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography (MRI-MRCP). Pathological diagnosis was used to verify the accuracy of the imaging findings. The detection rates of periampullary tumours by EUS, abdominal enhanced CT and MRI-MRCP were determined and compared. Results: A total of 86 patients were included in this study. According to the pathological diagnosis, the detection rate of EUS was 87% (36/41) for periampullary tumour lesions with a tumour diameter <1 cm, which was significantly higher than that of MRI-MRCP (59%, 24/41) (P = 0.003) and CT (44%, 18/41) (P < 0.001). For periampullary tumour lesions with a tumour diameter ≥1 cm, the detection rate of MRI-MRCP was 93% (42/45), which was significantly higher than that of EUS (78%, 35/45) (P = 0.036) and CT (76%, 34/45) (P = 0.02). Conclusions: EUS can accurately detect tumour lesions around the ampullary part of the duodenum with minimal gas interference. For periampullary tumour lesions <1 cm, EUS has better diagnostic accuracy than abdominal-enhanced CT and MRI-MRCP. In addition, a biopsy of the lesion can be performed at the same time during the EUS examination. Therefore, EUS has an important clinical significance and value in the diagnosis of duodenal periampullary tumours.

10.
Eur Arch Otorhinolaryngol ; 279(3): 1489-1498, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34152476

RESUMO

OBJECTIVES: To describe the clinicopathological characteristics and determinants of survival of patients with mucoepidermoid carcinoma (MEC) of the tongue. METHOD: Retrospective population-based study was conducted using the data of patients diagnosed with MEC of the tongue from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. RESULTS: A total of 200 cases of MEC of the tongue were identified. The cohort was composed of 56.5% females. The mean age at diagnosis was 58.8 years. The base of the tongue was the most common primary site (72.5%). Most cases (80.9%) presented with T1 and T2. Lymph node metastases was present in 40.9% of cases, while distant metastases only observed in 2.2% of cases. Overall survival (OS) at 2, 5, and 10 years was 80.2%, 69.8%, and 52.4%, respectively. 77.5 percent of cases (155/200) underwent surgery, and 66 cases received both surgery and radiation therapy. Patients with post-operative radiation had much longer disease-specific survival (DSS). Advanced T stage, distant metastasis contributed independently to shorter OS, while the use of surgery is an independently favorable prognostic factor for OS. In addition, an OS-specific nomogram was established, and the C-index for OS prediction was 0.74 (95% CI 0.67-0.81). CONCLUSION: This rare malignancy is associated with a generally favorable prognosis, and T stage, distant metastasis as well as surgical therapy are independent predictors of OS.


Assuntos
Carcinoma Mucoepidermoide , Carcinoma Mucoepidermoide/epidemiologia , Carcinoma Mucoepidermoide/patologia , Feminino , Humanos , Masculino , Nomogramas , Prognóstico , Estudos Retrospectivos , Programa de SEER , Língua/patologia
11.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3402-3408, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851136

RESUMO

Chinese medicine pharmaceutical industry is in the process of digital and intelligent transformation. Intelligent methods are required for efficient analysis and mining of the valuable information in the history data including literature data, pharmaceutical big data, and expert knowledge. Therefore, it is urgent to establish a knowledge-driven intelligent system of pharmaceutical technologies of Chinese medicine for efficient supplying of high-quality Chinese medicinal products. The present study proposed the construction method of the knowledge base of Chinese medicine manufacturing, which was preliminarily established from literature mining, case-based reasoning, and real-time prediction based on vacuum belt drying process optimization. Integrating the technologies(such as deep learning, case-based reasoning, and simulation modeling), pharmaceutical mechanisms, and big data, the knowledge base of Chinese medicine manufacturing can realize knowledge automation and scientific decision-making. It provides an example for upgrading from experience-based manufacturing to intelligent Chinese medicine manufacturing.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Bases de Conhecimento , Controle de Qualidade , Tecnologia Farmacêutica
12.
Br J Nutr ; 123(5): 481-488, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31623699

RESUMO

The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isoenergetic diets formulated with glucose, soya oil or glutamine for 28 d. On day 14 or 28, the proteins in crypt enterocytes were analysed with isobaric tags for relative and absolute quantification and proteins involved in mTORC1 signalling pathway in villus or crypt compartment cells were determined by Western blotting. Our results showed no significant differences (P > 0·05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of eukaryotic initiation factor-4E binding protein-1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soya oil. On day 28, higher protein expression of phosphor-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soya oil. In conclusion, the isoenergetic glucose, soya oil or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared with soya oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.


Assuntos
Suplementos Nutricionais , Glucose/farmacologia , Glutamina/farmacologia , Óleo de Soja/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Enterócitos/metabolismo , Jejuno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Suínos , Desmame
13.
Anticancer Drugs ; 30(10): 998-1005, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31625993

RESUMO

We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Fator Regulador 3 de Interferon/metabolismo , Proantocianidinas/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fator Regulador 3 de Interferon/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Proteínas Proto-Oncogênicas c-jun/genética
15.
Electrophoresis ; 38(8): 1154-1162, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28168762

RESUMO

Nonbinary single-nucleotide polymorphisms (SNPs) are potential forensic genetic markers because their discrimination power is greater than that of normal binary SNPs, and that they can detect highly degraded samples. We previously developed a nonbinary SNP multiplex typing assay. In this study, we selected additional 20 nonbinary SNPs from the NCBI SNP database and verified them through pyrosequencing. These 20 nonbinary SNPs were analyzed using the fluorescent-labeled SNaPshot multiplex SNP typing method. The allele frequencies and genetic parameters of these 20 nonbinary SNPs were determined among 314 unrelated individuals from Han populations from China. The total power of discrimination was 0.9999999999994, and the cumulative probability of exclusion was 0.9986. Moreover, the result of the combination of this 20 nonbinary SNP assay with the 20 nonbinary SNP assay we previously developed demonstrated that the cumulative probability of exclusion of the 40 nonbinary SNPs was 0.999991 and that no significant linkage disequilibrium was observed in all 40 nonbinary SNPs. Thus, we concluded that this new system consisting of new 20 nonbinary SNPs could provide highly informative polymorphic data which would be further used in forensic application and would serve as a potentially valuable supplement to forensic DNA analysis.


Assuntos
Fluorescência , Ciências Forenses/métodos , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Animais , China , Eletroforese/métodos , Frequência do Gene , Marcadores Genéticos , Genética Populacional , Humanos , Desequilíbrio de Ligação , Sensibilidade e Especificidade
16.
Cell Mol Life Sci ; 73(20): 3917-33, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27113546

RESUMO

Vascular permeability regulated by the vascular endothelial growth factor (VEGF) through endothelial-barrier junctions is essential for inflammation. Mechanisms regulating vascular permeability remain elusive. Although 'Akt' and 'Src' have been implicated in the endothelial-barrier regulation, it is puzzling how both agents that protect and disrupt the endothelial-barrier activate these kinases to reciprocally regulate vascular permeability. To delineate the role of Akt1 in endothelial-barrier regulation, we created endothelial-specific, tamoxifen-inducible Akt1 knockout mice and stable ShRNA-mediated Akt1 knockdown in human microvascular endothelial cells. Akt1 loss leads to decreased basal and angiopoietin1-induced endothelial-barrier resistance, and enhanced VEGF-induced endothelial-barrier breakdown. Endothelial Akt1 deficiency resulted in enhanced VEGF-induced vascular leakage in mice ears, which was rescued upon re-expression with Adeno-myrAkt1. Furthermore, co-treatment with angiopoietin1 reversed VEGF-induced vascular leakage in an Akt1-dependent manner. Mechanistically, our study revealed that while VEGF-induced short-term vascular permeability is independent of Akt1, its recovery is reliant on Akt1 and FoxO-mediated claudin expression. Pharmacological inhibition of FoxO transcription factors rescued the defective endothelial barrier due to Akt1 deficiency. Here we provide novel insights on the endothelial-barrier protective role of VEGF in the long term and the importance of Akt1-FoxO signaling on tight-junction stabilization and prevention of vascular leakage through claudin expression.


Assuntos
Células Endoteliais/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Junções Íntimas/metabolismo , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/metabolismo , Angiopoietina-1/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Claudina-5/metabolismo , Células Endoteliais/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Camundongos Transgênicos , Microvasos/citologia , Proteínas Proto-Oncogênicas c-akt/deficiência , Junções Íntimas/efeitos dos fármacos , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/farmacologia
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 295-298, 2017 Mar.
Artigo em Zh | MEDLINE | ID: mdl-28612546

RESUMO

OBJECTIVES: To synthesize 3'-deoxy-3'-¹8F-fluorotyhymidine)(¹8F-FLT) using CFN-MPS-200 automatic synthesis module, and evaluate its distribution in Wistar rats. METHODS: We used 3-N-Boc-5!d-O-dimethoxytrityl-3!d-O-nosyl-thymidine (Boc-FLT)-percursor as raw material to synthesize ¹8F-FLT without residual solvents. Its radiochemical purity was confirmed with radio-HPLC and thin layer chromatography (TLC). Normal Wistar rats were injected with 18 F-FLT and underwent PET scanning. RESULTS: The entire preparation procedure took about 60 min, which resulted in a radio chemical yield of (24±5)% (after attenuation correction, n =20) and radiochemical purity of over 99%, with 1.11×108 Bq/mL specific activity. The ¹8F-FLT solution was colorless and had a pH value between 7.0-8.0. ¹8F-FLT was mainly concentrated in the kidney, bladder, liver, bone marrow and Liver of normal Wistar rats. CONCLUSION: Automated synthesis of ¹8F-FLT using CFN-MPS-200 is a stable method, with high yield, safety without solvent, and acceptable quality.


Assuntos
Didesoxinucleosídeos/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Tomografia por Emissão de Pósitrons , Controle de Qualidade , Ratos , Ratos Wistar
18.
EMBO J ; 31(5): 1134-46, 2012 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22307088

RESUMO

The requirement of Akt for cell proliferation and oncogenesis is mammalian target of rapamycin complex 1 (mTORC1) dependent. SV40 large T expression in Akt-deficient cells restores cell proliferation rate, but is insufficient for exiting contact inhibition and oncogene-induced anchorage-independent growth, because of a failure to promote Skp2 mRNA translation. Skp2 mRNA and protein are induced upon exiting contact inhibition, which enables entry into mitosis. While Skp2 mRNA is induced in Akt-deficient cells, it is not translated, preventing entry into mitosis. Restoring Skp2 expression in Akt-deficient cells is sufficient to restore exit from contact inhibition and oncogenesis. Skp2 mRNA translation is dependent on mTORC1 and the eukaryotic translation initiation factor 4E (eIF4E). Thus, the requirement of Akt for exiting contact inhibition is mediated by the induction of Skp2 mRNA translation in eIF4E-dependent mechanism. These results provide a new insight into the role of the Akt/mTORC1/eIF4E axis in tumourigenesis. Akt-dependent Skp2 mRNA translation is also required for mitotic clonal expansion (MCE)--the earliest event in adipogenesis. Skp2 re-expression in Akt-deficient preadipocytes, which are impaired in adipogenesis, is sufficient to restore adipogenesis. These results uncover the mechanism by which Akt mediates adipogenesis.


Assuntos
Adipogenia , Transformação Celular Neoplásica , Inibição de Contato , Fator de Iniciação 4E em Eucariotos/metabolismo , Proteína Oncogênica v-akt/metabolismo , Proteínas/metabolismo , Proteínas Quinases Associadas a Fase S/biossíntese , Animais , Proliferação de Células , Células Cultivadas , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Knockout , Complexos Multiproteicos , Biossíntese de Proteínas , Serina-Treonina Quinases TOR
19.
BMC Cardiovasc Disord ; 16: 41, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26879576

RESUMO

BACKGROUND: In the early stage of diabetes, the cardiac ejection fraction is preserved, despite the existence of the subclinical cardiac dysfunction to some extent. However, the detailed phenotype of this dysfunction and the underlying mechanism remain unclear. To improve our understanding of this issue, we used low-dose STZ and high-fat diet to induce type 2 diabetic models in rats. The effects and the mechanism associated with the early stages of the disease were analyzed. METHODS: The type 2 diabetic mellitus (T2DM) in SD rats were induced through 30 mg/kg STZ and high-fat diet. Two-dimensional spackle-tracking echocardiography (STE) and the dobutamine test were performed to examine the cardiac function. Calcium transients of left ventricular myocytes were detected and the related intracellular signalling factors were analyzed by western blotting. RESULTS: After 6-weeks, T2DM rats in left ventricular (LV) diastole showed decreased global and segment strain(S) levels (P < 0.05), both in the radial and circumferential directions. Strain rate (Sr) abatement occurred in three segments in the radial and circumferential directions (P < 0.05), and the radial global Sr also decreased (P < 0.05). In the systolic LV, radial Sr was reduced, except the segment of the anterior septum, and the Sr of the lateral wall and post septum decreased in the circumferential direction (P < 0.05). Conventional M-mode echocardiography failed to detect significant alterations of cardiac performance between the two groups even after 12 weeks, and the decreased ejection fraction (EF%), fractional shortening (FS%) and end-systolic diameters (ESD) could be detected only under stress conditions induced by dobutamine (P < 0.05). In terms of calcium transients in cardiac myocytes, the Tpeak in model rats at 6 weeks was not affected, while the Tdecay1/2 was higher than that of the controls (P < 0.05), and both showed a dose-dependent delay after isoproterenol treatment (P < 0.05). Western blot analysis showed that in 6-week T2DM rats, myocardial p-PLB expression was elevated, whereas p-CaMKII, p-AMPK and Sirt1 were significantly down-regulated (P < 0.05). CONCLUSION: A rat model of T2DM was established by low dose STZ and a high-fat diet. LV deformation was observed in the early stages of T2DM in association with the delay of Ca(2+) transients in cardiomyocytes due to the decreased phosphorylation of CaMKII. Myocardial metabolism remodeling might contribute to the early LV function and calcium transportation abnormalities.


Assuntos
Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Dieta Hiperlipídica , Ventrículos do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/etiologia , Modelos Animais de Doenças , Ecocardiografia , Ecocardiografia sob Estresse , Eletroforese em Gel de Poliacrilamida , Ventrículos do Coração/citologia , Ventrículos do Coração/diagnóstico por imagem , Immunoblotting , Fosfoproteínas/metabolismo , Ratos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sirtuína 1/metabolismo
20.
Surg Endosc ; 30(5): 2127-31, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26205558

RESUMO

BACKGROUND: This study was designed to evaluate the feasibility and efficacy of metallic clips assisted with foreign body forceps closing the gastric wall defect after endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs). METHODS: Eighteen patients with gastric SMTs originated from the muscularis propria were treated by EFR between September 2012 and June 2014. Twelve patients underwent endoscopic closure of the gastric wall defects after EFR with endoloop and metallic clips (endoloop string suture method, ESSM), and six patients with clips and foreign body forceps (clips assisted with foreign body forceps clip method, CFCM). RESULTS: No significant differences existed between the two groups in terms of demographics, clinical characteristics, and the size of the gastric wall defects. The average time spent in closing the gastric wall defects (14.83 ± 1.94 min for the CFCM group and 22.42 ± 5.73 min for the ESSM group) and hospitalization fees of the CFCM group were significantly lower than those of the ESSM group. The average hospitalization time of the two groups had no statistical significance. No single case had surgical intervention or complications, such as gastric bleeding, perforation, peritonitis, or abdominal abscess. CONCLUSION: The CFCM and the ESSM are safe and effective techniques for gastric defect closure after EFR for gastric SMTs. Because of the "chopsticks effect," the CFCM more suitable for the lesions located at the gastric fundus, the greater curvature or anterior wall of the gastric body and gastric antrum.


Assuntos
Ressecção Endoscópica de Mucosa , Endoscopia Gastrointestinal , Gastroscopia , Neoplasias Gástricas/cirurgia , Instrumentos Cirúrgicos , Feminino , Corpos Estranhos/cirurgia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/cirurgia , Estudos Retrospectivos , Técnicas de Sutura , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA