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1.
Cell Death Dis ; 11(1): 39, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959745

RESUMO

Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK.

2.
PLoS One ; 14(12): e0204717, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800593

RESUMO

Kemp's ridley sea turtles were on the verge of extinction in the 1960s. While these sea turtles have slowly recovered, they are still critically endangered. In the last few years, the number of strandings on the beaches of Cape Cod, Massachusetts has increased by nearly an order of magnitude relative to preceding decades. This study uses a combination of ocean observations and a well-respected ocean model to investigate the causes and transport of cold-stunned sea turtles in Cape Cod Bay. After validating the model using satellite-tracked drifters and local temperature moorings, ocean currents were examined in Cape Cod Bay in an attempt to explain stranding locations as observed by volunteers and, for some years, backtracking was conducted to examine the potential source regions. The general finding of this study is that sub 10.5°C water temperatures in combination with persistently strong wind stress (>0.4 Pa), results in increased strandings along particular sections of the coast and are dependent on the wind direction. However, it is still uncertain where in the water column the majority of cold-stunned turtles reside and, if many of them are on the surface, considerable work will need to be done to incorporate the direct effects of wind and waves on the advective processes.

3.
Onco Targets Ther ; 12: 10469-10475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819527

RESUMO

Objective: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is relatively rare, and risk factors of this disease are still not well understood. This study aims to identify clinical features and prognostic factors of PT-DLBCL patients. Methods: Thirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed. Results: The median age of the patients was 57 (range 36-76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4-6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan-Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028). Conclusion: Our work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS.

4.
Pestic Biochem Physiol ; 161: 33-46, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685194

RESUMO

Chitin is a structural component of the arthropod cuticular exoskeleton and the peritrophic matrix of the gut, which play crucial roles in growth and development. In the past few decades, our understanding of the composition, biosynthesis, assembly, degradation, and regulation of chitinous structures has increased. Many chemicals have been developed that target chitin biosynthesis (benzoyphenyl ureas, etoxazole), chitin degradation (allosamidin, psammaplin), and chitin regulation (benzoyl hydrazines), thus resulting in molting deformities and lethality. In addition, proteins that disrupt chitin structures, such as lectins, proteases, and chitinases have been utilized to halt feeding and induce mortality. Chitin-degrading enzymes, such as chitinases are also useful for improving the efficacy of bio-insecticides. Transgenic plants, baculoviruses, fungi, and bacteria have been engineered to express chitinases from a variety of organisms for control of arthropod pests. In addition, RNA interference targeting genes involved in chitin pathways and structures are now being investigated for the development of environmentally friendly pest management strategies. This review describes the chemicals and proteins used to target chitin structures and enzymes for arthropod pest management, as well as pest management strategies based upon these compounds, such as plant-incorporated-protectants and recombinant entomopathogens. Recent advances in RNA interference-based pest management, and how this technology can be used to target chitin pathways and structures are also discussed.

5.
Cell Biochem Funct ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709594

RESUMO

Classical Hodgkin lymphoma (cHL) is a particular kind of malignant tumour that originates from the B cells. The malignant phenotype of cHL is, at least in part, maintained by epigenetic aberrations, which primarily consist of abnormal histone methylation and acetylation. Progress has been made in clinical trials concerning the histone deacetylases inhibitors (HDACis) in cHL. Also, some demethylation regimens could serve the purpose of preventing and treating tumours. Programmed death-ligand receptor 1 (PD-L1, CD274) inhibitors or apoptosis receptor 1 (PD-1, CD279) inhibitors are used in treating patients with relapsed cHL in recent years. Academic researches indicated that PD-1/PD-L1 inhibitors, including nivolumab and pembrolizumab, demonstrate remarkable activity in relapsed cHL. In addition, in recent years, a close association between epigenetic aberrations and immune escape has been explored in cHL. DNA methyltransferase (DNMT) inhibitors, HDACis, and immune checkpoint blockade exhibit synergistic effects. Thus, this review aims to provide an overview on the epigenetic abnormalities of cHL and its effect on immune escape, in order to explore the optimal combination approach to treat the disease. SIGNIFICANCE OF THE STUDY: Cancer Statistics 2018 reported that more than 8000 new cases of Hodgkin lymphoma were diagnosed. In recent years, PD-1/PD-L1 inhibitors for cHL have been utilized, and the therapeutic strategies of HDACis combined with PD-1/PD-L1 inhibitors have been raised. It is critical for improving the efficacy and decreasing the toxicity in treating the patients with cHL.

6.
Front Genet ; 10: 807, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552101

RESUMO

Polyploidy has contributed to the divergence and domestication of plants; however, estimation of the relative roles that different types of polyploidy have played during evolution has been difficult. Unbalanced and balanced gene removal was previously related to allopolyploidies and autopolyploidies, respectively. Here, to infer the types of polyploidies and evaluate their evolutionary effects, we devised a statistic, the Polyploidy-index or P-index, to characterize the degree of divergence between subgenomes of a polyploidy, to find whether there has been a balanced or unbalanced gene removal from the homoeologous regions. Based on a P-index threshold of 0.3 that distinguishes between known or previously inferred allo- or autopolyploidies, we found that 87.5% of 24 angiosperm paleo-polyploidies were likely produced by allopolyploidizations, responsible for establishment of major tribes such as Poaceae and Fabaceae, and large groups such as monocots and eudicots. These findings suggest that >99.7% of plant genomes likely derived directly from allopolyploidies, with autopolyploidies responsible for the establishment of only a few small genera, including Glycine, Malus, and Populus, each containing tens of species. Overall, these findings show that polyploids with high divergence between subgenomes (presumably allopolyploids) established the major plant groups, possibly through secondary contact between previously isolated populations and hybrid vigor associated with their re-joining.

7.
Theranostics ; 9(12): 3501-3514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281493

RESUMO

Identification of proper agents to increase or activate UCP1+ cells in adipose tissues remains a potent therapeutic strategy to combat obesity. Screening systems for UCP1 activators have been previously established and allow for unbiased discovery of effective compound(s). Methods: A previously established Ucp1-2A-GFP reporter system was applied to a chemical library containing 33 phosphatase inhibitors. Compounds that can significantly activate UCP1 expression were further tested in vivo in mouse adipose tissues. Possible underlying mechanism was explored via RNA profiling, CMAP analysis, CRISPR targeting as well as inhibitor treatments. Results: We identified BML-260, a known potent inhibitor of the dual-specific phosphatase JSP-1, that significantly increased UCP1 expression in both brown and white adipocytes. BML-260 treatment also activated oxidative phosphorylation genes, increased mitochondrial activity as well as heat generation in vitro and in vivo. Mechanistic studies revealed that effect of BML-260 on adipocytes was partly through activated CREB, STAT3 and PPAR signaling pathways, and was unexpectedly JSP-1 independent. Conclusion: The rhodanine derivate BML-260 was previously identified to be a JSP-1 inhibitor, and thus was proposed to treat inflammatory and proliferative disorders associated with dysfunctional JNK signaling. This work provides evidences that BML-260 can also exert a JSP-1-independent effect in activating UCP1 and thermogenesis in adipocytes, and be potentially applied to treat obesity.

8.
Biomedicine (Taipei) ; 9(2): 10, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124456

RESUMO

BACKGROUND: Various systems have employed with the objective to reduce the time from emergency medical services contact to balloon inflammation for ST-elevation myocardial infraction (STEMI) patients. The WCACG message system was used to an alternative communication platform to improve confirmation of the diagnosis and movement to treatment, resulted in shorten the door-to-balloon (D-to-B) time for STEMI patients. METHODS: We collected 366 STEMI patients admitted at the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Department of Cardiology, during the period from June 2013 to October 2015. The patients were divided into two groups one underwent the current GC processes and the other group was handled using WCACG system. We compared between two groups with several indicators including D-to-B time, duration of hospitalization, associated costs, and incidence of adverse cardiovascular events. RESULTS: The results show that the new method with WCACG system significantly reduced the average D-to-B time (from 100.42 ± 25.14 mins to 79.81 ± 20.51 mins, P < 0.05) compared to the GC processes, and also reduced the duration, costs and undesirable cardiac incidence during hospitalization. CONCLUSIONS: The modified WCACG process is an applicable system to save pieces of time and efficiently integrate the opinions of experts in emergency.

9.
Adv Exp Med Biol ; 1142: 169-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31102247

RESUMO

Chitin is a structural constituent of extracellular matrices including the cuticle of the exoskeleton and the peritrophic matrix (PM) of the midgut in arthropods. Chitin chains are synthesized through multiple biochemical reactions, organized in several hierarchical levels and associated with various proteins that give their unique physicochemical characteristics of the cuticle and PM. Because, arthropod growth and morphogenesis are dependent on the capability of remodeling chitin-containing structures, chitin biosynthesis and degradation are highly regulated, allowing ecdysis and regeneration of the cuticle and PM. Over the past 20 years, much progress has been made in understanding the physiological functions of chitinous matrices. In this chapter, we mainly discussed the biochemical processes of chitin biosynthesis, modification and degradation, and various enzymes involved in these processes. We also discussed cuticular proteins and PM proteins, which largely determine the physicochemical properties of the cuticle and PM. Although rapid advances in genomics, proteomics, RNA interference, and other technologies have considerably facilitated our research in chitin biosynthesis, modification, and metabolism in recent years, many aspects of these processes are still partially understood. Further research is needed in understanding how the structural organization of chitin synthase in plasma membrane accommodate chitin biosynthesis, transport of chitin chain across the plasma membrane, and release of the chitin chain from the enzyme. Other research is also needed in elucidating the roles of chitin deacetylases in chitin organization and the mechanism controlling the formation of different types of chitin in arthropods.


Assuntos
Artrópodes , Quitina/metabolismo , Amidoidrolases , Animais , Quitina Sintase
10.
J Biomed Inform ; 93: 103144, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30905736

RESUMO

Influenza rapidly spreads in seasonal epidemics and imposes a considerable economic burden on hospitals and other healthcare costs. Thus, predicting the propagation of influenza accurately is crucial in preventing influenza outbreaks and protecting public health. Most current studies focus on the spread simulation of influenza. However, few studies have investigated the dependencies between meteorological variables and influenza activity. This study develops a non-parametric model based on Gaussian process regression for influenza prediction considering meteorological effect to capture temporal dependencies hidden in influenza time series. To identify the most explanatory external variables, L1-regularization is applied to identify meteorology factor subsets, and three types of covariance functions are designed to characterize non-stationary and periodic behavior in influenza activity. The dependencies of diseases and meteorology are modeled through the designed cross-covariance function. A real case in Shenzhen, China was studied to validate our proposed model along with comparisons to recently developed multivariate statistical models for influenza prediction. Results show that our proposed influenza prediction approach achieves superior performance in terms of one-week-ahead prediction of influenza-like illness.

11.
J Insect Physiol ; 114: 109-115, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30902530

RESUMO

The peritrophic matrix (PM) is an extracellular, semi-permeable biocomposite that lines the midgut of most insects. The PM serves as the first defense in the midgut to resist microorganisms such as viruses, bacteria and other pathogens, and to protect epithelial cells from mechanical damage. The PM also separates the midgut lumen into different compartments, which play important roles in nutrient ingestion and digestion. The PM is a highly dynamic structure that consists mainly of chitin fibers cross-linked by proteins, glycoproteins, and proteoglycans. The PM is continuously biosynthesized, assembled, and degraded in response to feeding and development. Chitin chains are synthesized by several enzymes and organized in several hierarchical levels, in which various PM-associated proteins appear to be essential for maintaining the structural integrity and physiological function of the PM. This review summarizes research advances on molecular components of the PM and their functions, as well as related proteins and enzymes that contribute to PM formation and modification. Crucial gaps in our current understanding of the PM are also addressed.


Assuntos
Quitina/biossíntese , Locusta migratoria/metabolismo , Animais , Trato Gastrointestinal/metabolismo
12.
Cell Rep ; 26(4): 884-892.e4, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30673611

RESUMO

DNA variants in the SLC16A11 coding region were identified to be strongly associated with type 2 diabetes (T2DM) in a Mexican population. Previous studies suggested that these variants disrupt SLC16A11 function and therefore proposed to revive SLC16A11 levels or activity to achieve therapeutic benefit. However, with knockout mouse models, here we show that Slc16a11 depletion has no significant metabolic defects. Further studies demonstrate that reconstitution of the mutant, but not the wild-type Slc16a11, in the liver of knockout mice causes more triglyceride accumulation and induction of insulin resistance via upregulation of lipin 1, suggesting gaining of aberrant functions of the mutant protein that affects lipid metabolism. Our findings offer a different explanation to the function of these diabetic variants, challenging the concept of enhancing SLC16A11 function to treat T2DM. The contradictory results by our and previous studies suggest that how the SLC16A11 locus contributes to human metabolism warrants further investigation.

13.
Sci Total Environ ; 652: 1013-1021, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30380469

RESUMO

Hand, foot and mouth disease (HFMD) is a public health issue in China, and its incidence in Guangdong Province is higher than the national average. Previous studies have found climatic factors have an influential role in the transmission of HFMD. Internet search technology has been shown to predict some infectious disease epidemics and is a potential resource in tracking epidemics in countries where the use of Internet search index data is prevalent. This study aims to improve the prediction of HFMD in two Chinese cities, Shantou and Shenzhen in Guangdong Province, applying both meteorological data and Baidu search indices to create a HFMD forecasting model. To this end, the relationship between meteorological factors and HFMD was found to be linear in both cities, while the relationship between search engine data and HFMD was not consistent. The results of our study suggest that using both Internet search and meteorological data can improve the prediction of HFMD incidence. Using comparative analysis of both cities, we posit that improved quality search indices enhance prediction of HFMD.


Assuntos
Doença de Mão, Pé e Boca/epidemiologia , Conceitos Meteorológicos , China/epidemiologia , Previsões , Humanos , Incidência , Internet , Meteorologia , Prevalência , Saúde Pública
14.
Leuk Lymphoma ; 60(4): 934-939, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30277105

RESUMO

Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALB ≤ 35g/L, staging ≥ IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan-Meier analyses indicated that patients with large (≥3 cm) and deep lesions (≥11 mm) had an inferior OS (p = .01 and .039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed.

15.
Cancer Lett ; 443: 167-178, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30550850

RESUMO

MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter. Melatonin also blocked NF-κB nuclear translocation and suppressed NF-κB binding to the COX-2 promoter, thereby suppressing the expression of COX-2. In addition, clinical samples revealed that melatonin exerts anti-leukemic activity in primary MLL-r leukemia blasts ex vivo. In vivo, the mice treated with melatonin experienced a larger reduction in leukemic burden than the control group in a MLL-r leukemia xenograft mouse model. Collectively, these results suggest that melatonin inhibits MLL-rearranged leukemia through suppressing the RBFOX3/hTERT and NF-κB/COX-2 signaling pathways. Our findings provide new insights into the role of melatonin for MLL-r leukemia treatment.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia/tratamento farmacológico , Melatonina/administração & dosagem , Proteína de Leucina Linfoide-Mieloide/genética , Transdução de Sinais/efeitos dos fármacos , Animais , Antígenos Nucleares/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , Ciclo-Oxigenase 2/genética , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia/genética , Leucemia/metabolismo , Masculino , Melatonina/farmacologia , Camundongos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Telomerase/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Exp Ther Med ; 16(5): 3827-3834, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30344659

RESUMO

At present there is no consensus on the treatment of classical Hodgkin's lymphoma (CHL) following relapse. The aim of the present study was to access the class I-selective histone deacetylase (HDAC) inhibitor (HDACI) MGCD0103 on the expression levels of Bcl-2, nuclear factor (NF)-κB and programmed death-ligand 1 (PD-L1) in CHL, to explore the possible therapeutic value of MGCD0103 in combined relative target drugs for patients with CHL. In L1236 and L428 cell lines, apoptosis and cell cycle stage were identified using flow cytometry, and the effects of HDACI on CHL were assessed in terms of Bcl-2, NF-κB and PD-L1 expression levels, which were detected by western blotting and co-focusing experiments. The results demonstrated that MGCD0103 could induce cell apoptosis and cell cycle arrest, down-regulate Bcl-2 and increase NF-κB and PD-L1 expression levels in L1236 and L428 cell lines. MGCD0103 decreases Bcl-2 levels and upregulates PD-L1, which indicates that the combined use of HDACIs and a PD-L1 inhibitor in theory may improve treatment outcomes in patients with CHL. MGCD0103 may also up-regulate NF-κB, which seems to induce resistance towards anti-apoptotic drugs. Clinical trials combining HDACIs with NF-κB and/or PD-L1 inhibitors should be designed to further improve treatment outcomes for patients with CHL.

17.
EBioMedicine ; 37: 344-355, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30348622

RESUMO

BACKGROUND: The pharmacological activation of thermogenesis in brown adipose tissue has long been considered promising strategies to treat obesity. However, identification of safe and effective agents remains a challenge. In this study, we addressed this challenge by developing a cellular system with a fluorescence readout, and applied in a high-throughput manner to screen for FDA-approved drugs that may activate endogenous UCP1 expression in adipocytes. METHODS: We have generated a Ucp1-2A-GFP reporter mouse, in which GFP intensity serves as a surrogate of the endogenous expression level of UCP1 protein; and immortalized brown adipocytes were derived from this mouse model and applied in drug screening. Candidate drugs were further tested in mouse models either fed with normal chow or high fat diet to induce obesity. FINDINGS: By using the cellular screening platform, we identified a group of FDA-approved drugs that can upregulate UCP1 expression in brown adipocyte, including previously known UCP1 activators and new candidate drugs. Further studies focusing on a previously unreported drug-sutent, revealed that sutent treatment could increase the energy expenditure and inhibit lipid synthesis in mouse adipose and liver tissues, resulting in improved metabolism and resistance to obesity. INTERPRETATION: This study offered an easy-to-use cellular screening system for UCP1 activators, and provided a candidate list of FDA-approved drugs that can potentially treat obesity. Further study of these candidates may shed new light on the drug discovery towards obesity. FUND: National Key Research and Development Program and the Strategic Priority Research Program of the Chinese Academy of Sciences, etc. (250 words).


Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Desacopladora 1/biossíntese , Adipócitos Marrons/patologia , Tecido Adiposo Marrom/patologia , Animais , Linhagem Celular Transformada , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Camundongos , Camundongos Transgênicos , Proteína Desacopladora 1/genética , Estados Unidos , United States Food and Drug Administration
18.
Comput Intell Neurosci ; 2018: 1943565, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147716

RESUMO

Confusion is a complex cognitive state that is prevalent during learning and problem-solving. The aim of this study is to explore the brain activity reflected by electroencephalography (EEG) during a confusing state induced by two kinds of information insufficiencies during mathematical problem-solving, namely, an explicit situation that clearly lacked information and an implicit situation in which the missing information was hidden in the problem itself, and whether there is an EEG difference between these two situations. Two experimental tasks and three control tasks were created. Short time Fourier transformation (STFT) was used for time-frequency analysis; then the alpha task-related-power (TRP) changes and distributions, which are closely related to cognitive processing, were calculated, and repeated measures ANOVA were performed to find the significant difference between task conditions. The results showed that the alpha power decreased significantly in the regions related to calculation when the participants encountered both explicit and implicit information insufficiency tasks compared to the control tasks, suggesting that confusion can cause more brain activity in the cortical regions related to the tasks that induce confusion. In addition, the implicit information insufficiency task elicited more activity in the parietal and right temporal regions, whereas the explicit information insufficiency task elicited additional activity in the frontal lobe, which revealed that the frontal region is related to the processing of novel or unfamiliar information and the parietal-temporal regions are involved in sustained attention or reorientation during confusing states induced by information insufficiency. In conclusion, this study has preliminarily investigated the EEG characteristics of confusion states, suggests that EEG is a promising methodology to detect confusion, and provides a basis for future studies aiming to achieve automatic recognition of confusing states.


Assuntos
Encéfalo/fisiologia , Eletroencefalografia , Conceitos Matemáticos , Resolução de Problemas/fisiologia , Análise de Variância , Atenção/fisiologia , Interfaces Cérebro-Computador , Compreensão/fisiologia , Sincronização Cortical , Análise de Fourier , Humanos , Masculino , Testes Neuropsicológicos , Processamento de Sinais Assistido por Computador
19.
Stem Cell Reports ; 11(1): 22-31, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29861165

RESUMO

Hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) offer a promising cell resource for disease modeling and transplantation. However, differentiated HLCs exhibit an immature phenotype and comprise a heterogeneous population. Thus, a better understanding of HLC differentiation will improve the likelihood of future application. Here, by taking advantage of CRISPR-Cas9-based genome-wide screening technology and a high-throughput hPSC screening platform with a reporter readout, we identified several potential genetic regulators of HLC differentiation. By using a chemical screening approach within our platform, we also identified compounds that can further promote HLC differentiation and preserve the characteristics of in vitro cultured primary hepatocytes. Remarkably, both screenings identified histone deacetylase 3 (HDAC3) as a key regulator in hepatic differentiation. Mechanistically, HDAC3 formed a complex with liver transcriptional factors, e.g., HNF4, and co-regulated the transcriptional program during hepatic differentiation. This study highlights a broadly useful approach for studying and optimizing hPSC differentiation.


Assuntos
Diferenciação Celular , Hepatócitos/citologia , Hepatócitos/metabolismo , Histona Desacetilases/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Sistemas CRISPR-Cas , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Células Cultivadas , Citometria de Fluxo , Edição de Genes , Regulação da Expressão Gênica no Desenvolvimento , Marcação de Genes , Genes Reporter , Genes abl , Fator 4 Nuclear de Hepatócito/metabolismo , Histona Desacetilases/genética , Humanos , Modelos Biológicos , Fenilenodiaminas/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-29550466

RESUMO

PURPOSE: A computational model based on clinical data from pancreatic cancer patients has been successfully created and used for predicting tumor sizes in primary and metastasis sites and survival time from kinetics of tumor cells, such as growth rate, metastasis rate and mutation rate, etc. Whether this computational model could be fitted or necessary modification of some parameters for fitting in mice is unknown. Here, we developed a computational model in mice for spontaneous metastasis to simulate the process of tumor metastasis based on the mathematical frameworks. METHODS: The spontaneous melanoma metastasis model in mice was used for assessing the fitting accuracy between the mathematical model and the experimental data and evaluating the efficacy of anticancer agents, as well as the invasion assay. RESULTS: According to the modified model, most of parameters including growth rate, mutation rate and metastasis rate, which were used to describe the whole metastatic course in mice were calculated based on the experimental analysis. Furthermore, only measurement of the growth rate of cancer in the primary site was required to predict the survival time. Our predicted results of the overall survival (OS) extension of mice were close to the clinical outcomes after treated with four clinical intervention strategies of CVD, Paclitaxel, Dartmouth and Temozolomide. And predictive efficacy of anticancer drug using the model matches well the factual experimental data in mice. CONCLUSIONS: The mathematical model is more economical and efficient for evaluating the tumor metastasis and could be used to screen the anti-cancer and anti-metastatic medicine by shortening the periods of assessment of OS extension in preclinical trials.


Assuntos
Antineoplásicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Modelos Teóricos , Metástase Neoplásica/prevenção & controle , Animais , Feminino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Taxa de Sobrevida , Fatores de Tempo
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