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1.
Entropy (Basel) ; 22(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33286133

RESUMO

In underwater acoustic signal processing, direction of arrival (DOA) estimation can provide important information for target tracking and localization. To address underdetermined wideband signal processing in underwater passive detection system, this paper proposes a novel underdetermined wideband DOA estimation method equipped with the nested array (NA) using focused atomic norm minimization (ANM), where the signal source number detection is accomplished by information theory criteria. In the proposed DOA estimation method, especially, after vectoring the covariance matrix of each frequency bin, each corresponding obtained vector is focused into the predefined frequency bin by focused matrix. Then, the collected averaged vector is considered as virtual array model, whose steering vector exhibits the Vandermonde structure in terms of the obtained virtual array geometries. Further, the new covariance matrix is recovered based on ANM by semi-definite programming (SDP), which utilizes the information of the Toeplitz structure. Finally, the Root-MUSIC algorithm is applied to estimate the DOAs. Simulation results show that the proposed method outperforms other underdetermined DOA estimation methods based on information theory in term of higher estimation accuracy.

2.
Amino Acids ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245424

RESUMO

As a promising cell therapy, neural crest-derived ectoderm mesenchymal stem cells (EMSCs) secrete high amounts of extracellular matrix (ECM) and neurotrophic factors, promoting neural stem cell (NSC) differentiation into neuronal lineages and aiding tissue regeneration. Additionally, the forced overexpression of secreted proteins can increase the therapeutic efficacy of the secretome. Tissue transglutaminase (TG2) is a ubiquitously expressed member of the transglutaminase family of calcium-dependent crosslinking enzymes, which can stabilize the ECM, inducing smart or living biomaterial to stimulate differentiation and enhance the neurogenesis of NSCs. In this study, we examined the neuronal differentiation of NSCs induced by TG2 gene-modified EMSCs (TG2-EMSCs) in a co-culture model directly. Two weeks after initiating differentiation, levels of the neuronal markers, tubulin beta 3 class III and growth-associated protein 43, were higher in NSCs in the TG2-EMSC co-culture group and those of the astrocytic marker glial fibrillary acidic protein were lower, compared with the control group. These results were confirmed by immunofluorescence, and laminin, fibronectin and sonic hedgehog (Shh) contributed to this effect. The results of western blot analysis and the enzyme-linked immunoassay showed that after TG2-EMSCs were co-cultured for 2 weeks, they expressed much higher levels of Shh than the control group. Moreover, the sustained release of Shh was observed in the TG2-EMSC co-culture group. Overall, our findings indicate that EMSCs can induce the differentiation of NSCs, of which TG2-EMSCs can promote the differentiation of NSCs compared with EMSCs.

3.
Clin Spine Surg ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32815852

RESUMO

PURPOSE: Anterior controllable antedisplacement and fusion (ACAF) has been reported to be a safe and effective technique. However, incompletely hoisted vertebrae (IV) were found in the postoperative images. This study aims to analyze the causes and prevention of IV. METHODS: The ACAF-treated case series subjects were retrospectively reviewed. The vertebrae were separated into the IV group and completely hoisted vertebrae (CV) group according to the gap between the vertebrae and plate. The radiographic data, degree of cervical lordosis, bone mineral density, number of hoisted vertebrae, operative time, blood loss, and Japanese Orthopaedic Association score were compared between the patients with IV and the patients without IV. RESULTS: A total of 248 vertebrae were hoisted in the enrolled patients. Intervertebral disc height in the IV group was 3.7±0.4 mm, which is significantly lower than that in the CV group. The anterior or posterior overhanging lip, osteoporosis, and oblique osteotomy troughs and hinges existing after osteotomy were found to be impingements preventing the hoisting of the vertebrae. There were no differences in the age, sex, degree of cervical lordosis, number of hoisted vertebrae, and neurological improvement rate between the groups of patients with and without IV. CONCLUSIONS: Lower intervertebral space height and impingements preventing hoisting were found to be possible causes of IV in ACAF. Measures to prevent the problem should be carried out.

4.
Oral Dis ; 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32731298

RESUMO

OBJECTIVES: To assess the magnetic resonance imaging (MRI) in predicting tumour's depth of invasion (DOI) of tongue cancer by comparing to pathology and to determine the cut-off value of MRI-derived DOI for lymph node metastasis. PATIENTS AND METHODS: In a retrospective analysis, 156 patients with newly diagnosed tongue cancer were included. Tumour's DOI was compared between MRI measurement and pathology by Pearson correlation coefficient and paired t test. The accuracy of MRI-derived DOI was compared to the pathological DOI. The relationship between MRI-derived DOI and cervical lymph node metastasis was calculated by receiver operating characteristic curve. RESULTS: Tumour's DOI was well correlated between MRI measurement and pathology with correlation coefficients of 0.77. MRI-derived DOI was 3.4 mm (28%) larger than pathology. The accuracy of MRI in deciding pathological DOI was 67.9%. The cut-off value of MRI-derived DOI was 10.5 mm for lymph node metastasis of tongue cancer. CONCLUSION: Magnetic resonance imaging can be used as a reference to determine tumour's DOI of tongue cancer. Tumour with MRI-derived DOI larger than 10.5 mm deserves simultaneous neck dissection at initial surgery.

5.
Mol Metab ; 37: 100980, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305491

RESUMO

OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) can achieve long-term remission of type 2 diabetes. However, the specific molecular mechanism through which this occurs has remained largely elusive. Bile acid signaling through the nuclear hormone receptor farnesoid X receptor (FXR) exerts beneficial effects after sleeve gastrectomy (VSG), which has similar effects to RYGB. Therefore, we investigated whether FXR signaling is necessary to mediate glycemic control after RYGB. METHODS: RYGB or sham surgery was performed in high-fat diet-induced obese FXR-/- (knockout) and FXR+/+ (wild type) littermates. Sham-operated mice were fed ad libitum (S-AL) or by weight matching (S-WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance tests, insulin tolerance tests, and homeostatic model assessment of insulin resistance were performed. RESULTS: RYGB surgery decreases body weight and fat mass in WT and FXR-KO mice. RYGB surgery has similar effects on food intake and energy expenditure independent of genotype. In addition, body weight-independent improvements in glucose control were attenuated in FXR -/- relative to FXR +/+ mice after RYGB. Furthermore, pharmacologic blockade of the glucagon-like peptide-1 receptor (GLP-1R) blunts the glucoregulatory effects of RYGB in FXR +/+ but not in FXR -/- mice at 4 weeks after surgery. CONCLUSIONS: These results suggest that FXR signaling is not required for the weight loss up to 16 weeks after RYGB. Although most of the improvements in glucose homeostasis are secondary to RYGB-induced weight loss in wild type mice, FXR signaling contributes to glycemic control after RYGB in a body weight-independent manner, which might be mediated by an FXR-GLP-1 axis during the early postoperative period.

6.
Bioinformatics ; 36(10): 3077-3083, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32053156

RESUMO

MOTIVATION: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide- and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods. RESULTS: We developed BionoiNet, a new deep learning-based framework implementing a popular ResNet model for image classification. BionoiNet first transforms the molecular structures of ligand-binding sites to 2D Voronoi diagrams, which are then used as the input to a pretrained convolutional neural network classifier. The ResNet model generalizes well to unseen data achieving the accuracy of 85.6% for nucleotide- and 91.3% for heme-binding pockets. BionoiNet also computes significance scores of pocket atoms, called BionoiScores, to provide meaningful insights into their interactions with ligand molecules. BionoiNet is a lightweight alternative to computationally expensive 3D architectures. AVAILABILITY AND IMPLEMENTATION: BionoiNet is implemented in Python with the source code freely available at: https://github.com/CSBG-LSU/BionoiNet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Neurais de Computação , Proteínas , Sítios de Ligação , Ligantes , Estrutura Molecular
7.
Obes Surg ; 30(4): 1410-1416, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31939006

RESUMO

BACKGROUND: Although bariatric surgery can achieve sustained weight loss, there are major differences in the magnitude of weight change post-operatively. Reduced resting energy expenditure (REE) plays an important role in unsatisfactory weight loss effect by contributing to positive energy balance. OBJECTIVES: To identify pre- and post-surgical predictors related to satisfactory percent of total weight loss (%TWL) in Chinese individuals with obesity after laparoscopic sleeve gastrectomy (LSG). METHODS: A retrospective cohort study was conducted in 97 ethnic Chinese with mean body mass index (BMI) of 37.2 kg/m2, focusing on body composition, anthropometric and metabolic energy expenditure parameters, and %TWL before and 6 months after LSG. Patients were divided post-operatively into those with or without satisfactory %TWL (%TWL ≥ 20%). Multiple stepwise logistic regression analysis was used to identify predictors. RESULTS: Satisfactory %TWL was achieved in 53 (54.6%) patients 6 months after surgery. The univariate analysis of post-operative variables showed that patients with satisfactory %TWL had significantly higher resting energy expenditure/body weight (REE/BW) and lower respiratory quotient (RQ) than those who did not (P < 0.001). Multiple stepwise logistic regression analysis indicated that REE/BW and RQ were closely associated with satisfactory %TWL (P = 0.004, P = 0.023, respectively). %TWL was positively correlated with changes in BMI, percent of fat-free mass (FFM%), REE/BW, and RQ. CONCLUSIONS: Higher REE/BW and lower RQ resulting from LSG correlated with satisfactory %TWL in Chinese patients with obesity. The maintenance of FFM might be an important factor linking %TWL and REE/BW.

8.
J Immunol ; 204(3): 632-643, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31852753

RESUMO

Thioredoxin-interacting protein (TXNIP) is a multifunctional protein that functions in tumor suppression, oxidative stress, and inflammatory responses. However, how TXNIP functions during microbial infections is rarely reported. In this study, we demonstrate that Brucella infection decreased TXNIP expression to promote its intracellular growth in macrophages by decreasing the production of NO and reactive oxygen species (ROS). Following Brucella abortus infection, TXNIP knockout RAW264.7 cells produced significantly lower levels of NO and ROS, compared with wild-type RAW264.7 cells. Inducible NO synthase (iNOS) inhibitor treatment reduced NO levels, which resulted in a dose-dependent restoration of TXNIP expression, demonstrating that the expression of TXNIP is regulated by NO. In addition, the expression of iNOS and the production of NO were dependent on the type IV secretion system of Brucella Moreover, Brucella infection reduced TXNIP expression in bone marrow-derived macrophages and mouse lung and spleen. Knocked down of the TXNIP expression in bone marrow-derived macrophages increased intracellular survival of Brucella These findings revealed the following: 1) TXNIP is a novel molecule to promote Brucella intracellular survival by reducing the production of NO and ROS; 2) a negative feedback-regulation system of NO confers protection against iNOS-mediated antibacterial effects. The elucidation of this mechanism may reveal a novel host surveillance pathway for bacterial intracellular survival.


Assuntos
Brucella abortus/fisiologia , Brucelose/metabolismo , Proteínas de Transporte/metabolismo , Macrófagos/imunologia , Tiorredoxinas/metabolismo , Animais , Brucelose/microbiologia , Proteínas de Transporte/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Espaço Intracelular/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/genética
9.
Genome Biol ; 20(1): 207, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610793

RESUMO

BACKGROUND: Large palindromes (inverted repeats) make up substantial proportions of mammalian sex chromosomes, often contain genes, and have high rates of structural variation arising via ectopic recombination. As a result, they underlie many genomic disorders. Maintenance of the palindromic structure by gene conversion between the arms has been documented, but over longer time periods, palindromes are remarkably labile. Mechanisms of origin and loss of palindromes have, however, received little attention. RESULTS: Here, we use fiber-FISH, 10x Genomics Linked-Read sequencing, and breakpoint PCR sequencing to characterize the structural variation of the P8 palindrome on the human Y chromosome, which contains two copies of the VCY (Variable Charge Y) gene. We find a deletion of almost an entire arm of the palindrome, leading to death of the palindrome, a size increase by recruitment of adjacent sequence, and other complex changes including the formation of an entire new palindrome nearby. Together, these changes are found in ~ 1% of men, and we can assign likely molecular mechanisms to these mutational events. As a result, healthy men can have 1-4 copies of VCY. CONCLUSIONS: Gross changes, especially duplications, in palindrome structure can be relatively frequent and facilitate the evolution of sex chromosomes in humans, and potentially also in other mammalian species.


Assuntos
Cromossomos Humanos Y , Sequências Repetidas Invertidas , Proteínas Nucleares/genética , Sequência de Bases , Variações do Número de Cópias de DNA , Humanos
10.
Biomicrofluidics ; 13(4): 044108, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31372195

RESUMO

Two-dimensional (2D) cell culture is not ideal for traditional drug screening, because 2D culture does not accurately mimic the physiological microenvironment of tumor cells. Thus, a drug-screening system which more closely mimics the microenvironment of in vivo tumors is necessary. Here, we present a biomimicking bilayer microfluidic device that can facilitate antitumor drug screening. The microfluidic device consists of two polydimethylsiloxane (PDMS) pieces with channels which are separated by a semipermeable membrane to allow water, oxygen, and nutrition supply, while preventing cell migration. The channels embedded on the two PDMS pieces overlap each other over a long distance to ensure a larger exchange area to mimic the blood vessel-tumor model. High concentrations of endothelial cells (EC) are first seeded onto the membrane through the apical channel, and after a two-day culture, a confluent EC monolayer forms. Tumor spheroid-laden Matrigel is then seeded into the basal channel. After the Matrigel is cured, the device is ready for drug testing. Paclitaxel is used as the model drug for testing. Confocal microscopy and ImageJ are used to assess the efficacy of different concentrations of paclitaxel, and optical coherence tomography (OCT) is employed to determine the tumor volumetric change after the drug treatment. The results indicate that the proposed bilayer microfluidic device in combination with confocal and OCT optical characterization provide an efficient platform for antitumor drug testing.

11.
Exp Ther Med ; 18(2): 1258-1266, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31363370

RESUMO

Clobetasol propionate (Clo) is a potent topical glucocorticoid and a potential remyelinating agent that has been approved by the U.S. Food and Drug Administration. However, the effect of Clo on neural stem cells (NSCs) remains largely unknown. The aim of the present study was to investigate the effect of Clo on the differentiation of NSCs in vitro. NSCs were isolated from mouse embryonic brain tissues and expanded in vitro. The effect of Clo on NSC viability was examined using an MTT assay. Differentiating NSCs were treated with 5 or 10 µM Clo, or with DMSO control, and the degree of differentiation was examined following culture in stem cell differentiation induction medium for 7 days. The effect of Clo on NSC differentiation was assessed using immunocytochemistry and western blot analyses. The results revealed that Clo significantly increased NSC viability compared with the DMSO control group. Treatment with Clo also significantly increased the number of NSCs that differentiated into growth associated protein 43 positive neurons and corresponding axon lengths were also significantly increased. In addition, treatment with Clo significantly increased the number of myelin basic protein positive oligodendrocytes and decreased the number of glial fibrillary acidic protein positive astrocytes. Furthermore, inhibition of the sonic hedgehog and AMP-activated protein kinase signaling pathways inhibited Clo-induced NSC differentiation, and treatment with Clo upregulated the expression of several neurotrophic factors. In conclusion, the results of the current study suggest that Clo may have a potential therapeutic benefit in neurological disorders affecting oligodendrocytes and neurons.

12.
Carbohydr Polym ; 222: 115024, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320088

RESUMO

Gelation and rheological behaviors of cellulose/CO2-based reversible ionic liquid (RIL)/DMSO solutions were investigated. The exponents of specific viscosity ηsp versus concentration c were determined for wood pulp (WP) and microcrystalline cellulose (MCC) solutions. The complex viscosity acquired using oscillatory shear closely follows the steady shear viscosity, thus revealing the applicability of Cox-Merz rule. The influence of RIL content in the solvent on apparent viscosities, activation energy, intrinsic viscosities, specific viscosity-c[η] master curve, and relaxation time were also investigated. Gelation occurred in this cellulose solution system due to thermal-induced CO2 release from the decomposition of the CO2-based reversible ionic liquid. The formed gel was stable in air, but re-dissolved when exposed to CO2, indicating the switch-on and switch-off effects of CO2 in cellulose dissolution and gelation.

13.
Mol Med Rep ; 20(3): 2763-2773, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322240

RESUMO

Ectomesenchymal stem cells (EMSCs) represent a type of adult stem cells derived from the cranial neural crest. These cells are capable of self­renewal and have the potential for multidirectional differentiation. Tissue transglutaminase type 2 (TG2) is a ubiquitously expressed member of the transglutaminase family of Ca2+­dependent crosslinking enzymes. However, the effect of TG2 on neural differentiation and proliferation of EMSCs remains unknown. To determine whether TG2 improves EMSC proliferation and neurogenesis, a stable TG2­overexpressing EMSC cell line (TG2­EMSCs) was established by using an adenovirus system. Immunofluorescence staining and western blot analyses demonstrated that TG2 overexpression had beneficial effects on the rate of EMSC neurogenesis, and that the proliferative capacity of TG2­EMSCs was higher than that of controls. Furthermore, the results of western blotting revealed that extracellular matrix (ECM) and neurotrophic factors were upregulated during the differentiation of TG2­EMSCs. Notably, TG2­EMSC transplantation in an animal model of spinal cord injury (SCI), TG2­EMSCs differentiated into neuron­like cells and enhanced the repair of SCI. Taken together, these results demonstrated that TG2 gene transfection may offer a novel strategy to enhance EMSC proliferation and neurogenesis in vivo and in vitro, which may ultimately facilitate EMSC­based transplantation therapy in patients with SCI.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Neurogênese , Traumatismos da Medula Espinal/terapia , Transglutaminases/genética , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/transplante , Animais , Linhagem Celular , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Regulação para Cima
14.
Hum Mol Genet ; 28(16): 2785-2798, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108506

RESUMO

Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.


Assuntos
Cromossomos Humanos Y , Variações do Número de Cópias de DNA , Evolução Molecular , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Hibridização Genômica Comparativa , Genoma Humano , Genômica/métodos , Humanos , Hibridização in Situ Fluorescente , Masculino , Família Multigênica , Mutação , Filogenia , Espermatozoides/metabolismo
15.
Obes Surg ; 29(7): 2318-2337, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31016456

RESUMO

We herein summarize the available literature on the effects of bariatric surgery (BS) on energy expenditure in individuals with obesity. We conducted a systematic literature review, and 35 prospective studies met our inclusion criteria. The findings indicate that BS contributes to increased diet-induced thermogenesis (DIT) and decreased total energy expenditure (TEE) and resting energy expenditure (REE) in patients with obesity. The meta-analysis demonstrated a significant decrease in TEE and REE within 6 months following BS. With the sustained decrease in REE, there was no further decrease in TEE between the 6- and 12-month follow-up. Increased DIT might explain the variance between the patterns of REE and TEE change. The postoperative decrease in REE/FFM and increase in REE/BW were observed. The changes in substrate utilization might be consistent with the change in the respiration quotient postoperatively.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Metabolismo Energético/fisiologia , Obesidade , Humanos , Obesidade/fisiopatologia , Obesidade/cirurgia , Termogênese/fisiologia
16.
J Vis Exp ; (144)2019 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-30799861

RESUMO

Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, high-throughput imaging modalities utilizing bright field or fluorescence detection, are unable to resolve the overall 3D structure of the tumor spheroid due to limited light penetration, diffusion of fluorescent dyes and depth-resolvability. Recently, our lab demonstrated the use of optical coherence tomography (OCT), a label-free and non-destructive 3D imaging modality, to perform longitudinal characterization of multicellular tumor spheroids in a 96-well plate. OCT was capable of obtaining 3D morphological and physiological information of tumor spheroids growing up to about 600 µm in height. In this article, we demonstrate a high-throughput OCT (HT-OCT) imaging system that scans the whole multi-well plate and obtains 3D OCT data of tumor spheroids automatically. We describe the details of the HT-OCT system and construction guidelines in the protocol. From the 3D OCT data, one can visualize the overall structure of the spheroid with 3D rendered and orthogonal slices, characterize the longitudinal growth curve of the tumor spheroid based on the morphological information of size and volume, and monitor the growth of the dead-cell regions in the tumor spheroid based on optical intrinsic attenuation contrast. We show that HT-OCT can be used as a high-throughput imaging modality for drug screening as well as characterizing biofabricated samples.


Assuntos
Imageamento Tridimensional/métodos , Monitorização Fisiológica , Neoplasias/patologia , Esferoides Celulares/patologia , Tomografia de Coerência Óptica/métodos , Humanos , Células Tumorais Cultivadas
17.
Adv Mater ; 31(10): e1806861, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30633831

RESUMO

The therapeutic efficiency of allogenic/intrinsic neural stem cells (NSCs) after spinal cord injury is severely compromised because the hostile niche at the lesion site incurs massive astroglial but not neuronal differentiation of NSCs. Although many attempts are made to reconstruct a permissive niche for nerve regeneration, solely using a living cell material to build an all-in-one, multifunctional, permissive niche for promoting neuronal while inhibiting astroglial differentiation of NSCs is not reported. Here, ectomesenchymal stem cells (EMSCs) are reported to serve as a living, smart material that creates a permissive, all-in-one niche which provides neurotrophic factors, extracellular matrix molecules, cell-cell contact, and favorable substrate stiffness for directing NSC differentiation. Interestingly, in this all-in-one niche, a corresponding all-in-one signal-sensing platform is assembled through recruiting various niche signaling molecules into lipid rafts for promoting neuronal differentiation of NSCs, and meanwhile, inhibiting astrocyte overproliferation through the connexin43/YAP/14-3-3θ pathway. In vivo studies confirm that EMSCs can promote intrinsic NSC neuronal differentiation and domesticating astrocyte behaviors for nerve regeneration. Collectively, this study represents an all-in-one niche created by a single-cell material-EMSCs for directing NSC differentiation.


Assuntos
Comunicação Celular/efeitos dos fármacos , Microdomínios da Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Neurais/metabolismo , Nicho de Células-Tronco/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Humanos , Regeneração Nervosa/fisiologia
18.
Curr Biol ; 29(1): 149-157.e3, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30581024

RESUMO

The Americas were the last inhabitable continents to be occupied by humans, with a growing multidisciplinary consensus for entry 15-25 thousand years ago (kya) from northeast Asia via the former Beringia land bridge [1-4]. Autosomal DNA analyses have dated the separation of Native American ancestors from the Asian gene pool to 23 kya or later [5, 6] and mtDNA analyses to ∼25 kya [7], followed by isolation ("Beringian Standstill" [8, 9]) for 2.4-9 ky and then a rapid expansion throughout the Americas. Here, we present a calibrated sequence-based analysis of 222 Native American and relevant Eurasian Y chromosomes (24 new) from haplogroups Q and C [10], with four major conclusions. First, we identify three to four independent lineages as autochthonous and likely founders: the major Q-M3 and rarer Q-CTS1780 present throughout the Americas, the very rare C3-MPB373 in South America, and possibly the C3-P39/Z30536 in North America. Second, from the divergence times and Eurasian/American distribution of lineages, we estimate a Beringian Standstill duration of 2.7 ky or 4.6 ky, according to alternative models, and entry south of the ice sheet after 19.5 kya. Third, we describe the star-like expansion of Q-M848 (within Q-M3) starting at 15 kya [11] in the Americas, followed by establishment of substantial spatial structure in South America by 12 kya. Fourth, the deep branches of the Q-CTS1780 lineage present at low frequencies throughout the Americas today [12] may reflect a separate out-of-Beringia dispersal after the melting of the glaciers at the end of the Pleistocene.


Assuntos
Grupo com Ancestrais Nativos do Continente Americano/genética , Cromossomos Humanos Y/genética , DNA Antigo/análise , Genótipo , Migração Humana , Arqueologia , DNA Mitocondrial/genética , Feminino , Genoma Humano/genética , Humanos , Masculino
19.
Pharmacoepidemiol Drug Saf ; 27(11): 1257-1264, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30232823

RESUMO

PURPOSE: Signal evaluation is considered to be a tedious process owing to the large number of disproportional signals detected. This study aimed to apply a biclustering algorithm in the spontaneous reporting system of China and to obtain the optimal parameters. The biclustering algorithm is expected to improve the efficiency of signal evaluation by identifying similar signal groups. METHODS: Information component (IC) was the method used for disproportionality analysis. By using IC thresholds of various strengths (0.05-4.00), the original quantitative data matrix was transformed into 80 different binary data matrices, where each cell contained either a 1 or 0. The biclustering results were obtained using a total of 720 Bimax algorithm parameters (minimal number of columns and rows was 3, 4, or 5). Next, the optimal parameters were determined through the comprehensive evaluation of the rank sum ration. Finally, we examined the biclustering results under the optimal parameters and evaluated the effect of biclustering analysis on adverse drug reaction (ADR) data in China. RESULTS: The optimal strength of the IC threshold was 0.80, and the minimum number of rows and columns was 3. After taxonomic evaluation, we also found that 1836 biclusters (42.8%) contained similar drugs or similar ADRs, which accounted for 72.3% of signals unevaluated. CONCLUSIONS: Applying biclustering analysis in spontaneous reporting system could provide support in confirming unrecognized ADRs, identifying rare ADRs, and screening drug-ADR pairs, which need more attention. Biclustering algorithm could improve the efficiency of signal detection and evaluation in China.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Algoritmos , Mineração de Dados/métodos , Bases de Dados Factuais/estatística & dados numéricos , Farmacoepidemiologia/métodos , China/epidemiologia , Análise por Conglomerados , Humanos , Farmacovigilância
20.
Sci Rep ; 8(1): 6837, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717201

RESUMO

A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.


Assuntos
Técnicas de Cultura de Células , Ensaios de Seleção de Medicamentos Antitumorais , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Doxorrubicina/farmacologia , Células HCT116 , Humanos , Paclitaxel/farmacologia
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