Biomedical subjects

Yong Fan

Publications and source records attributed to Yong Fan.

15 recordsLinked to original sources

PubMed2025

Modeling early gastrulation in human blastoids with DNA methylation patterns of natural blastocysts.

Blastoids are a promising model for studying early human embryogenesis, but current models have limitations in post-implantation development and lack comprehensive epigenetic assessments, especially regarding genomic imprinting. These issues can lead to failures in accurately modeling early embryonic development. In this study, we developed a high-fidelity blastoid model using 4 chemicals + leukemia inhibitory factor (LIF) (4CL) naive human pluripotent stem cells (hPSCs) (4CL blastoids). 4CL blastoids closely resemble human blastocysts in morphology and transcriptional profiles, exhibiting similar DNA methylation and gene imprinting patterns. By extending the 3D culture to 14 days, these blastoids mimic early gastrulation, demonstrating the specification and migration of cells. They also show the transcriptional signature of hemogenic angioblast (HAB) cells at Carnegie stage 6 (CS6). This model bridges pre- and post-implantation stages, offering valuable insights into early tissue formation and human development.

Humans↗

PubMed2007

Establishment of customized mouse stem cell lines by sequential nuclear transfer.

Therapeutic cloning, whereby embryonic stem cells (ESCs) are derived from nuclear transfer (NT) embryos, may play a major role in the new era of regenerative medicine. In this study we established forty nuclear transfer-ESC (NT-ESC) lines that were derived from NT embryos of different donor cell types or passages. We found that NT-ESCs were capable of forming embryoid bodies. In addition, NT-ESCs expressed pluripotency stem cell markers in vitro and could differentiate into embryonic tissues in vivo. NT embryos from early passage R1 donor cells were able to form full term developed pups, whereas those from late passage R1 ES donor cells lost the potential for reprogramming that is essential for live birth. We subsequently established sequential NT-R1-ESC lines that were developed from NT blastocyst of late passage R1 ESC donors. However, these NT-R1-ESC lines, when used as nuclear transfer donors at their early passages, failed to result in live pups. This indicates that the therapeutic cloning process using sequential NT-ESCs may not rescue the developmental deficiencies that resided in previous donor generations.

Animals↗

PubMed2006

Detection of prodromal Alzheimer's disease via pattern classification of magnetic resonance imaging.

We report evidence that computer-based high-dimensional pattern classification of magnetic resonance imaging (MRI) detects patterns of brain structure characterizing mild cognitive impairment (MCI), often a prodromal phase of Alzheimer's disease (AD). Ninety percent diagnostic accuracy was achieved, using cross-validation, for 30 participants in the Baltimore Longitudinal Study of Aging. Retrospective evaluation of serial scans obtained during prior years revealed gradual increases in structural abnormality for the MCI group, often before clinical symptoms, but slower increase for individuals remaining cognitively normal. Detecting complex patterns of brain abnormality in very early stages of cognitive impairment has pivotal importance for the detection and management of AD.

Aged↗

PubMed2006

Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism.

FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. However, the underlying mechanism and physiology remain unknown. We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. FoxO1 gain of function, as a result of adenovirus-mediated or transgenic expression, augmented hepatic gluconeogenesis, accompanied by decreased glycogen content and increased fat deposition in liver. Mice with excessive FoxO1 activity exhibited impaired glucose tolerance. Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. FoxO1 expression becomes deregulated, culminating in increased nuclear localization and accounting for its increased transcription activity in livers of both high fat-induced obese mice and diabetic db/db mice. Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes.

Animals↗

PubMed2006

Rehabilitation of adaptive immunity and regeneration of beta cells.

Type 1 Diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic insulin-producing beta cells that most frequently occurs in genetically predisposed children. Recent observations illustrating the regenerative capability of the endocrine pancreas in addition to advances in stem cell and gene therapy technologies enable the exploration of alternatives to allogeneic islet transplantation. Living-cell-mediated approaches can abrogate autoimmunity and the consequent destruction of beta cells without the need for immunosuppressive drugs. Such approaches can be used as a foundation for new protocols that more easily translate to the clinical setting. The twin goals of controlling autoimmune disease and promoting stable regeneration of insulin-producing beta cells should be considered the cornerstones of the successful development of a cure for this chronic disease.

Animals↗

PubMed2006

Facilitating physiologic self-regeneration: a step beyond islet cell replacement.

Type 1 diabetes (T1D) is an autoimmune disease, the clinical onset of which most frequently presents in children and adolescents who are genetically predisposed. T1D is characterized by specific insulin-producing beta cell destruction. The well-differentiated and specialized islet beta cells seem to physiologically retain the ability to compensate for the cells lost by reproducing themselves, whereas undifferentiated cell sources may help in generating new ones, even while the autoimmune process takes place. Diabetes clinical onset, i.e., establishment of a detectable, chronic hyperglycemia, occurs at a critical stage when autoimmunity, having acted for a while, supersedes the regenerative effort and reduces the number of beta cells below the physiologic threshold at which the produced insulin becomes insufficient for the body's needs. Clinical solutions aimed at avoiding cumbersome daily insulin administrations by the reestablishment of physiologic insulin production, like whole pancreas or pancreatic islet allotransplantation, are limited by the scarcity of pancreas donors and by the toxic effects of the immunosuppressive drugs administered to prevent rejection. However, new accumulating evidence suggests that, once autoimmunity is abrogated, the endocrine pancreas properties may be sufficient to allow the physiological regenerative process to restore endogenous insulin production, even after the disease has become clinically manifest. Knowledge of these properties of the endocrine pancreas suggests the testing of reliable and clinically translatable protocols for obliterating autoimmunity, thus allowing the regeneration of the patient's own endocrine cells. The safe induction of an autoimmunity-free status might become a new promising therapy for T1D.

Animals↗

PubMed2006

A functional comparison of mature human dendritic cells prepared in fluorinated ethylene-propylene bags or polystyrene flasks.

BACKGROUND: Fluorinated ethylene-propylene (FEP) bags have been used instead of polystyrene (PS) flasks for ex vivo clinical-scale production of human dendritic cells (DCs) to facilitate closed-system recovery of these highly adherent cells. To assess the impact of DC culture on this nonadherent surface, the function of DCs generated in FEP and PS was compared. STUDY DESIGN AND METHODS: Cell yield, phenotype, cytokine production, migration, and antigen-presenting activity were measured in DCs prepared from peripheral blood monocytes in FEP bags or PS flasks with medium supplemented with serum, interleukin (IL)-4, and granulocyte-macrophage-colony-stimulating factor for 5 days to induce DC differentiation and CD40L or poly(I:C) plus interferon-gamma to promote maturation. RESULTS: DCs cultured in FEP or PS had comparable cell yield, viability, and CD83 and CCR7 expression. DCs generated in FEP, however, produced significantly less IL-12 and IL-10 during maturation, and differences persisted on rechallenge after harvest. FEP-cultured DCs migrated spontaneously or in response to CCR7 ligand more actively than PS-cultured DCs, but this difference was not significant. Mature DCs prepared in FEP and PS were equipotent in stimulating peptide-specific CD8 T-cell expansion in vitro. CONCLUSION: FEP- and PS-cultured DCs are similar in phenotype and in some functional measures, but FEP markedly reduces DC production of IL-12 and IL-10. This phenomenon presumably reflects intracellular changes linked to the absence of a surface for firm cell adherence. Given the importance of these cytokines in the immune response, these changes could have a significant impact on DC function in vivo.

Antigen-Presenting Cells↗

PubMed2006

[Application of bronchoscopic lung volume reduction using one-way flap device in sheep model of heterogeneous emphysema].

OBJECTIVE: To evaluate the effectiveness of bronchoscopic lung volume reduction (BLVR) using one way flap device in sheep model of heterogeneous emphysema. METHODS: Six 6-month sheep (weight: 20-30 kg) were treated with localized papain instillations to generate heterogeneous emphysema, subsequently underwent BLVR using one way-flap device at subsegment. Lung functional residual capacity (FRC) was analyzed before and 8 weeks after operation. Animals were euthanized at the 8-week time point. Lungs were removed en bloc and inflated with a super syringe to look for areas of gross collapse. Samples were collected from collapsed and non-collapsed areas, fixed in 10% buffered formalin, made paraffin section and stained with hematoxylin-eosin (HE) to observe morphologic change of bronchi. RESULTS: BLVR was well tolerated without complications, and it reduced lung volumes (change in residual volume 49.5%). There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung,improved respiratory function safely and consistently. CONCLUSION: BLVR using one-way flap device is a minimally invasive procedure and the stimulus of the devices to walls of bronchi is slight, moreover, the technique may attain effectiveness of surgery. Therefore maybe it will be a perspective treatment of chronic obstructive pulmonary disease.

Animals↗

PubMed2006

[Effect of hospice care on the quality of life and psychological state of aged mortal inpatients].

OBJECTIVE: To investigate the influence of hospice care on the life quality and psychological state of aged mortal inpatients. METHODS: Seventy-six aged patients were randomly divided into 2 groups (n=38). The research group was treated with hospice care, while the control group was treated with conventional nursing. Before and after more than one month of the interference, the quality of life, social support, satisfied degree, anxiety, and depression mood were investigated. RESULTS: All the indexes, such as total scale of life quality, appetite, spirit, sleep, family comprehension and coordination, recognition of cancer, attitude to therapy, and facial expression of the mortal inpatients after the interference, were raised and higher than those of the controls (P<0.05 or P<0.01). Life satisfaction index and the total scale of social support and subjective support, utilization ratio of support were raised and higher than those of the controls (P<0.05 or P<0.01). The level of anxiety and depression was decreased and lower than the control (P<0.05 or P<0.01). CONCLUSION: Hospice care can raise the life quality, subjective support, utilization ratio of support and life satisfaction of aged mortal inpatients. It could decrease the negative mood, such as anxiety and depression and improve the psychological state.

Aged↗

PubMed2005

Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities.

CONTEXT: Neuroanatomic abnormalities in schizophrenia may underlie behavioral manifestations. Characterization of such abnormalities is required for interpreting functional data. Frontotemporal abnormalities have been documented by using predetermined region-of-interest approaches, but deformation-based morphometry permits examination of the entire brain. OBJECTIVES: To perform whole-brain analyses of structural differences between patients with schizophrenia and controls, to examine sex and medication effects, and to apply a high-dimensional nonlinear pattern classification technique to quantify the degree of separation between patients and controls, thereby testing the potential of this new technique as an aid to diagnostic procedures. DESIGN: Whole-brain morphologic analysis using high-dimensional shape transformations. SETTING: Schizophrenia Research Center, University of Pennsylvania Medical Center. PARTICIPANTS: Neuroleptic-naïve and previously treated patients with DSM-IV schizophrenia (n = 69) and sociodemographically matched controls (n = 79). MAIN OUTCOME MEASURES: Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the brain. RESULTS: Magnetic resonance images showed reduced gray matter and increased ventricular cerebrospinal fluid volumes in patients with schizophrenia in the whole brain and in specific foci: the hippocampus and adjacent white matter, the cingulate and orbitofrontal cortex, the frontotemporal and parietotemporal areas, and the occipital areas near the lingual gyrus. The classifier had a mean classification accuracy of 81.1% for men and women combined (82% for women and 85% for men, when each group was treated separately), determined via cross-validation. CONCLUSIONS: This study confirms previous findings of reduced frontotemporal volumes and suggests new hypotheses, especially involving occipital association and speech production areas. It also suggests finer localization of volume reduction in the hippocampus and other limbic structures and in the frontal lobe. Pattern classification showed high sensitivity and specificity for the diagnosis of schizophrenia, suggesting the potential utility of magnetic resonance imaging as a diagnostic aid.

Adult↗

PubMed2005

Classification of structural images via high-dimensional image warping, robust feature extraction, and SVM.

This paper presents a method for classification of medical images, using machine learning and deformation-based morphometry. A morphological representation of the anatomy of interest is first obtained using high-dimensional template warping, from which regions that display strong correlations between morphological measurements and the classification (clinical) variable are extracted using a watershed segmentation, taking into account the regional smoothness of the correlation map which is estimated by a cross-validation strategy in order to achieve robustness to outliers. A Support Vector Machine-Recursive Feature Elimination (SVM-RFE) technique is then used to rank computed features from the extracted regions, according to their effect on the leave-one-out error bound. Finally, SVM classification is applied using the best set of features, and it is tested using leave-one-out. The results from a group of 61 brain images of female normal controls and schizophrenia patients demonstrate not only high classification accuracy (91.8%) and steep ROC curves, but also exceptional stability with respect to the number of selected features and the SVM kernel size.

Algorithms↗

PubMed2005

Consistent estimation of cardiac motions by 4D image registration.

A 4D image registration method is proposed for consistent estimation of cardiac motion from MR image sequences. Under this 4D registration framework, all 3D cardiac images taken at different time-points are registered simultaneously, and motion estimated is enforced to be spatiotemporally smooth, thereby overcoming potential limitations of some methods that typically estimate cardiac deformation sequentially from one frame to another, instead of treating the entire set of images as a 4D volume. To facilitate our image matching process, an attribute vector is designed for each point in the image to include intensity, boundary and geometric moment invariants (GMIs). Hierarchical registration of two image sequences is achieved by using the most distinctive points for initial registration of two sequences and gradually adding less-distinctive points for refinement of registration. Experimental results on real data demonstrate good performance of the proposed method in registering cardiac images and estimating motions from cardiac image sequences.

Algorithms↗

PubMed2004

[Re-survey on epidemiological history of 1 091 probable cases with severe acute respiratory syndrome in Beijing].

OBJECTIVE: To know their real epidemiological histories in 1,091 probale cases of severe acute respiratory syndrome (SARS) without definite history of contact with SARS patients in the first survey. METHODS: All the probable SARS cases until June 9, 2003 without definite history of contact with SARS patients in the first epidemiological survey were included in a re-survey with questionnaire. The second survey was carried out during June 9 to 30, 2003. RESULTS: The results showed that history of contact with other SARS patients was obtained in 15.9% of 1 091 probale SRAS cases in the second survey, transmission of SARS to others was found in 10.5% of them, and source of infection in hospital was found in 46.5%. Comprehensive judgement based on epidemiological history showed that probale history of contact with SARS patients could be found in 72.9% of 1,091 probale cases of SARS in the second survey. CONCLUSION: Source of infection could be found through additional survey in part of probale cases of SARS without it in initial epidemiological survey.

China↗

PubMed2002

Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells.

Recent experiments show that hematopoietic progenitor cell populations contain endothelial precursor cells. We have isolated a population of CD34(+) cells that expresses fibroblast growth factor receptor-1 (FGFR-1) and that differentiates into endothelial cells in vitro. We find that 4.5% +/- 2.1% of CD34(+) cells isolated from bone marrow, cord blood, and mobilized peripheral blood express FGFR-1 and that viable CD34(+)FGFR(+) cells are small, with little granularity, and express both primitive hematopoietic and endothelial markers on their surface. The primitive hematopoietic markers AC133, c-kit, and Thy-1 are coexpressed by 75%, 85%, and 64% of CD34(+)FGFR(+) cells, respectively. Most of the CD34(+)FGFR(+) cells also express antigens found on endothelial cells, such as CD31, vascular endothelial growth factor receptor-2, and the endothelial-specific cell surface marker, vascular endothelial cadherin (VE-cadherin), whereas 56% to 60% of the cells express Tie, Tek, and the endothelial-specific marker, P1H12. The CD34(+)FGFR(+) population is enriched in cells expressing endothelial-specific antigens compared with the CD34(+) population. Isolated CD34(+)FGFR(+) cells grow slowly in culture, are stimulated by fibroblast growth factor-2 and vascular endothelial growth factor, and give rise to cells that express von Willebrand factor and VE-cadherin and that incorporate acetylated low-density lipoprotein. These experiments show that FGFR-1 is expressed by a subpopulation of CD34(+) cells that give rise to endothelial cells in vitro, indicating that this population contains endothelial stem/progenitor cells.

Cell Culture Techniques↗

PubMed2002

Volumetric segmentation of brain images using parallel genetic algorithms.

Active model-based segmentation has frequently been used in medical image processing with considerable success. Although the active model-based method was initially viewed as an optimization problem, most researchers implement it as a partial differential equation solution. The advantages and disadvantages of the active model-based method are distinct: speed and stability. To improve its performance, a parallel genetic algorithm-based active model method is proposed and applied to segment the lateral ventricles from magnetic resonance brain images. First, an objective function is defined. Then one instance surface was extracted using the finite-difference method-based active model and used to initialize the first generation of a parallel genetic algorithm. Finally, the parallel genetic algorithm is employed to refine the result. We demonstrate that the method successfully overcomes numerical instability and is capable of generating an accurate and robust anatomic descriptor for complex objects in the human brain, such as the lateral ventricles.

Algorithms↗