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Biomedical subjects

Yi He

Publications and source records attributed to Yi He.

At least 19 recordsLinked to original sources
PubMed2026

Day + 30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15-35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention. METHODS: In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 5 × 10-6) on day + 30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy. RESULTS: Among the 136 patients, 37 patients (27.2%) had detectable FLT3-ITD clones on day + 30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, p = 0.001). Notably, FLT3-ITD-positive patients who received FLT3 inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, FLT3-ITD-negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD-free survival: hazard ratio (HR) = 0.25 (0.03-2.11), p = 0.204; OS: HR = 0.20 (0.02-1.70), p = 0.142). CONCLUSIONS: This is the first study to demonstrate that detection of minimal FLT3-ITD clones at the fixed time point of day + 30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.

Humans↗
PubMed2006

Understanding the nonfouling mechanism of surfaces through molecular simulations of sugar-based self-assembled monolayers.

This paper presents a molecular simulation study of the interactions of a protein (lysozyme) with self-assembled monolayers (SAMs) of mannitol and sorbitol terminated alkanethiols in the presence of explicit water molecules and ions. The all-atom simulations were performed to calculate the force generated on the protein as a function of its distance above the SAM surfaces. The structural and dynamic properties of water molecules both above the SAM surfaces and around the SAM head groups were analyzed to provide a better understanding of the nonfouling behavior of the sugar-based SAM surfaces. Results from this work suggest that both mannitol and sorbitol SAMs generate a tightly bound, structured water layer around the SAM chains. This hydration layer creates a repulsive force on the protein when it approaches the surface, resulting in a nonfouling surface despite the presence of hydrogen-bond donor groups. This work demonstrates the importance of strong surface-water interactions for surface resistance to nonspecific protein adsorption.

Adsorption↗
PubMed2006

Downregulation of cyclooxygenase-2 expression and activation of caspase-3 are involved in peroxisome proliferator-activated receptor-gamma agonists induced apoptosis in human monocyte leukemia cells in vitro.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a transcription factor important in fat metabolism and PPAR-gamma agonists were recently demonstrated to affect proliferation, differentiation, and apoptosis of different cell types. In the present study, two PPAR-gamma agonists, 15-deoxy-delta (12,14)-prostaglandin J2 (15d-PGJ2) and a synthetic PPAR-gamma agonist troglitazone (TGZ), were used to investigate activated PPAR-gamma-induced apoptosis on human monocyte leukemia U937 and Mono Mac 6 cells in vitro. The results showed that both U937 and Mono Mac 6 cells demonstrated constitutive activation of COX-2 expression; treatment by 15d-PGJ2 and TGZ could induce apoptosis remarkably in human monocyte leukemia cells by disruption of mitochondrial membrane potential, activation of caspase-3, and causing cleavage of the caspase substrate poly (ADP-ribose) polymerase (PARP). Further studies revealed that treatment by both 15d-PGJ2 and TGZ remarkably downregulated COX-2 expression in these two kind of monocyte leukemia cells as measured by reverse transcriptase PCR (RT-PCR) and Western blot. Furthermore, the expression of Bcl-2 and Bcl-Xl and Mcl-1 was downregulated while Bax expression was upregulated concurrently after the cells were treated by these two agonists, and no variations were found in other Bcl-2 family members such as Bak, Bid, and Bad. Taken together, our results demonstrate for the first time that downregulation of cyclooxygenase-2 expression, disruption of mitochondrial membrane potential, activation of caspase-3, downregulation of Bcl-2, Bcl-Xl, and Mcl-1, and upregulation of Bax are involved in PPAR-gamma agonists-induced apoptosis in these two human monocyte leukemia cells.

Apoptosis↗
PubMed2006

Molecular simulation studies of the structure of phosphorylcholine self-assembled monolayers.

We report a study of the structure of phosphorylcholine self-assembled monolayers (PC-SAMs) on Au(111) surfaces using both molecular mechanics (MM) and molecular dynamics (MD) simulation techniques. The lattice structure (i.e., packing densities and patterns) of the PC chains was determined first, by examining the packing energies of different structures by MM simulations in an implicit solvent. The chain orientation (i.e., antiparallel and parallel arrangements of the PC head groups) was then evaluated. The initial azimuthal angles of the PC chains were also adjusted to ensure that the optimal lattice structure was found. Finally, the two most probable lattice structures were solvated with explicit water molecules and their energies were compared after 1.5 ns of MD simulations to verify the optimal structures obtained from MM. We found that the optimal lattice structure of the PC-SAM corresponds to a radical7 x radical7 R19degree lattice structure (i.e., surface coverage of 50.4 A(2)molecule) with a parallel arrangement of the head groups. The corresponding thickness of the optimal PC-SAM is 13.4 A which is in agreement with that from experiments. The head groups of the PC chains are aligned on the surface in such a way that their dipole components are minimized. The P-->N vector of the head groups forms an angle of 82 degrees with respect to the surface normal. The tilt direction of molecular chains was observed to be towards their next nearest neighbor.

Adsorption↗
PubMed2006

Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia.

Cyclin-dependent kinase 5 (Cdk5) is a unique member of the CDK family. It is predominantly expressed in postmitotic neurons and has been implicated in neuronal plasticity. The present study showed that Cdk5 and p35 were expressed in primary sensory and dorsal horn neurons, while p25, an N-terminal truncated derivative of p35, could only be detected in the dorsal horn neurons. Importantly, in the case of control rats, the p35 protein level was much higher in small- and medium-diameter DRG neurons than it was in large neurons. Following CFA injection, Cdk5 activity was upregulated in both primary sensory and dorsal horn neurons. Cdk5 activation in DRG neurons required p35, whereas p25 was required in the dorsal horn. Intrathecal pretreatment with Roscovitine, a specific inhibitor of Cdk5 activity, and intrathecal delivery of the DN-Cdk5(N144) gene both alleviated CFA-induced heat hyperalgesia but not mechanical allodynia. In contrast, overexpression of Cdk5, p35 or p25 in primary sensory and dorsal horn neurons significantly enhanced heat hyperalgesia. We conclude that Cdk5/p35 and Cdk5/p25 complexes in primary sensory and dorsal horn neurons may potentially be involved in nociceptive transmission after inflammation and may be employed in synaptic plasticity underlying pain hypersensitization.

Animals↗
PubMed2006

Strong resistance of a thin crystalline layer of balanced charged groups to protein adsorption.

Resistance of mixed self-assembled monolayers (SAMs) with various counter-charged terminal groups of different valence and protonation/deprotonation states to nonspecific protein adsorption is investigated. It is demonstrated that excellent nonfouling surfaces can be readily constructed from mixed positively and negatively charged components of equal valence in a wide range of thiol solution compositions. Furthermore, the lattice structure of one of the mixed SAM systems studied is revealed by atomic force microscopy (AFM) to be (5.2 +/- 0.2 A x 5.2 +/- 0.2 A)60 degrees . Results indicate that the packing structure of mixed charged SAMs is determined by strong charge-charge interactions of the terminal groups rather than S-Au and chain-chain interactions. This work provides direct evidence that conformational flexibility is not required for protein resistance of a surface and even a single compact layer of charged groups of balanced charge with a crystalline structure can resist nonspecific protein adsorption, suggesting that tightly bound water molecules on the topmost part of the mixed SAMs play a dominant role in surface resistance to nonspecific protein adsorption.

Adsorption↗
PubMed2006

Single drop liquid-liquid-liquid microextraction of methamphetamine and amphetamine in urine.

Single drop liquid-liquid-liquid microextraction (LLLME) combined with high performance liquid chromatography (HPLC)-UV detection was investigated for the determination of a popular drug of abuse, methamphetamine (MAP), and its major metabolite, amphetamine (AP), in urine samples. The target compounds were extracted from NaOH modified sample solution to a thin layer of organic solvent membrane, and back-extracted to an acidic acceptor drop suspended on the tip of a 50-microL HPLC syringe in the aforementioned organic layer. This syringe was also used for direct injection after extraction. Factors affecting extraction efficiency were studied. At optimal conditions, the overall enrichment factor (EF) was 500-fold for AP and 730-fold for MAP, respectively. The method exhibited a wide linear range (1.0-1500 microg/L), low detection limit (0.5 microg/L), and good repeatability (RSD<5.0%) for both analytes. The feasibility of the method was demonstrated by the analysis of human urine samples.

Amphetamine↗
PubMed2006

Role of CDK5 in neuroprotection from serum deprivation by mu-opioid receptor agonist.

Cyclin-dependent kinase 5 (CDK5), a unique member of the CDK family of cyclin-dependent kinases, is predominantly expressed in postmitotic neurons with proposed roles in both cell survival and programmed cell death. To understand how CDK5 participates in such disparate cellular outcomes, we investigated whether activation of CDK5 could mediate neuroprotection from serum deprivation by mu-opioid receptor agonist in differentiated SH-SY5Y cells and primary hippocampal neurons. We found that CDK5 kinase activity decreased following serum deprivation in differentiated SH-SY5Y cells coincident with increased cell loss and activation of caspases cascade activation, which was reversed by opioid antagonist. Overexpression of CDK5 in serum-free medium reversed activation of caspase cascade and augmented DAMGO neuroprotection. Blocking CDK5 activity by pharmacologic inhibitor, roscovitine or overexpression of dominant negative CDK5 augmented activation of cell death markers and diminished mu-opioid receptor agonist protection. Reduction in CDK5 activity corresponded to reduction in protein levels of CDK5 activator p35 during serum deprivation which was also reversed by mu-opioid receptor agonist. Phosphorylation of STAT3 at Serine 727 by CDK5 decreased during serum deprivation, and partly recovered by mu-opioid agonist. PI3K signaling pathway was not required for CDK5-mediated mu-opioid neuroprotection against serum deprivation. These findings indicate that neuroprotection by mu-opioid receptor agonist against serum deprivation is mediated by activation of CDK5 through up-regulation of p35 and phosphorylation of STAT3 by CDK5 may contribute to the neuroprotection.

Animals↗
PubMed2006

Modulating cell adhesion and spreading by control of FnIII7-10 orientation on charged self-assembled monolayers (SAMs) of alkanethiolates.

In this work, we demonstrate that surface charge can be used to modulate cell adhesion/spreading through the control of the orientation of adsorbed FnIII(7-10), which is a cell-adhesive protein containing RGD residues. Carboxylic acid (COOH) and amine (NH(2))-terminated self-assembled monolayers (SAMs) of alkanethiolates were used as model negatively and positively charged surfaces, respectively. The adsorbed amount of FnIII(7-10) is controlled to be equivalent on both SAMs as confirmed by the adsorption isotherms determined using I(125)-radiolabeled FnIII(7-10.) The binding of a monoclonal antibody specific for the cell-binding domain of FnIII(7-10) was measured by surface plasmon resonance (SPR) to evaluate FnIII(7-10) orientations on different SAMs. Results indicate that adsorbed FnIII(7-10) on NH(2)-SAM has an orientation with more cell-binding domains accessible than on COOH-SAM, confirming our predictions from Monte Carlo simulations. Both phase contrast images and Vybrant MTT cell proliferation assays show that the adhesion/spreading of bovine aortic endothelial cells (BAECs) on the NH(2)-SAM is significantly better than that on the COOH-SAM coated with an equivalent amount of FnIII(7-10). These results indicate that surface charge can be used to specifically orient cell adhesive proteins such as FnIII(7-10), thus providing a promising strategy to increase the activity of materials incorporating biological moieties.

Alkanesulfonates↗
PubMed2006

N-acylsulfonamide linker activation by Pd-catalyzed allylation.

N-Acylsulfonamide safety-catch linkers are versatile tools in solid-phase organic synthesis because of their stability. This stability necessitates linker activation prior to compound cleavage. Here, we demonstrate that the N-acylsulfonamide group can react with a pi-allyl palladium complex and that these mild and neutral conditions can be exploited for linker activation. The advantages of this process are illustrated by its use in the efficient synthesis of thioesters. We anticipate that this activation method will extend the utility of the N-acylsulfonamide group. [reaction: see text]

Catalysis↗
PubMed2006

Continuous flow microextraction combined with high-performance liquid chromatography for the analysis of pesticides in natural waters.

Continuous flow microextraction (CFME) combined with high-performance liquid chromatography-ultraviolet (HPLC-UV) detection has been applied to the analysis of five widely used pesticides, simazine, fensulfothion, etridiazole, mepronil and bensulide, present at trace levels in water samples. CFME employs a single organic solvent drop positioned at the tip of a polyether ether ketone (PEEK) tubing, which is immersed in a continuous flowing aqueous sample solution in a 0.5-ml glass chamber. The PEEK tubing acts as the organic drop holder and fluid delivery duct. Analytes are partitioned between the organic drop and the bulk sample solution. Important extraction factors including type of solvent, its volume, sample solution flow rate, extraction time, its pH and addition of salt were investigated. All pesticides exhibit good linearity in the investigated concentration range of 25-250 ng ml(-1) with coefficients of determination (R2) ranging from 0.9879 to 0.9999 under the optimized conditions. Detection limits lower than 4 ng ml(-1) were obtained for all analytes. The method was evaluated by analyzing natural water sample collected from a reservoir in Singapore. This study for the first time demonstrated the compatibility of CFME procedure and HPLC separation.

Chromatography, High Pressure Liquid↗
PubMed2006

Genetic and functional interaction between Ryh1 and Ypt3: two Rab GTPases that function in S. pombe secretory pathway.

We have previously isolated ypt3-i5 mutant and showed that Ypt3 GTPase functions in the fission yeast secretory pathway. Here, the same genetic screen led to the isolation of ryh1-i6, a mutant allele of the ryh1+ gene encoding a homolog of Rab6. The ryh1-i6 mutant showed phenotypes that support its role in retrograde traffic from endosome to the Golgi. Interestingly, ryh1+ gene deletion was synthetically lethal with ypt3-i5 mutation. Consistently, the over-expression of the GDP-conformational mutant, Ryh1T25 N, inhibited the growth of ypt3-i5 mutant but had no effect on that of wild-type cells. Furthermore, the over-expression of the Ryh1T25N mutant inhibited the acid phosphatase glycosylation and exacerbated the cell wall integrity of ypt3-i5 mutant, but had no effect on those of wild-type cells. GFP-Ryh1 and GFP-Ypt3 both localized at the Golgi/endosome, but showed distinct subcellular localizations. The localization of GFP-Ryh1 in ypt3-i5 mutant and that of GFP-Ypt3 in ryh1-i6 mutant were distinct from those in wild-type cells. In addition, Ryh1 as well as Ypt3 were shown to be involved in acid phosphatase secretion. These results suggest that Ryh1 is involved in the secretory pathway and may have a potential overlapping function with Ypt3 in addition to its role in recycling.

Acid Phosphatase↗
PubMed2006

[Influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease].

To investigate the influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease, peripheral blood samples of 20 healthy donors were collected before and after G-CSF mobilization. The whole blood was diluted with IMDM in ratio of 1:1 and then incubated with PMA + ionomycin + monensin at 37 degrees C, 5% CO2 for 4 hours. After being mobilized and stained, the IL-4, IFN-gamma and IL-2 positive cells were counted with three-color flow cytometry. The results showed that before G-CSF mobilization, the percentages of donor's CD3(+)IFN-gamma(+), CD4(+)IFN-gamma(+), CD8(+)IFN-gamma(+) T cells were 3.2% (0% - 45.9%), 1.3% (0% - 23.8%) and 1.5% (0% - 22.2%) respectively. The percentage of above mentioned cells in donor increased to 19.2% (0% - 53.9%), 9.5% (0% - 49.5%), 7.5% (0% - 38.1%) respectively after G-CSF mobilization. The IL-2 positive CD3(+), CD4(+) and CD8(+) T cell percentage in pre-G-CSF mobilized donors was 1.5% (0% - 31%), 0.8% (0% - 30.0%) and 0% (0% - 5.3%) respectively and subsequently increased to 25.7% (0% - 51%), 19.8% (0% - 39.7%), 4.6% (0% - 20.9%) respectively after G-CSF mobilization. The IL-4 positive T subpopulation did not increased significantly after G-CSF mobilization. In the early stage after peripheral blood stem cell transplantation, donor's Tc1 percentage in aGVHD group was significantly higher than that in non-aGVHD group. The morbidity of severe aGVHD in high Tc2 percentage group was significantly lower than that in low Tc2 percentage group. It is concluded that the donor's type I T cells increase after G-CSF mobilization, the Tc1 percentage of G-CSF mobilized donor is correlated with the occurrence of aGVHD in the early stage after HSCT, the percentage of Tc2 in donor is negatively correlated with aGVHD morbidity in recipients.

Adolescent↗
PubMed2006

[Role of alloreactive natural killer cell in mouse MHC haploidentical bone marrow transplantation].

OBJECTIVE: To study the effect of alloreactive natural killer (NK) cells used in conditioning regimen on elimination of recipient-type T cell and granulocyte, reconstitution of hematopoiesis, engraftment and graft-versus-host disease (GVHD) in murine major histocompatibility complex (MHC) haploidentical bone marrow transplantation (BMT). METHODS: The murine model of MHC haploidentical BMT was established by using (C57BL/6 x BALB/c) BCF(1) (H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into 8.5 Gy control group and 7, 6 and 5 Gy experimental groups according to different irradiation dose and different kinds of NK cell treatment. The control group was further subdivided into untreated and BMT groups, while each experimental group was subdivided respectively into untreated group, BMT group, non-allo-reactive NK cells (non-allo NK) group and alloreactive NK cells (allo NK) group. The effect of adding alloreactive NK cell to conditioning regimen was assessed by peripheral white blood cell and platelet counts, recipient type H-2(d+) T cells and granulocytes counts, expression of H-2(d/b+) cells and pathohistological examination. RESULTS: Survival time was (6.00 +/- 0.82) days for 8.5 Gy untreated group, and beyond 60 days for all the other groups. No clinical and histopathological evidence of GVHD was observed in all the groups. The reconstitution of hematopoiesis was faster in allo NK groups than in other groups (P < 0.05). On day 1 after BMT, in allo NK groups with different irradiation dose, bone marrow and spleen recipient type H-2(d+) granulocytes and T cells were significantly decreased compared with identical BMT groups and non-allo NK groups (P < 0.05). The engraftment rates of H-2(d/b+) cells were significantly higher in 7, 6 and 5 Gy allo NK groups than in identical BMT groups and non-allo NK groups (P < 0.05, respectively). CONCLUSIONS: In mouse MHC haploidentical BMT, alloreactive NK cell can eliminate recipient-type T cell and granulocyte, promote reconstitution of hematopoiesis, enhance engraftment while not induce GVHD.

Animals↗
PubMed2006

[Principles and applications of overpressured-layer chromatography].

The principles and applications of overpressured-layer chromatography (OPLC) are reviewed. The instrument and the operation modes of OPLC are introduced, followed by a description of the influence factors of OPLC and how to solve typical problems during the use of OPLC. In addition, the typical applications of OPLC are also summarized.

Chromatography↗
PubMed2005

Improvement on a simplified model for protein folding simulation.

Improvements were made on a simplified protein model--the Ramachandran model-to achieve better computer simulation of protein folding. To check the validity of such improvements, we chose the ultrafast folding protein Engrailed Homeodomain as an example and explored several aspects of its folding. The engrailed homeodomain is a mainly alpha-helical protein of 61 residues from Drosophila melanogaster. We found that the simplified model of Engrailed Homeodomain can fold into a global minimum state with a tertiary structure in good agreement with its native structure.

Amino Acid Sequence↗
PubMed2005

Surface plasmon resonances of silver triangle nanoplates: graphic assignments of resonance modes and linear fittings of resonance peaks.

The extinction spectra of five silver equilateral triangle plates with a fixed thickness of 10 nm and side lengths of 50, 100, 150, 200 ,and 250 nm, respectively, have been simulated by the discrete dipole approximation (DDA) method in which a geometric object of interest is meshed and represented by a lattice of spatial dipoles. Irradiated by an incident plane wave with a given propagation direction and polarization state, each triangle nanoplate presents three surface plasmon resonance (SPR) peaks in the range of 300 to 1200 nm. At a given peak, every complex spatial oscillatory vector derived by DDA (corresponding to a certain dipole in the meshed target) is orthogonally resolved into three basic oscillations. Each basic component can be subsequently expressed by two parameters, amplitude (P) and phase angle (varphi). The distributions of six such physical parameters of all the dipoles in the selected cross plane of the target are illustrated colorfully in plots as a graphic characterization and assignment of the SPR modes. The graphic method is applied to reveal the local fine features of SPR modes. And it provides direct evidence for classifying SPR peaks which belong to different triangle nanoplates and appear at different wavelengths. Three SPR modes are recognized graphically and the wavelengths of SPR peaks are found to have linear relationships with the side lengths of the triangle nanoplates.

Journal Article↗