Biomedical subjects

Xiaoli Wang

Publications and source records attributed to Xiaoli Wang.

At least 19 recordsLinked to original sources

PubMed2026

Splenic extramedullary hematopoiesis in myelofibrosis is shaped by transcriptomic and epigenetic dysregulation.

Myelofibrosis (MF) is a chronic, progressive myeloproliferative neoplasm characterized by bone marrow fibrosis, ineffective blood cell production, and neoplastic extramedullary hematopoiesis (EMH) occurring primarily within the spleen. To explore the molecular mechanisms underlying splenic EMH, we performed single-cell transcriptional and chromatin profiling of cells from MF spleens that had been surgically removed. We demonstrate significant expansion of hematopoietic stem and progenitor cells, coupled with aberrant differentiation toward the erythroid and megakaryocytic lineages, associated with a significant enrichment of inflammatory pathways with enhanced NF-κB signaling and IFN responses, as well as dysregulation of the inferred function of differentiation-defining transcription factors. Finally, we report a significant remodeling of the immune microenvironment in MF spleens, characterized by emergence of dysfunctional T cell subsets and inflammatory memory B cells, suggesting the concomitant establishment of a pro-inflammatory and immune-tolerant tumor microenvironment within the spleen that influences hematopoietic cell differentiation and impairs tumor immune surveillance.

Primary Myelofibrosis↗

PubMed2006

High content of resveratrol in lettuce transformed with a stilbene synthase gene of Parthenocissus henryana.

Resveratrol (trans-3,5,4'-trihydroxystilbene) is a plant phytoalexin which has positive effects on human health. Stilbene synthase (STS) is a key enzyme involved in resveratrol biosynthesis. To construct a vector for STS expression in lettuce plant, a cDNA-encoding STS of Parthenocissus henryana was fused to the Cauliflower mosaic virus (CaMV) 35S promoter, and the bar gene was used as a selective marker gene. To increase the expression of STS, the expression cassette was flanked by MARs. In transgenic lettuce plants, an additional compound was identified as resveratrol by HPLC and ESI-MS. Quantitative analysis showed that the average content of resveratrol reached 56.40 +/- 5.52 microg/g leaf fresh weight, which was comparable to the amount in grape skin. Anticancer assay in HeLa cells revealed that apoptosis was induced by 200 microM of resveratrol extracted from transgenic lettuce.

Acyltransferases↗

PubMed2006

Evaluation of the role of sympathetic denervation on hepatic function.

It is acknowledged that autonomic nerves play an important role on liver function. Sympathetic nerve is the main component of them. This study is to evaluate the effects of sympathetic denervation of the liver on liver function in the normal and chemically injured liver, and its influence on liver regeneration. Eighty healthy male Wistar rats were divided randomly into four groups: Sham group, carbon tetrachloride group (CCL4), 6-hydroxydopamine group (6-OHDA), and CCL4+6-OHDA group. Chemical denervation model was made by injection of 6-OHDA (2ml, 100mg/l) through the mesenteric vein of jejunum loop. Acute liver injury model was established by using CCL4. Blood chemistry, ATP, arterial ketone body ratio (AKBR) and indocyanine green (ICG(15)) were measured in each group after administration of sympathetic denervation or/and acute liver injury. Liver regeneration was assessed with hepatic mass index (HMI), rate of liver regeneration (RLR), mitotic index (MI) and the rates of DNA synthesis under sympathetic denervation. Chemical denervation resulted in significant changes of liver function tests under acute liver injury, and had beneficial effects on protein anabolism, metabolism of bilirubin and energy, and ICG excretion, meanwhile, alleviated low potassium in serum. However, sympathetic denervation only had no effects on liver function tests. It decreased significantly in sympathetic denervation group for HMI, RLR, MI and the rate of DNA synthesis with 3H-TdR (P<0.01). It is concluded that sympathetic denervation can alleviate liver injury by CCL4, impair liver regeneration, but has no effects on liver function tests under normal.

Journal Article↗

PubMed2006

Lin(-)CD34(-) bone marrow cells from adult mice can differentiate into neural-like cells.

Numerous studies have shown that some populations of bone marrow cells (BMCs) have the capacity to differentiate into neural cells, which is useful for repairing brain lesions. In this paper, we analyze neural differentiation features of lineage-negative/CD34-negative (Lin(-)CD34(-)) cells in the bone marrow of adult mice. The population of Lin(-)CD34(-) in BMCs was isolated by magnetic bead sorting and fluorescence-activated cell sorter (FACS) using specific lineage (CD4, CD8a, CD11b, CD45R, Gr-1 and TER-119) antibodies and CD34 antibody. First, we cultured Lin(-)CD34(-) BMCs in the presence of RNIF: vitamin A derivative retinoic acid (RA) and neural-inducing factors (platelet-derived growth factor BB (PDGF-BB), epidermal growth factor (EGF) and fibroblast growth factor-basic (FGF-b)). Analyses of RT-PCR and immunocytochemistry indicated that RNIF-treated Lin(-)CD34(-) BMCs expressed neural phenotypes as well as neurogenic transcription factors. When we implanted the Lin(-)CD34(-) BMCs isolated from enhanced green fluorescent protein (eGFP) transgenic mice into the subventricular zone (SVZ) of postnatal mice, eGFP-positive cells survived 3 weeks after the injection in the various brain regions, some of which expressed the neural phenotypes. Our data suggest that certain subsets in the CD34(-) populations of adult bone marrow could have the capacity to differentiate into neural cells in a suitable environment.

Animals↗

PubMed2006

An ultrathin self-humidifying membrane for PEM fuel cell application: fabrication, characterization, and experimental analysis.

An ultrathin poly(tetrafluoroethylene) (PTFE)-reinforced multilayer self-humidifying composite membrane (20 microm, thick) is developed. The membrane is composed of Nafion-impregnated porous PTFE composite as the central layer, and SiO2 supported nanosized Pt particles (Pt-SiO2) imbedded into the Nafion as the two side layers. The proton exchange membrane (PEM) fuel cell employing the self-humidifying membrane (Pt-SiO2/NP) turns out a peak power density of 1.40 W cm(-2) and an open circuit voltage (OCV) of 1.032 V under dry H2/O2 condition. The excellent performance is attributed to the combined result of both the accelerated water back-diffusion in the thin membrane and the adsorbing/releasing water properties of the Pt-SiO2 catalyst in the side layers. Moreover, the inclusion of the hygroscopic Pt-SiO2 catalyst inside the membrane results in an enhanced anode self-humidification capability and also the decreased cathode polarization (accordingly an improved cell OCV). Several techniques, such as transmission electronic microscopy, scanning electronic microscopy, energy dispersive spectroscopy, thermal analysis and electrochemical impedance spectroscopy etc., are employed to characterize the Pt-SiO2/NP membrane. The results are discussed in comparison with the plain Nafion/PTFE membrane (NP). It is established that the reverse net water drag (from the cathode to the anode) across the Pt-SiO2/NP membrane reaches 0.16 H2O/H+. This implies a good hydration of the Pt-SiO2/NP membrane and thus ensures an excellent PEM fuel cell performance under self-humidification operation.

Electric Power Supplies↗

PubMed2006

Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms.

We have reported that epoxyeicosatrienoic acids (EETs), the cytochrome P450 (CYP) epoxygenase metabolites of arachidonic acid (AA), are potent sarcolemmal ATP-sensitive K+ (KATP) channel activators. However, activation of cardiac and vascular KATP channels by endogenously produced EETs under physiological intracellular conditions has not been demonstrated and direct comparison of the mechanisms whereby EETs activate the KATP channels in cardiac myocytes versus vascular smooth muscle cells has not been made. In this study, we examined the effects of AA on KATP channels in freshly isolated cardiac myocytes from rats, wild-type (WT) and transgenic mice overexpressing CYP2J2 cDNA, and mesenteric arterial smooth muscle cells from rats. We also compared the activation of cardiac and vascular KATP channels by extracellularly and intracellularly applied 11,12-EET. We found that 1 microm AA enhanced KATP channel activities in both cardiac and vascular smooth muscle cells, and the AA effects were inhibited by preincubation with CYP epoxygenase inhibitors. Baseline cardiac KATP current densities in CYP2J2 transgenic mice were 190% higher than those of WT mice, and both were reduced to similar levels by CYP epoxygenase inhibition. Western blot analysis showed that expression of Kir6.2 and SUR2A was similar between WT and CYP2J2 transgenic hearts. 11,12-EET (5 microm) applied intracellularly enhanced the KATP currents by 850% in cardiac myocytes, but had no effect in vascular smooth muscle cells. In contrast, 11,12-EET (5 microm) applied extracellularly increased KATP currents by 520% in mesenteric arterial smooth muscle cells, but by only 209% in cardiac myocytes. Preincubation with 100 microm m-iodobenzylguanidine or 5 microm myristoylated PKI amide did not alter the activation of cardiac KATP channels by 5 microm 11,12-EET, but significantly inhibited activation of vascular KATP channels. Moreover, EET only enhanced the inward component of cardiac KATP currents, but activated both the inward and outward components of vascular KATP currents. Our results indicate that endogenously derived CYP metabolites of AA potently activate cardiac and vascular KATP channels. EETs regulate cardiac electrophysiology and vascular tone by KATP channel activation, albeit through different mechanisms: the cardiac KATP channels are directly activated by EETs, whereas activation of the vascular KATP channels by EETs is protein kinase A dependent.

8,11,14-Eicosatrienoic Acid↗

PubMed2006

A graphical method for understanding the kinetics of peak capacity production in gradient elution liquid chromatography.

A novel graphical method for assessing the compromise between conditional peak capacity and separation speed for packed bed columns under gradient conditions has been developed and applied to the separation of peptides. This approach is analogous to and complements the conventional "Poppe plot" used to study plate count in isocratic separations. The use of the new plot can assist the design of appropriate column formats (e.g. particle size and column length) for both dimensions in gradient elution two-dimensional liquid chromatography (2DLC). Particularly for the second dimension of 2DLC, we find that smaller particles provide faster separations even though fast separations based on particles smaller than 2 microm are practically limited by the required miniscule column length. We also find that high temperatures strongly enhance the kinetics of peak capacity production whereas higher pressures help achieve larger absolute peak capacities albeit at the cost of longer analysis time.

Chromatography, Liquid↗

PubMed2006

Peak capacity optimization of peptide separations in reversed-phase gradient elution chromatography: fixed column format.

The optimization of peak capacity in gradient elution RPLC is essential for the separation of multicomponent samples such as those encountered in proteomic research. In this work, we study the effect of gradient time (tG), flow rate (F), temperature (T), and final eluent strength (phi(final)) on the peak capacity of separations of peptides that are representative of the range in peptides found in a tryptic digest. We find that there are very strong interactions between the individual variables (e.g., flow rate and gradient time) which make the optimization quite complicated. On a given column, one should first set the gradient time to the longest tolerable and then set the temperature to the highest achievable with the instrument. Next, the flow rate should be optimized using a reasonable but arbitrary value of phi(final). Last, the final eluent strength should be adjusted so that the last solute elutes as close as possible to the gradient time. We also develop an easily implemented, highly efficient, and effective Monte Carlo search strategy to simultaneously optimize all the variables. We find that gradient steepness is an important parameter that influences peak capacity and an optimum range of gradient steepness exists in which the peak capacity is maximized.

Animals↗

PubMed2006

Synthesis and structure-activity relationship exploration of carbon-supported PtRuNi nanocomposite as a CO-tolerant electrocatalyst for proton exchange membrane fuel cells.

A carbon-supported PtRuNi nanocomposite is synthesized via a microwave-irradiated polyol plus annealing synthesis strategy. The catalyst is characterized by transmission electron microscopy, powder X-ray diffraction, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy. The data are discussed with respect to those for the carbon-supported PtRu nanocomposite prepared following the same way. The characterizations show that the inclusion of Ni in the PtRu system has only a small effect on the particle size, the structure, and the compositional homogeneity. CO-stripping voltammetry and measurements on the single proton exchange membrane fuel cells show that the PtRuNi/C catalyst has an improved activity for CO(ads) electro-oxidation. An accelerated durability test on the catalyst exhibits insignificant loss of activity in acidic media. On the basis of the exploration of the structure-activity relationship, a mechanism for the improved performance of the catalyst is proposed. It is suggested that the improved CO-tolerant performance of the PtRuNi/C nanocomposite should be related to the hydrogen spillover on the catalyst surface, the enhanced oxidation of CO(ads) by nickel hydroxides, and the high proton and electronic conductivity of the hydroxides. The nickel hydroxide passivated surface and/or anchoring of metallic nickel in the platinum lattice may contribute to the durability of the catalyst in acid solution.

Journal Article↗

PubMed2006

Cu and Zn adsorption onto non-residual and residual components in the natural surface coatings samples (NSCSs) in the Songhua River, China.

Natural surface coatings samples (NSCSs) from the surface of river shingles were employed to investigate the roles of non-residual and residual components of the NSCSs in controlling Cu and Zn adsorption via the selective extraction techniques and statistical analysis. The results indicate that the greatest contribution to metals adsorption on a molar basis was from Mn oxides in the non-residual fraction. Metals adsorption capacities of Mn oxides exceeded those of Fe oxides by one order of magnitude, fewer roles were found attributing to adsorption by organic materials (OM), and the estimated contribution of the residual fraction to metals adsorption was insignificant. These results implied that Mn oxides were the most important component in controlling heavy metals in aquatic environments. Experiments with Cu and Zn adsorption measured together showed that Cu severely interfered with Zn adsorption to the NSCSs and vice versa under the conditions of the two coexisted ions adsorption.

Adsorption↗

PubMed2006

The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins.

Ubiquitin E3 ligases are important cellular components for endoplasmic reticulum (ER)-associated degradation due to their role in substrate-specific ubiquitination, which is required for retrotranslocation (dislocation) of most unwanted proteins from the ER to the cytosol for proteasome degradation. However, our understanding of the molecular mechanisms of how E3 ligases confer substrate-specific recognition, and their role in substrate retrotranslocation is limited especially in mammalian cells. mK3 is a type III ER membrane protein encoded by murine gamma herpesvirus 68. As conferred by its N-terminal RING-CH domain, mK3 has E3 ubiquitin ligase activity. In its role as an immune evasion protein, mK3 specifically targets nascent major histocompatibility complex class I heavy chains (HC) for rapid degradation. The mechanism by which mK3 extracts HC from the ER membrane into the cytosol for proteasome-mediated degradation is unknown. Evidence is presented here that HC down-regulation by mK3 is dependent on the p97 AAA-ATPase. By contrast, the kK5 protein of Kaposi's sarcoma-associated herpesvirus is p97-independent despite the fact that it is highly homologous to mK3. mK3 protein was also found in physical association with Derlin1, an ER protein recently implicated in the retrotranslocation of HC by immune evasion protein US11, but not US2, of human cytomegalovirus. The mechanistic implications of these findings are discussed.

Adenosine Triphosphatases↗

PubMed2006

High-throughput assay of DNA methylation based on methylation-specific primer and SAGE.

Mapping of genomic DNA methylation is a dispensable part of functional genome. We have developed a novel method based on methylation-specific primer and serial analysis of gene expression, called MSP-SAGE, with potential of high-throughput quantification of genomic DNA methylation. We used a 6-mer methylation-specific primer to extend the methylated CpG sequences other than non-methylated CpG sequences. The 17 bp tags contained methylated CpG sequence, which were obtained from extended methylation sequence by digestion of restriction endonuclease, and then the tags were concatenated and cloned for sequencing. We can identify the locations of methylation according to the sequences of tags and quantify the methylation status from the frequency of the tags. MSP-SAGE has a good linearity in a broad methylation range from 5% to 100% with good accuracy and high precision. The proof-of-principle study shows that MSP-SAGE is a reliable high-throughput assay for quantification of DNA methylation.

Alleles↗

PubMed2006

A practical approach to maximizing peak capacity by using long columns packed with pellicular stationary phases for proteomic research.

Maximization of peak capacity is a very important step in developing one-dimensional separations of complex samples. In recent work, it was shown that the use of small particles in combination with the new technique of ultrahigh pressure liquid chromatography (UHPLC) was able to generate very high peak capacities. Here we show the ability of conventional HPLC instrumentation to give comparable peak capacities to those obtained in UHPLC for the important case of complex mixtures of peptides but at much lower pressures by using a 60 cm long set of columns packed with 5 microm pellicular (superficially porous) particles. We first show, in complete agreement with the well known results of the theory of isocratic separations that, when time is not limiting, the best peak capacities in gradient elution chromatography are obtained by using large particles and the longest column that can be operated at the pump's pressure limit. Two different types of 5 microm particles (superficially porous and totally porous) were compared for their efficiency in gradient chromatography of peptides. We find that the pellicular material gave about 50% higher peak capacity compared to the analogous porous material. A 60 cm column set packed with pellicular particles was made by connecting short columns in series; a peak capacity of about 460 was obtained in 4 h at room temperature. Increasing the column temperature to 70 degrees C reduced the analysis time to 2 h and further increased the peak capacity to more than 500. The number of peaks observed in the separation of bovine serum albumin tryptic peptides was greatly increased and the separation quality was significantly improved.

Chromatography, High Pressure Liquid↗

PubMed2006

Aging-related changes of microglia and astrocytes in hypothalamus after intraperitoneal injection of hypertonic saline in rats.

To examine the aging-related changes of microglia and astrocytes in hypothalamus of rats after intraperitoneal injection of hypertonic saline in rats, old- and young-aged rats were injected with hypertonic saline solution into peritoneal cavity. Lectin histochemical techniques using Ricinus communis agglutinin-1 (RCA-1) and immunocytochemical method employing antibody against glial fibrillary acidic protein (GFAP) were used to demonstrate microglia and astrocytes in the hypothalamus of the rats, and the positively-stained cells were analyzed by computer-assisted image analysis system. Our results showed that the numbers of microglia and astrocytes were significantly increased in the hypothalamus of old-aged rats. After intraperitoneal injection of hypertonic saline, the number of microglia was significantly decreased in the hypothalamus of both young- and old-aged groups. After introperitoneal injection of hypertonic saline, the number of GFAP positive cells was significantly increased in the hypothalamus of young rats, but the number of GFAP positive cells did not show significant change in the hypothalamus of old rats. It is concluded that in the hypothalamus of old-aged rats, the increase of microglia may be related with the aging or degeneration of neurons, and the increase of astrocytes may provide more nourishment required by the aged neurons. The microglia and astrocytes in the hypothalamus of the two group rats may be affected by hypertonic saline, and the response of these cells to the stimuli is characterized by some aging-related changes.

Aging↗

PubMed2006

Expression of Pdx-1 in bone marrow mesenchymal stem cells promotes differentiation of islet-like cells in vitro.

Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and multi-directional differentiation. Recent reports showed that BMSCs could differentiate into endocrine cells of pancreas. However, the differentiation is not efficient enough to produce insulin-producing cells for the future therapeutic use. Pdx-1 is a crucial regulator for pancreatic development. Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro. The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation in vitro. The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23% +/- 2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1-BMSCs (7.23% +/- 1.56% and 4.08% +/- 2.69% respectively) by flow cytometry. Immunocytochemical examination also testified the expression of multiple beta-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. The results also revealed that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1-BMSCs, which was confirmed by Western blotting analysis and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5 mmol/L and 25 mmol/L glocuse was (56.61 +/- 4.82) microU/mL and (115.29 +/- 2.56) microU/mL respectively, which were much higher than those from Pdx-1-BMSCs ((25.53 +/- 6.49) microU/mL and (53.26 +/- 7.56) microU/mL respectively). Grafted animals were able to maintain their body weight and survive for relatively longer periods of time than hyperglycemic sham-grafted controls, which demonstrated an overall beneficial effect of the grafted cells on the health of the animals. These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use in diabetic patients.

Animals↗

PubMed2006

The effect of occupational exposure to metals on the nervous system function in welders.

We explored the relationship between metals exposure and nervous impairment in welders. The metals exposure of 82 welders and 51 operators were evaluated for blood Pb, Cd and Mn by atomic absorption spectrometry, and the nervous system impairment was evaluated with the neurobehavioral core test battery and electromyography. Pb (geometric mean: 117.31 mug/L; range: 0.5-327.6 mug/L) and Cd (geometric mean: 3.54 mug/L; range: 0.2-12.5 mug/L) in welders were significantly higher than those in operators. Welders had higher prevalence of nervous system symptoms and worse standard scores of 8 items such as depression-dejection than operators. Significant difference of nervous performance in welders only existed in different concentration groups of Pb and Mn. The performances of fatigue-inertia and some others had negative correlations with Pb and digit span with Mn. Therefore, the nervous system impairment in welders could be attributed to occupational exposure of Pb and Mn, but not Cd, concomitantly.

Adult↗

PubMed2005

Characterization of mesenchymal stem cells isolated from mouse fetal bone marrow.

Mesenchymal stem cells (MSCs) are defined as cells that can differentiate into multiple mesenchymal lineage cells. MSCs have some features (surface molecules and cytokine production, etc.) common to so-called traditional bone marrow (BM) stromal cells, which have the capacity to support hemopoiesis. In the present study, we isolated murine MSCs (mMSCs) from the fetal BM using an anti-PA6 monoclonal antibody (mAb) that is specific for bone marrow stromal cells. The mMSCs, called FMS/PA6-P cells, are adherent, fibroblastic, and extensively expanded and have the ability to differentiate not only into osteoblasts and adipocytes but also into vascular endothelial cells. The FMS/PA6-P cells produce a broad spectrum of cytokines and growth factors closely related to hemopoiesis and show good hemopoiesis-supporting capacity both in vivo and in vitro, suggesting that they are a component of the hemopoietic stem cell niche in vivo. Interestingly, although the FMS/PA6-P cells express a high level of the PA6 molecule, which is reactive with anti-PA6 mAb, they gradually lose their ability to express this molecule during the course of differentiation into osteoblasts and adipocytes, indicating that the PA6 molecule might serve as a novel marker of mMSCs.

Adipocytes↗

PubMed2005

Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells.

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.

Amino Acids↗