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Biomedical subjects

Yang Xia

Publications and source records attributed to Yang Xia.

At least 19 recordsLinked to original sources

Tropane alkaloids production in transgenic Hyoscyamus niger hairy root cultures over-expressing putrescine N-methyltransferase is methyl jasmonate-dependent.

The cDNA from Nicotiana tabacum encoding Putrescine N-methyltransferase (PMT), which catalyzes the first committed step in the biosynthesis of tropane alkaloids, has been introduced into the genome of a scopolamine-producing Hyoscyamus niger mediated by the disarmed Agrobacterium tumefaciens strain C58C1, which also carries Agrobacterium rhizogenes Ri plasmid pRiA4, and expressed under the control of the CaMV 35S promoter. Hairy root lines transformed with pmt presented fivefold higher PMT activity than the control, and the methylputrescine (MPUT) levels of the resulting engineered hairy roots increased four to fivefold compared to the control and wild-type roots, but there was no significant increase in tropane alkaloids. However, after methyl jasmonate (MeJA) treatment, a considerable increase of PMTase and endogenous H6Hase as well as an increase in scopolamine content was found either in the transgenic hairy roots or the control. The results indicate that hairy root lines over-expressing pmt have a high capacity to synthesize MPUT, whereas their ability to convert hyoscyamine into scopolamine is very limited. Exposure to MeJA strongly stimulated both polyamine and tropane biosynthesis pathways and elicitation led to more or less enhanced production simultaneously.

Acetates↗

Rapidly growing collagenomas in multiple endocrine neoplasia type I.

Patients with multiple endocrine neoplasia type I (MEN-I) frequently develop skin lesions including collagenomas, angiofibromas, and lipomas. We report a patient with MEN-I who exhibited rapid growth of multiple collagenomas after pancreatic enucleation of a vasoactive intestinal peptide-secreting tumor (VIPoma) and excision of multiple pancreatic masses. Five of the collagenomas were protuberant, with the bulk of the lesion protruding above the skin. Histologic analysis of the collagenomas revealed broad collagen bundles in a haphazard arrangement and decreased elastic fibers. Rapid growth of protuberant collagenomas appears to be unusual in MEN-I, but we suggest that MEN-I be considered in patients with apparent eruptive collagenoma.

Adult↗

Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy.

Maternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular endothelial growth factor and placental growth factor. Angiotensin II (Ang II) is a potent vasoconstrictor that increases concomitant with sFlt-1 during pregnancy. Therefore, we speculated that Ang II may promote the expression of sFlt-1 in pregnancy. Here we report that infusion of Ang II significantly increases circulating levels of sFlt-1 in pregnant mice, thereby demonstrating that Ang II is a regulator of sFlt-1 secretion in vivo. Furthermore, Ang II stimulated sFlt-1 production in a dose- and time-dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells, suggesting that trophoblasts are the primary source of sFlt-1 during pregnancy. As expected, Ang II-induced sFlt-1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation. In vitro and in vivo studies with losartan, small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II-mediated sFlt-1 release was via Ang II type 1 receptor activation and calcineurin signaling, respectively. These findings reveal a previously unrecognized regulatory role for Ang II on sFlt-1 expression in murine and human pregnancy and suggest that elevated sFlt-1 levels in preeclampsia may be caused by a dysregulation of the local renin/angiotensin system.

Angiotensin II↗

Recent developments and future prospects of Vitreoscilla hemoglobin application in metabolic engineering.

In hypoxic conditions, bacteria express a kind of hemoglobin, which is proposed to enhance respiration and energy metabolism by promoting oxygen delivery. Bacteria hemoglobin from Vitreoscilla stercoraria - Vitreoscilla hemoglobin (VHb), when expressed in various hosts in oxygen-limited conditions, has been shown to improve growth, protein secretion, metabolite productivity and stress resistance of hosts, thus rendering the protein promising in metabolic engineering, especially in plant metabolism optimization. In this review, many well-studies areas are presented to illustrate the potential of VHb application in biotechnology industry, to discuss the cellular mechanisms of VHb function and to show the wide variety of approaches taken within the field.

Bacteria↗

Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: co-operation with Src tyrosine kinase.

OBJECTIVE: To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes. METHODS: iNOS expression was studied in isolated neonatal rat ventricular myocyte cultures in response to bacterial lipopolysaccharide (LPS) or following transfection with constitutively active calcineurin or Src and in hearts isolated from wild-type or calcineruin Abeta knockout mice. Cell injury in response to simulated ischemia-reperfusion was studied following overexpression of active calcineurin. Regulation of the iNOS gene promoter by calcineurin was studied using promoter-luciferase reporter and chromatin immunoprecipitation assays. RESULTS: Overexpression of constitutively active Src co-operated with [Ca2+]c elevation to induce iNOS expression, and LPS-induced iNOS expression was abrogated by pharmacological inhibition of calcineurin or tyrosine kinase. LPS also induced tyrosine kinase-dependent but calcineurin-independent phosphorylation of Src Tyr418. LPS induced myocardial iNOS expression in wild-type but not calcineurin Abeta knockout mice. Overexpression of constitutively active calcinuerin in isolated cardiomyocytes caused dephosphorylation and nuclear accumulation of the c1 isoform of nuclear factor of activated T-cells (NFATc1), induced strong iNOS expression, and induced NOS-dependent protection against simulated ischemia-reperfusion prior to cardiomyocyte hypertrophy. Co-transfection of a mouse iNOS promoter-luciferase reporter in combination with active calcineurin and wild-type or dominant negative Src confirmed that constitutive activation of calcineurin was sufficient for transactivation. Chromatin immunoprecipitation confirmed calcineurin-dependent in vivo binding of NFATc1 to consensus sites within the iNOS promoter. CONCLUSIONS: These results support a cardioprotective role for calcineurin mediated by NFAT-dependent induction of iNOS expression and co-operativity between calcineurin and Src.

Animals↗

Protein kinase-mediated regulation of calcineurin through the phosphorylation of modulatory calcineurin-interacting protein 1.

Calcineurin is a serine/threonine protein phosphatase that plays a critical role in many physiologic processes such as T-cell activation, skeletal myocyte differentiation, and cardiac hypertrophy. We previously showed that active MEKK3 is capable of stimulating calcineurin/nuclear factor of activated T-cells (NFAT) signaling in cardiac myocytes through phosphorylation of modulatory calcineurin-interacting protein 1 (MCIP1). However, the protein kinases that function downstream of MEKK3 to mediate MCIP1 phosphorylation and the mechanism of MCIP1-mediated calcineurin regulation have not been defined. Here, we show that MEK5 and big MAP kinase 1 (BMK1) function downstream of MEKK3 in a signaling cascade that induces calcineurin activity through phosphorylation of MCIP1. Genetic studies showed that BMK1-deficient mouse lung fibroblasts failed to mediate MCIP1 phosphorylation and activate calcineurin/NFAT in response to angiotensin II, a potent NFAT activator. Conversely, restoring BMK1 to the deficient cells restored angiotensin II-mediated calcineurin/NFAT activation. Thus, using BMK1-deficient mouse lung fibroblast cells, we provided the genetic evidence that BMK1 is required for angiotensin II-mediated calcineurin/NFAT activation through MICP1 phosphorylation. Finally, we discovered that phosphorylated MCIP1 dissociates from calcineurin and binds with 14-3-3, thereby relieving its inhibitory effect on calcineurin activity. In summary, our findings reveal a previously unrecognized essential regulatory role of mitogen-activated protein kinase signaling in calcineurin activation through the reversible phosphorylation of a calcineurin-interacting protein, MCIP1.

14-3-3 Proteins↗

[A preliminary study in establishment of mice model of experimental uveal melanoma].

OBJECTIVE: To explore the methods to establish a nude mice model of experimental uveal melanoma by the implantation the primary cultured cells into anterior chamber or subcutaneous injection. METHODS: 35 nude mice, which applied with the SPF grade standard by national healthy department, were divided into 3 groups: anterior chamber group (15), subcutaneous A group (10) and subcutaneous B group (10), respectively. (2 - 3) x 10(5) melanoma cells were inoculated into the anterior chamber of each nude mouse, while 2 x 10(6) cells were inoculated into every subcutaneous of the hind legs in A group. Besides this, the fresh mass of the tumor come from enucleated eye were transplanted into every subcutaneous of the hind legs in B group. Then the condition of transplanted tumor were observed under the slit lamp and naked eye, all nude mice were followed for 3 months the rates of tumor induction were compared. RESULTS: The results of the rates of tumor induction in the 3 groups were 7 (46.6%) of 15, 2 (20%) of 10 and 0 of 10, respectively. The discrepancy were of significance (chi(2) = 7.080, P = 0.029). CONCLUSIONS: Uveal melanoma can be induced successfully by inoculation the primary cultured human uveal melanoma cells into anterior chamber or subcutaneous in nude mice. The results suggest that the ration of the tumor growth is higher in subcutaneous mass transplant than any other groups.

Adult↗

[Surface modification and microstructure of single-walled carbon nanotubes for dental composite resin].

In order to improve its dispersion condition in dental composite resin and enhance its interaction with the matrix, single-walled carbon nanotubes(SWNTs) were refluxed and oxidized, then treated by APTE. Their outer surface were coated by nano-SiO2 particles using sol-gel process, then further treated by organosilanes ATES. IR and TEM were used to analyze modification results. TEM pictures showed nano-particles were on the surface of SWNTs; IR showed characteristic adsorbing bands of SiO2. Composite resin specimen with modified SWNTs was prepared and examined by TEM. SWNTs were detected in composite resin matrix among other inorganic fillers.

Composite Resins↗

Analysis of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine by extraction on a molecularly imprinted polymer column and liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is present in the urine of tobacco users and, at lower concentrations, in the urine of nonsmokers exposed to secondhand smoke. NNAL is a valuable biomarker of human exposure to the carcinogenic nitrosamines in tobacco and tobacco smoke, but its presence at low concentrations in urine requires sensitive and often complex analytic procedures. In this report, we describe the development of an efficient method for the analysis of NNAL in human urine using liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/MS/MS) combined with a novel sample cleanup based on a molecularly imprinted polymer (MIP) column developed specifically for this assay. Our results suggest that this combination of MIP column extraction and LC/MS/MS can provide a sensitive and relatively simple analytical method suitable for application to epidemiologic investigations of health risks associated with the exposure to tobacco smoke or SHS in both smokers and nonsmokers.

Calibration↗

The essential role of MEKK3 signaling in angiotensin II-induced calcineurin/nuclear factor of activated T-cells activation.

Calcineurin is a serine/threonine protein phosphatase that plays a critical role in many physiologic processes, such as T-cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. We determined that active MEKK3 was capable of activating calcineurin/nuclear factor of activated T-cells (NFAT) signaling in cardiac myocytes and reprogramming cardiac gene expression. In contrast, small interference RNA directed against MEKK3 and a dominant negative form of MEKK3 caused the reduction of NFAT activation in response to angiotensin II in cardiac myocytes. Genetic studies showed that MEKK3-deficient mouse embryo fibroblasts failed to activate calcineurin/NFAT in response to angiotensin II, a potent NFAT activator. Conversely, restoring MEKK3 to the MEKK3-deficient cells restored angiotensin II-mediated calcineurin/NFAT activation. We determined that angiotensin II induced MEKK3 phosphorylation. Thus, MEKK3 functions downstream of the AT1 receptor and is essential for calcineurin/NFAT activation. Finally, we determined that MEKK3-mediated activation of calcineurin/NFAT signaling was associated with the phosphorylation of modulatory calcineurin-interacting protein 1 at Ser(108) and Ser(112). Taken together, our studies reveal a previously unrecognized novel essential regulatory role of MEKK3 signaling in calcineurin/NFAT activation.

Angiotensin II↗

Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice.

Pulmonary fibrosis is a common feature of numerous lung disorders, including interstitial lung diseases, asthma, and chronic obstructive pulmonary disease. Despite the prevalence of pulmonary fibrosis, the molecular mechanisms governing inflammatory and fibroproliferative aspects of the disorder are not clear. Adenosine is a purine-signaling nucleoside that is generated in excess during cellular stress and damage. This signaling molecule has been implicated in the regulation of features of chronic lung disease; however, the impact of adenosine on pulmonary fibrosis is not well understood. The goal of this study was to explore the impact of endogenous adenosine elevations on pulmonary fibrosis. To accomplish this, adenosine deaminase (ADA)-deficient mice were treated with various levels of ADA enzyme replacement therapy to regulate endogenous adenosine levels in the lung. Maintaining ADA-deficient mice on low dosages of ADA enzyme therapy led to chronic elevations in lung adenosine levels that were associated with pulmonary inflammation, expression of profibrotic molecules, collagen deposition, and extreme alteration in airway structure. These features could be blocked by preventing elevations in lung adenosine. Furthermore, lowering lung adenosine levels after the establishment of pulmonary fibrosis resulted in a resolution of fibrosis. These findings demonstrate that chronic adenosine elevations are associated with pulmonary fibrosis in ADA-deficient mice and suggest that the adenosine functions as a profibrotic signal in the lung.

Adenosine↗

Modifications of orientational dependence of microscopic magnetic resonance imaging T(2) anisotropy in compressed articular cartilage.

PURPOSE: To investigate the compression-induced changes in the orientational characteristics in T(2) anisotropy of articular cartilage using microscopic magnetic resonance imaging (microMRI). MATERIALS AND METHODS: Six beagle specimens were subjected to various levels of strain (0% to 27%) and were imaged at a minimum of two orientations (0 degrees and 55 degrees ). Two specimens at 14% and 27% strain were imaged at every 5 degrees increment over the first quadrant of the angular space. Quantitative two-dimensional T(2) images and three-dimensional T(2) anisotropy maps of cartilage were constructed at a 19.8-microm in-depth resolution. RESULTS: The load-induced laminar appearance of cartilage at the magic angle became more distinct as the strain level increased. T(2) anisotropy maps of cartilage at 14% and 27% strain exhibited load-induced modifications in the collagen fibril ultrastructure, with a new peak toward the cartilage-bone interface and alterations to orientational dependence of T(2) anisotropy. CONCLUSION: Distinct alternations in the orientational dependence of microMRI T(2) anisotropy reflect the organizational modification of the collagen matrix due to external loading. This approach could become useful in detecting changes in cartilage's macromolecular structure due to injury or diseases.

Algorithms↗

Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion.

BACKGROUND: Preeclampsia affects 3-5% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT(1)) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT(1) receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (Pai-1) secretion in human mesangial cells. METHODS: The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT(1) receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT(1) receptor activation. RESULTS: The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT(1) receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT(1) receptor was stimulated by AT1-AA. CONCLUSIONS: Our findings suggest that a maternal autoantibody with the ability to activate AT(1) receptors may account for the development of renal damage seen in preeclamptic patients.

Animals↗

Orientational dependence of trimethyl ammonium signal in human muscles by (1)H magnetic resonance spectroscopic imaging.

(1)H magnetic resonance spectroscopic imaging (MRSI) was used to investigate the effect of orientation on spectral characteristics of trimethyl ammonium (TMA) in human muscle at rest. Four different muscles in the healthy calf were studied: soleus, gastrocnemius, tibial posterior and anterior. The data demonstrate that muscle orientation can profoundly change apparent spectral characteristics of proton metabolites. In particular, muscle orientation can cause concerted changes in the spectral pattern of TMA/methyl (tCr) and methylene (Cr2) protons of creatine for a given muscle, a switch of TMA/tCr spectral patterns among different muscles and changes in the T(2) of TMA. A significant correlation was detected between TMA/tCr peaks and the Cr2 peak splitting (r=.62, P<.001). In vivo (1)H MRSI has the potential to simultaneously evaluate the orientation of muscle fibers and biochemical changes induced by a disease process or physiological activity.

Creatine↗

Acupuncture for treatment of climacteric syndrome--a report of 35 cases.

OBJECTIVE: To evaluate the effects of acupuncture for treatment of climacteric syndrome. METHODS: The 65 cases in this series were randomly assigned to the acupuncture group (N=35) and the control group (N=30), with the former treated by acupuncture and the latter by medication respectively. The therapeutic effects were evaluated by means of the clinical outcome, improvement in the symptom scores and the results of radioimmunoassays. RESULTS: In the acupuncture group, 12 cases were cured, 16 cases markedly effective, and 6 cases improved, the total effective rate being as high as 97.14%. The decrease in the symptom scores, and especially the elevation of the decreased E2 level and the decrease of the increased FSH and LH levels, demonstrated that acupuncture therapy was superior to medication. CONCLUSION: Acupuncture for regulating the mental activities and reinforcing the kidney is an effective therapy for climacteric syndrome.

Acupuncture Therapy↗

[Effects of NaCl stress on Ca, Mg, Fe and Zn contents of different apple organs].

The study with two-year-old potted apple tree (Fuji variety with M. hupehensis Reld stock) showed that under NaCl stress, the average contents of Ca, Mg, Fe and Zn in different apple organs sampled at 4 periods had no significant changes, while the content ratios of test elements to Na decreased significantly, especially under high NaCl (3 per thousand) stress, which would result in the unbalance of mineral nutrients in the tree. The Ca content of different apple organs under and without NaCl stress was in order of trunk phloem > leaf and vegetative shoot > root > trunk xylem; Mg content was vegetative shoot and root > trunk xylem and phloem, and leaf; Fe content was root > leaf > trunk phloem and vegetative shoot > trunk xylem; Zn content was vegetative shoot > leaf > root and trunk phloem > trunk xylem. The element contents under NaCl stress showed different degrees of fluctuation, comparing with the control.

Calcium↗