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Chao Zhao

Publications and source records attributed to Chao Zhao.

At least 19 recordsLinked to original sources
PubMed2025

Genome-Wide Analysis of the AT-Hook Gene Family in Malus sieversii and Functional Characterization of MsAHL13.

AT-hook motif nuclear-localized (AHL) proteins are pivotal in plant growth, development, and stress responses. Nevertheless, there is limited research on AHL proteins in Malus sieversii. Our study identified 25 AHL genes from the M. sieversii genome, named MsAHL1-MsAHL25. The encoded protein sequences had lengths ranging from 195 to 554 amino acids, molecular weights from 19.17 to 58.53 kDa, and isoelectric points from 4.67 to 10.09. Chromosomal mapping revealed that these 25 genes were unevenly distributed across 10 chromosomes. Collinearity analysis of AHL genes in M. sieversii implied that gene loss might have occurred during its evolution. The phylogenetic tree classified the AHL proteins of M. sieversii into two subfamilies, showing a close relationship with multiple proteins of M. domestica. Promoter analysis indicated that the AHL genes in M. sieversii harbored numerous stress- and hormone-responsive elements, suggesting their potential role in various stress responses. qRT-PCR analysis of six representative MsAHLs under biotic and abiotic stresses demonstrated that the expression of MsAHL13, MsAHL15, and MsAHL17 was significantly upregulated under salt, drought, and cold stresses, while MsAHL01 expression was inhibited under low-temperature stress. All six MsAHLs were induced by the pathogen Valsa mali. Subcellular localization analysis of the specifically expressed protein MsAHL13 showed its nuclear location. Furthermore, luciferase and yeast two-hybrid assays confirmed the in vitro physical interaction between the MsAHL13 and MsMYB1 proteins. This research offers an important theoretical basis for further exploration of the functional mechanisms of this gene family in responding to environmental stresses.

Malus sieversii↗
PubMed2006

Stromal cell-derived factor 1alpha stimulates human endometrial carcinoma cell growth through the activation of both extracellular signal-regulated kinase 1/2 and Akt.

OBJECTIVE: The aim of study was to investigate the proliferative effects of stromal cell-derived factor-1alpha (SDF-1alpha) on endometrial carcinomas cell lines with different estrogen receptors (ER) and PTEN protein profiles. METHODS: MTT assays was used to detect the proliferation of HEC-1A and Ishikawa cells, and Western blotted analysis was used to detect activation of Akt and ERK1/2 in both cell lines after exposure to various concentrations of SDF-1alpha, MAPK-specific inhibitor PD98059 or PI3K-specific inhibitor LY294002. RESULTS: Low concentrations of SDF-1alpha ( 50 ng/ml) induced proliferation in both cell lines. ERK1/2 was significantly activated for more than 2 h by SDF-1alpha at 20 ng/ml in HEC-1A cells, but not in Ishikawa cells. In contrast, Akt was significantly activated for over 2 h in Ishikawa cells but remained unchanged in HEC-1A cells. High concentrations of SDF-1alpha activated Akt and ERK1/2 pathways in both cell lines in a dose-dependent manner, which was primarily inhibited by LY294002 for pAkt and by PD98059 for pERK 1/2. CONCLUSIONS: SDF-1alpha could stimulate the cell proliferation of endometrial carcinoma with different expression status of ER and PTEN in vitro, likely through the activation of both Akt and ERK1/2 signaling pathways.

Cell Line, Tumor↗
PubMed2006

Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS.

To assess the effects of sex on CNS remyelination, demyelinating lesions were induced by injection of ethidium bromide into the caudal cerebellar peduncle of Sprague-Dawley rats divided into the following 8 groups: young adult male, young adult female, old adult male and old adult female and each of these in which the gonads had been removed 4 weeks prior to lesion induction. Remyelination was assessed, blinded to grouping, by a ranking analysis using standard morphological criteria. In young adult animals, where remyelination proceeds rapidly, there was no difference in the remyelination at four weeks after lesion induction in male or females regardless of whether they were intact or castrated/ovariectomised. However, in old adult rats, where remyelination proceeds slowly, the extent of oligodendrocyte remyelination was significantly less in males compared to females at 8 weeks after lesion induction. Removal of gonads did not affect remyelination in old rats of either gender. These results indicate a sex-associated divergence in remyelination efficiency that occurs with ageing that is unaffected by the removal of gonadal sources of sex steroid hormones.

Aging↗
PubMed2006

Growth and activation of PI-3K/PKB and Akt by stromal cell-derived factor 1alpha in endometrial carcinoma cells with expression of suppressor endoprotein PTEN.

BACKGROUND: Mutation or deletion in the phosphatase and tensin homologue deleted on chromosome ten (PTEN) gene has been identified as an important cause of endometrial carcinoma; stromal cell derived factor-1alpha (SDF-1alpha) exerts growth-promoting effects on endometrial cancer cells through activation of the PI-3 kinase/Akt pathway and downstream effectors such as extracellular-responsive kinase (ERK). In this study, a plasmid containing the PTEN gene was transfected into Ishikawa cells to investigate the difference in growth and signal transduction between Ishikawa-PTEN and Ishikawa cells after SDF-1alpha stimulation, and to study mechanisms of the involvement of PTEN protein in endometrial carcinoma development. METHODS: Ishikawa cells were transfected with a plasmid (pLXSN-PTEN) containing the PTEN gene and a plasmid (pLXSN-EGFP) with enhanced green fluorescent protein (EGFP). Cells were then screened to obtain Ishikawa-PTEN cells and Ishikawa-neo cells that can both stably express PTEN protein and EGFP. Expression of PTEN protein, phosphorylation levels of AKT and ERK (pAKT and pERK) and growth differences in Ishikawa-PTEN, Ishikawa-neo and Ishikawa cells before and after SDF-1alpha stimulation were then determined by Western blots and MTT assays. RESULTS: Western blot analysis showed that Ishikawa cells produced PTEN after transfection with the PTEN gene. At 15 minutes after SDF-1alpha stimulation, the pAKT level of Ishikawa-PTEN cells was lower than that of Ishikawa-neo cells and Ishikawa cells. There was no significant difference in pERK levels among the three cell lines. The positive effect of SDF-1alpha on Ishikawa-PTEN cells growth was markedly less than the effect on Ishikawa-neo and Ishikawa cells. However, in the absence of SDF-1alpha stimulation (baseline), the pAKT level in Ishikawa-PTEN cells was less than that in Ishikawa cells. There was a significant difference in growth between the Ishikawa-PTEN cells and the Ishikawa-neo cells. CONCLUSIONS: PTEN gene transfection can regulate the level of pAKT but not pERK in Ishikawa-PTEN cells. PTEN protein may suppress the growth-promoting effect of SDF-1alpha on endometrial carcinoma by inhibiting the PI-3K/AKT signal transduction pathway.

Cell Line, Tumor↗
PubMed2006

Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation.

Demyelination in the adult CNS can be followed by extensive repair. However, in multiple sclerosis, the differentiation of oligodendrocyte lineage cells present in demyelinated lesions is often inhibited by unknown factors. In this study, we test whether myelin debris, a feature of demyelinated lesions and an in vitro inhibitor of oligodendrocyte precursor differentiation, affects remyelination efficiency. Focal demyelinating lesions were created in the adult rat brainstem, and the naturally generated myelin debris was augmented by the addition of purified myelin. After quantification of myelin basic protein mRNA expression from lesion material obtained by laser capture microdissection and supported by histological data, we found a significant impairment of remyelination, attributable to an arrest of the differentiation and not the recruitment of oligodendrocyte precursor cells. These data identify myelin as an inhibitor of remyelination as well as its well documented inhibition of axon regeneration.

Animals↗
PubMed2006

Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells.

Inflammation associated with CNS demyelination provides an important stimulus for the activation of endogenous oligodendrocyte precursor cells (OPCs) and subsequent remyelination. This view is largely based on "loss-of-function" studies, whereby remyelination is impaired following depletion of inflammatory cells or mediators. However, "gain-of-function" approaches, asking whether inflammation directly enhances remyelination, have received less attention. We have addressed this issue using a model in which OPCs transplanted into the adult rat retina myelinate retinal ganglion cell axons around the point of injection. Inflammation (characterized by increased expression of the macrophage marker ED1 and the astrocyte marker GFAP, and the up-regulation of multiple cytokines) was induced in the retina by the administration of the TLR-2 ligand zymosan. Myelination, revealed by MBP+ myelin sheaths, was substantially increased when OPCs were injected into the inflamed retina compared to that achieved following transplantation into the normal, noninflamed retina. Our results have important implications for the development of immunomodulatory treatments for acute demyelinating disease and for the therapeutic creation of proremyelination environments in chronic demyelinating disease.

Animals↗
PubMed2006

Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system.

High dose corticosteroid (CS) administration is a common mode of therapy in treatment of acute relapses in multiple sclerosis (MS) but the effects of CS on remyelination and the cellular mechanisms mediating this repair process are controversial. We have examined CS effects on repair of toxin-induced demyelinating lesions in the adult rat spinal cord. Corticosteroids reduced the extent of oligodendrocyte remyelination at 1 month post lesion (whereas Schwann-cell mediated repair was unaffected). However, CS did not cause permanent impairment of remyelination as lesions were fully remyelinated at 2 months after cessation of treatment. The delay in oligodendrocyte mediated repair could be attributed to inhibition of differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes, with no effect of CS treatment observed on OPC colonisation of the lesions. No differences were observed in animals treated with methylprednisolone succinate alone or with a subsequent prednisone taper indicating that CS effects occur at an early stage of repair. The potential consequences of delayed remyelination in inflammatory lesions are discussed.

Adrenal Cortex Hormones↗
PubMed2005

Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination.

CNS remyelination occurs more rapidly in young adult rats than in old rats. Since the inflammatory response initiated by demyelination is an important trigger for remyelination, we address whether ageing changes in remyelination are associated with changes in the inflammatory response. Using a toxin model of demyelination, where the inflammatory response largely comprises macrophages, we show that there is a delay in both recruitment and activation of OX-42+ and macrophage scavenger receptor B+ macrophages following demyelination in older rats (10-13 months) compared to young rats (8-10 weeks). This difference is associated with a slower onset of increased expression of several chemokine mRNAs. However, many inflammatory cytokines have similar mRNA expression patterns, with the exception of IL-1beta, IL-6 and TNF-alpha, which have prolonged expression in the older animals. Differences in IL-1beta mRNA expression, a cytokine specifically implicated in CNS remyelination, are not reflected in differences in protein expression detected by immunocytochemistry. These data relate the age-associated delay in remyelination efficiency to changes in the macrophage and inflammatory mediator response to demyelination.

Aging↗
PubMed2005

[Regulation of orphan receptor ERR alpha by estrogen and progesterone in endometrial carcinoma cell line].

OBJECTIVE: To explore the relationship between expression of ERR alpha mRNA and estrogen and progesterone and to elucidate the function of ERR alpha in endometrial carcinoma. METHODS: The expression of ERR alpha mRNA was examined by reverse transcription polymerase chain reaction. Endometrial carcinoma cell line Ishikawa was dealt with different concentrations of 17beta-estradiol (10(-10) mol/L, 10(-8) mol/L and 10(-6) mol/L) for 15 min, 30 min and 24 h and 17beta-estradiol and ER inhibitor-ICI182780 were given concomitantly to observe the change of ERR alpha mRNA. Different concentrations of progesterone (10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L and 10(-5) mol/L) were also given to Ishikawa cell line for 24 h to observe the change of ERR alpha mRNA. RESULTS: The expression level of ERR alpha mRNA was slightly higher than that of the control group after being stimulated for 15 min, 30 min and 24 h by 10(-10) mol/L 17beta-estradiol. However the expression level of ERR alpha mRNA was significantly lower than that of the control group after being stimulated for 15 min, 30 min and 24 h by 10(-8) mol/L and 10(-6) mol/L of 17beta-estradiol. When 10(-6) mol/L of ICI182780 and 10(-8) mol/L of 17beta-estradiol were given simultaneously to Ishikawa cell line, this down-regulation was blocked. After being stimulated for 24 h by 10(-7) mol/L, 10(-6) mol/L and 10(-5) mol/L of progesterone, the expression levels of ERR alpha mRNA were significantly higher than that of the control group, but no change was found in 10(-8) mol/L of progesterone. CONCLUSION: 17Beta-estradiol can down-regulate the expression of ERR alpha mRNA and this regulation is mediated by estrogen receptor. Progesterone can up-regulate the expression of ERR alpha mRNA.

Cell Line, Tumor↗
PubMed2005

Mechanisms of CNS remyelination--the key to therapeutic advances.

There are two components to the treatment of multiple sclerosis (MS); the first is to prevent damage occurring, and the second is to repair the residual damage. While considerable progress has been made in the recent years with the former through the development of anti-inflammatory and immunomodulatory therapies, there are currently no effective repair therapies routinely used in MS patients. This represents a significant gap in the MS clinician's therapeutic armoury. In this article we argue that a clear understanding of the repair mechanisms following CNS demyelination is fundamental to filling this gap. We discuss (1) the cellular events involved in remyelination, (2) changes in transcription factor expression within oligodendrocyte precursor cells associated with their activation in response to demyelination, (3) the role of platelet derived growth factor in the OPC recruitment phase of remyelination, and (4) the significance of the inflammatory response associated with demyelination in creating a signalling environment that favours remyelination.

Animals↗
PubMed2005

Synthesis, crystal structure and nuclease activity of a Schiff base copper(II) complex.

A new Schiff base copper(II) complex, Cu(o-VANAHE)(2) (o-VANAHE = 2-(o-vanillinamino)-1-hydroxyethane), has been synthesized and characterized. Single crystal X-ray diffraction results suggest that this complex structure belongs to triclinic crystal system, space group P1 with the following crystallographic parameters: a = 8.819(4) angstroms, b = 10.794(5) angstroms, c = 11.350(5) angstroms, alpha = 70.262(6) degrees, beta = 70.816(6) degrees, gamma = 78.360(6) degrees, V = 955.4(7) angstroms3, Z = 2, D(c) = 1.571 Mg x m(-3), and the final R1 = 0.0393, wR2 = 0.0994 for the observed reflections 2620(I > 2sigma(I)). The molecular geometry is almost coplanar. Viscosity, fluorescence spectroscopy and cyclic voltammetry have been conducted to assess their interaction between this complex and DNA. Results showed that the copper(II) complex can increase DNA's relative viscosity and quench the fluorescence intensity of EB bound to DNA. The adding of DNA to the solution of Cu(o-VANAHE)2 causes a slight decrease in the voltammetric current, as well as a slight shift in the E(1/2) to less negative potential. The interaction between the complex and DNA has also been investigated by submarine gel electrophoresis, interestingly, we found that the copper(II) complex can cleave circular plasmid pBR322 DNA to nicked and linear forms.

Copper↗
PubMed2005

Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination.

Minocycline, a tetracycline derivative, disrupts inflammatory processes within the CNS and reduces demyelination in experimental autoimmune encephalomyelitis. Several recent studies indicate that components of the inflammatory response to demyelination may be beneficial for the regenerative process of remyelination. In this study we examined the effects of minocycline on remyelination independent of its effects in limiting immune-mediated white matter damage using a toxin model of demyelination. Demyelinating lesions were induced by injection of ethidium bromide into caudal cerebellar peduncles of adult rats. Minocycline or PBS was administered by twice daily injections from day 1 prior to lesion-induction to post lesion day 3. Remyelination was assessed, blinded to grouping, using standard morphological criteria. The microglia activation within the lesion was assessed by examining the expression of OX-42 and major histocompatibility class II immunoreactivity. The oligodendrocyte progenitor cell (OPC) response was quantified by in situ hybridization using probes for OPC-expressed mRNAs, platelet-derived growth factor receptor-alpha and Olig-1. Minocycline treatment strongly inhibited microglia/macrophage activation at day 1 and day 3 post-lesion induction, and suppressed the OPC response to demyelination. We also found a significant decrease in the extent of oligodendrocyte but not Schwann cell remyelination in the minocycline-treated animals as compared with controls at 3 weeks post-lesion induction. These results indicate that microglia/macrophage activation is an important process for remyelination and further support the concept that suppression of inflammatory response may impair remyelination.

Animals↗
PubMed2005

Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression.

Although macrophages are mediators of CNS demyelination, they are also implicated in remyelination. To examine the role of macrophages in CNS remyelination, adult rats were depleted of monocytes using clodronate liposomes and demyelination induced in the spinal cord white matter using lysolecithin. In situ hybridization for scavenger receptor-B and myelin basic protein (MBP) revealed a transiently impaired macrophage response associated with delayed remyelination in liposome-treated animals. Macrophage reduction corresponded with delayed recruitment of PDGFRalpha+ oligodendrocyte progenitor cells (OPCs), which preceded changes in myelin phagocytosis, indicating a macrophage effect on OPCs independent of myelin debris clearance. Macrophage-depletion induced changes in the mRNA expression of insulin-like growth factor-1 and transforming growth factor beta1, but not platelet-derived growth factor-A and fibroblast growth factor-2. These data suggest that the macrophage response to toxin-induced demyelination influences the growth factor environment, thereby affecting the behavior of OPCs and hence the efficiency of remyelination.

Animals↗
PubMed2005

Stem cells, progenitors and myelin repair.

Remyelination, the process by which new myelin sheaths are restored to demyelinated axons, represents one of the most compelling examples of adult multipotent progenitor cells contributing to regeneration of the injured central nervous system (CNS). This process can occur with remarkable efficiency in both clinical disease, such as multiple sclerosis, and in experimental models, revealing an impressive ability of the adult CNS to repair itself. However, the inconsistency of remyelination in multiple sclerosis, and the loss of axonal integrity that results from its failure, makes enhancement of remyelination an important therapeutic objective. Identifying potential targets will depend on a detailed understanding of the cellular and molecular mechanisms of remyelination. In this article we address two important issues. First, we consider the nature of the cell or cells that respond to demyelination and generate new oligodendrocytes, identifying current areas of uncertainty and addressing the role of adult CNS stem and progenitor cells. Second, we discuss the concept of adult progenitor activation following demyelination, focusing on the increased expression of (1) olig transcription factors, (2) bone morphogenetic proteins and (3) fyn, a member of the src-family of tyrosine kinases.

Bone Morphogenetic Proteins↗
PubMed2005

[Expression of estrogen receptor-related receptor isoforms in endometrial carcinoma tissues and its clinical significance].

OBJECTIVE: To investigate the role of estrogen receptor-related receptor (ERR), a subfamily of orphan receptors, in the tumorigenesis of endometrial carcinoma and to evaluate the clinical significance. METHODS: A total of 46 cases of endometrial carcinoma tissues and 24 cases of normal endometrium tissues were collected. Semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to measure the expressions of ERR. All samples were classified into two groups according to ERalpha status. RESULTS: It was positively correlated between the ERR (alpha, beta, gamma) mRNA and protein expression (r = 0.462, P = 0.009; r = 0.689, P = 0.016 and r = 0.673, P = 0.001). The expression rate and level of ERRalpha mRNA in ERalpha-positive endometrial carcinoma (42%, 0.24 +/- 0.18) were lower than in normal endometrium (78%, 0.42 +/- 0.23; P = 0.019, P = 0.021). No significant difference was observed in the expression of ERRbeta mRNA between endometrial carcinoma (23%, 0.21 +/- 0.16) and normal endometrium (22%, 0.27 +/- 0.15; P > 0.05). In ERalpha-positive endometrial carcinoma, the expression level of ERRgamma mRNA (0.93 +/- 0.24) was higher than normal endometrium (0.72 +/- 0.21; P = 0.023). The numbers of patients of Federal International Gynecological Oncology (FIGO) stage II-IV and of deep myometrial invasion in ERRalpha mRNA positive endometrial carcinoma group were more than those in ERRalpha mRNA negative group (P = 0.017 and P = 0.033). ERRgamma mRNA positive patients had a lower occurrence of lymph metastases than negative patients (P = 0.021). CONCLUSIONS: ERR may be closely related with the tumorigenesis of endometrial carcinoma, similar to ER. ERRalpha may serve as a biomarker of poor prognosis and ERRgamma as a favorable biomarker in endometrial carcinoma.

Adult↗
PubMed2004

bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.

Olig1 and Olig2 are closely related basic helix-loop-helix (bHLH) transcription factors that are expressed in myelinating oligodendrocytes and their progenitor cells in the developing central nervous system (CNS). Olig2 is necessary for the specification of oligodendrocytes, but the biological functions of Olig1 during oligodendrocyte lineage development are poorly understood. We show here that Olig1 function in mice is required not to develop the brain but to repair it. Specifically, we demonstrate a genetic requirement for Olig1 in repairing the types of lesions that occur in patients with multiple sclerosis.

Animals↗
PubMed2004

Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS.

Within the adult CNS, a quiescent population of oligodendrocyte progenitor cells (OPCs) become activated in response to demyelination and give rise to remyelinating oligodendrocytes. During development, OPC differentiation is controlled by several transcription factors including Olig1 and Olig2, and Nkx2.2. We hypothesized that these genes may serve similar functions in activated adult OPCs allowing them to become remyelinating oligodendrocytes and tested this hypothesis by examining their expression during the remyelination of a toxin-induced rodent model of demyelination. During the acute phase of demyelination, OPCs within the lesion increased their expression of Nkx2.2 and Olig2, two transcription factors that in combination are critical for oligodendrocyte differentiation during developmental myelination. This activation was not associated with increases in Sonic hedgehog (Shh) expression, which does not appear essential for CNS remyelination. Consistent with a role in the activation and differentiation of OPCs, these increases were delayed in old adult animals where the rate of remyelination is slowed. Our data suggest the hypothesis that increased expression of Nkx2.2 and Olig2 plays a critically important role in the differentiation of adult OPCs into remyelinating oligodendrocytes and that these genes may present novel targets for therapeutic manipulation in cases where remyelination is impaired.

Animals↗