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Biomedical subjects

H J Cao

Publications and source records attributed to H J Cao.

At least 19 recordsLinked to original sources
PubMed2004

Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells.

Resveratrol, a naturally occurring stilbene, induced apoptosis in human breast cancer MCF-7 cells. The mechanism of this effect was dependent on mitogen-activated protein kinase (MAPK, ERK1/2) activation and was associated with serine phosphorylation and acetylation of p53. Treatment of MCF-7 cells with resveratrol in the presence of 17beta-oestradiol (E(2)) further enhanced MAPK activation, but E(2) blocked resveratrol-induced apoptosis, as measured by nucleosome ELISA and DNA fragmentation assays. E(2) inhibited resveratrol-stimulated phosphorylation of serines 15, 20 and 392 of p53 and acetylation of p53 in a concentration- and time-dependent manner. These effects of E(2) on resveratrol action were blocked by ICI 182,780 (ICI), an inhibitor of the nuclear oestrogen receptor-alpha (ER). ICI 182,780 did not block the actions of resveratrol, alone. Electrophoretic mobility studies of p53 binding to DNA and of p21 expression indicated that E(2) inhibited resveratrol-induced, p53-directed transcriptional activity. These results suggest that E(2) inhibits p53-dependent apoptosis in MCF-7 cells by interfering with post-translational modifications of p53 which are essential for p53-dependent DNA binding and consequent stimulation of apoptotic pathways. These studies provide insight into the complex pathways by which apoptosis is induced by resveratrol in E(2)-depleted and -repleted environments.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Prostaglandin endoperoxide H synthase expression in human thyroid epithelial cells.

KAT-50, an established human thyrocyte cell line, expresses constitutively high levels of prostaglandin endoperoxide H synthase-2 (PGHS-2), the inflammatory cyclooxygenase. Here, we examine primary human thyrocytes. We find that they, too, express PGHS-2 mRNA and protein under control culture conditions. A substantial fraction of the basal prostaglandin E(2) (PGE(2)) produced by these cells can be inhibited by SC-58125 (5 microM), a PGHS-2-selective inhibitor. Interleukin (IL)-1beta (10 ng/ml) induces PGHS-2 expression and PGE(2) production in primary thyrocytes. The induction of PGHS-2 and PGE(2) synthesis by IL-1beta could be blocked by glucocorticoid treatment. Unlike KAT-50, most of the culture strains also express PGHS-1 protein. Our observations suggest that both cyclooxygenase isoforms may have functional roles in primary human thyroid epithelial cells, and PGHS-2 might predominate under basal and cytokine-activated culture conditions.

Cells, Cultured↗
PubMed2001

[Congenital absence of upper anterior teeth a dentofacial morphologic analysis].

OBJECTIVE: This study was designed to examine the dentofacial morphology of the children in Shanghai with congenital absence of upper anterior teeth. METHODS: Cephalometric analysis for 37 children with congenital absence of upper anterior teeth was conducted and was compared with that of the normal ones. RESULTS: (1) There was no significant difference in all measurements between gender. (2) Craniofacial defection included a small SNA a small ANB a small AoBo a small angle of convexity,and a large AB plane angle. Vertical facial dimensions which was shown by Y axis and mandibular plane angle significantly decreased. Examination for soft tissue also revealed a small convexity of soft tissue and a large CmSnUL. (3) A compensative proclination of the upper central incisors as well as the upper lip was also found. CONCLUSION: Patients with congenital absence of upper anterior teeth might have a small maxilla a relatively normal mandibular dimension an anticlock rotation of the mandible plane, and a compensative proclination of the upper central incisors and the upper lip.

English Abstract↗
PubMed2001

[A clinical study on two forces orthodontic technique].

OBJECTIVE: Two Forces Technique was introduced in order to extend its use in daily clinical practice. The advantages of this technique were also mentioned. METHODS: Various kinds of malocclusion were treated by using Broussard brackets and auxiliary springs according to Two Forces Technique procedure. RESULTS: Satisfied treatment results were achieved based on the comparison of cephalometrics before and after orthodontic treatment. CONCLUSION: Auxiliary springs and light force were used in this technique, which moved teeth in three dimension precisely. It can be used in correction of various kinds of malocclusion and is easy to manipulate in clinics.

English Abstract↗
PubMed2000

Peroxisome proliferator activator receptor-gamma agonists and 15-deoxy-Delta(12,14)(12,14)-PGJ(2) induce apoptosis in normal and malignant B-lineage cells.

The research described herein evaluates the expression and functional significance of peroxisome proliferator activator receptor-gamma (PPAR-gamma) on B-lineage cells. Normal mouse B cells and a variety of B lymphoma cells reflective of stages of B cell differentiation (e.g., 70Z/3, CH31, WEHI-231, CH12, and J558) express PPAR-gamma mRNA and, by Western blot analysis, the 67-kDa PPAR-gamma protein. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), a PPAR-gamma agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [(3)H]thymidine and 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assays. Only PPAR-gamma agonists (thiazolidinediones), and not PPAR-alpha agonists, mimicked the effect of 15d-PGJ(2) on B-lineage cells, indicating that the mechanism by which 15d-PGJ(2) negatively affects B-lineage cells involves in part PPAR-gamma. The mechanism by which PPAR-gamma agonists induce cytotoxicity is via apoptosis, as shown by annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay. Interestingly, addition of PGF(2alpha), which was not known to affect lymphocytes, dramatically attenuated the deleterious effects of PPAR-gamma agonists on B lymphomas. Surprisingly, 15d-PGJ(2) induced a massive increase in nuclear mitogen-activated protein kinase activation, and pretreatment with PGF(2alpha) blunted the mitogen-activated protein kinase activation. This is the first study evaluating PPAR-gamma expression and its significance on B lymphocytes. PPAR-gamma agonists may serve as a counterbalance to the stimulating effects of other PGs, namely PGE(2), which promotes B cell differentiation. Finally, the use of PGs, such as 15d-PGJ(2), and synthetic PPAR-gamma agonists to induce apoptosis in B-lineage cells may lead to the development of novel therapies for fatal B lymphomas.

Animals↗
PubMed2000

[A study on dental and cranioficial structure of normal shanghai adults occlusion-I the craniofacial structure analysis with posterioanterior cephalometric roentgenography]

OBJECTIVE: To evaluate the characteristics of normal transverse craniofacial structure in Shanghai area and to establish the database of normal Shanghai adults occlusion for posterioanterior cephalometric roentgenography.METHODS:Posterioanterior-cephalometric of the 92 adults subjects with normalocclusion were measured and analysed by Jiffy orthodontic evaluation 5.0 software package.RESULTS:The database of normal Shanghai adults occlusion for posterioanterior cephalometric roentgenography was established. Transverse measurements were intercorrelated, no statistically significant gender differences were demonstrated in craniofacial width, while the molar overjet of male was larger than that of female.CONCLUSION:The normal transverse cranioficial structure in Shanghai area has its own characteristics. The established database would provide a foundation for the diagnosis and treatment of malocclusion.

Journal Article↗
PubMed1999

Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium. Evidence for constitutive expression in vivo and in cultured KAT-50 cells.

Prostaglandin-endoperoxide H synthase (PGHS) (EC 1.14.99.1) expression was examined in human thyroid tissue and in KAT-50, a well differentiated human thyroid epithelial cell line. PGHS-1 is found constitutively expressed in most healthy tissues, whereas PGHS-2 is highly inducible and currently thought to be expressed, with few exceptions, only in diseased tissues. Surprisingly, PGHS-2 mRNA and protein were easily detected in normal thyroid tissue. KAT-50 cells express high levels of constitutive PGHS-2 mRNA and protein under basal culture conditions. Compounds usually associated with PGHS-2 induction, including interleukin-1beta (IL-1beta), phorbol 12-myristate 13-acetate, and serum transiently down-regulated PGHS-2 expression. Human PGHS-2 promoter constructs (-1840/+123 and -831/+123) fused to a luciferase reporter and transfected into untreated KAT-50 cells exhibited substantial activity. NS-398, a highly selective inhibitor of PGHS-2 could inhibit substantial basal prostaglandin E2 production. Exogenous IL-1 receptor antagonist or IL-1alpha neutralizing antibodies could attenuate constitutive PGHS-2 expression in KAT-50 cells, suggesting that endogenous IL-1alpha synthesis was driving PGHS-2 expression. Our findings suggest that normal thyroid epithelium expresses high constitutive levels of PGHS-2 in situ and in vitro and this enzyme is active in the generation of prostaglandin E2. Thus, unprovoked PGHS-2 expression might be considerably more widespread in healthy tissues than is currently believed.

Cell Line↗
PubMed1999

The effect of cigarette smoke constituents on the expression of HLA-DR in orbital fibroblasts derived from patients with Graves ophthalmopathy.

PURPOSE: Numerous studies have established a strong association between smoking and Graves disease, but the underlying mechanism of Graves ophthalmopathy has not been elucidated. Recent studies of Graves ophthalmopathy have focused on the orbital fibroblast as an integral component in the pathogenesis of this disorder. This investigation focuses on the effect of cigarette smoke constituents, nicotine and tar, to alter the expression of human leukocyte antigen (HLA-DR) in cultured orbital fibroblasts from patients with Graves disease. METHODS: HLA-DR expression was quantified by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate--polyacrylamide gel electrophoresis with immunoblotting and also by direct immunofluorescence. RESULTS: Cultured orbital fibroblasts, obtained from patients undergoing orbital decompression for severe Graves ophthalmopathy, failed to express HLA-DR as analyzed by both immunoblotting and direct immunofluorescence when treated with nicotine alone (25-300 ng/ml). The expression of HLA-DR increased three-fold when nicotine (25 ng/ml) in combination with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). Cultured orbital fibroblasts treated with tar alone (60-600 ng/ml) failed to exhibit HLA-DR expression as assessed by direct immunofluorescence and immunoblotting. A greater than two-fold increase in HLA-DR expression occurred when tar (600 ng/ml) combined with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). CONCLUSION: The results suggest a possible molecular mechanism for the more severe ophthalmopathy observed in Graves patients who smoke cigarettes. These findings could prove useful for possible medical interventions to decrease or even inhibit the interaction between cigarette constituents, cytokines, and orbital fibroblasts.

Cells, Cultured↗
PubMed1999

Leukoregulin upregulation of prostaglandin endoperoxide H synthase-2 expression in human orbital fibroblasts.

Human orbital fibroblasts from patients with severe thyroid-associated ophthalmopathy are particularly susceptible to the actions of a variety of proinflammatory molecules. In this study, we demonstrate that the inductions of prostaglandin endoperoxide H synthase-2 (PGHS-2), interleukin (IL)-1alpha, and IL-1beta by leukoregulin, a product of activated T lymphocytes, are far more robust in orbital fibroblasts than those observed in dermal fibroblasts. These actions of leukoregulin are mediated through an intermediate induction of IL-1alpha. In contrast, leukoregulin also induces IL-1-receptor antagonist (IL-1ra) expression in orbital fibroblasts, but this induction is considerably greater in dermal fibroblasts (2.3- vs. 8.5-fold). Interrupting the effects of IL-1alpha, either with a neutralizing antibody or with exogenous IL-1ra, can block the induction of PGHS-2 by leukoregulin. Leukoregulin increases PGHS-2 gene transcription in orbital fibroblasts but exerts the major effect on cyclooxygenase expression by enhancing the stability of mature PGHS-2 mRNA. The cytokine triggers nuclear translocation of nuclear factor-kappaB (NF-kappaB) p50/p50 homodimers and p50/p65 heterodimers, and an inhibitor of this transcriptional factor, pyrrolidinedithiocarbamate, can attenuate the PGHS-2 induction. Thus differential inducibility of the members of the IL-1 family of genes in orbital fibroblasts would appear to underlie, at least in part, the differences in PGHS-2 induction observed in orbital and dermal fibroblasts. NF-kappaB plays an important role in mediating the effects of leukoregulin on PGHS-2 expression.

Anti-Inflammatory Agents↗
PubMed1998

Activation of human orbital fibroblasts through CD40 engagement results in a dramatic induction of hyaluronan synthesis and prostaglandin endoperoxide H synthase-2 expression. Insights into potential pathogenic mechanisms of thyroid-associated ophthalmopathy.

Human orbital fibroblasts play a putative role in the pathogenesis of thyroid-associated ophthalmopathy (TAO). We hypothesize that the hyaluronan accumulation and inflammation in TAO derive from enhanced biosynthetic activities of orbital fibroblasts. CD40, a member of the tumor necrosis factor-alpha receptor superfamily, is a critical signaling molecule expressed by B lymphocytes. Engagement of CD40 with CD154 or CD40 ligand results in the activation of target genes. Orbital fibroblasts also display CD40. Here we report that CD40 engagement leads to substantial increases in hyaluronan synthesis in orbital fibroblasts. The increase is approximately 5-fold above control values, is comparable to the induction elicited by IL-1beta and could be attenuated with dexamethasone but not by SC 58125, a prostaglandin endoperoxide H synthase-2 (PGHS-2)-selective inhibitor. PGHS-2 is also induced by CD40 engagement in a time-dependent manner, and this is mediated through increases in levels of steady-state mRNA. The induction of PGHS-2 leads to a dramatically enhanced prostaglandin E2 production that can be blocked by SC 58125 and dexamethasone. CD40 ligand up-regulates the synthesis of IL-1alpha, and blocking this cytokine with exogenous IL-1 receptor antagonist (IL-1ra) or with IL-1alpha neutralizing antibodies partially attenuates the induction of PGHS-2. In contrast, CD40 ligand up-regulation of hyaluronan synthesis is unaffected by IL-1ra. CD40 cross-linking enhances mitogen-activated protein kinase activation, and interrupting this pathway attenuates the PGHS-2 induction. Thus the CD40/CD40 ligand bridge represents a potentially important activational pathway for orbital fibroblasts that may underlie the cross-talk between these cells and leukocytes. These findings may be relevant to the pathogenesis of TAO and provide insights into previously unrecognized, potential therapeutic targets.

CD40 Antigens↗
PubMed1998

CD40 engagement up-regulates cyclooxygenase-2 expression and prostaglandin E2 production in human lung fibroblasts.

A newly emerging view of fibroblasts is that they are vital for initiating inflammation and respond to and direct the activities of leukocytes. Human fibroblasts can express CD40, an activation Ag the ligand of which is displayed by activated leukocytes. We demonstrate here that CD40 engagement on human lung fibroblasts dramatically increases proinflammatory PGE2 synthesis. This up-regulation is mediated through an induction of cyclooxygenase-2 (Cox-2) since Cox-2-selective inhibitors block the up-regulation. Western and Northern blot analyses demonstrated that Cox-2 protein and mRNA are dramatically increased in fibroblasts following CD40 engagement. We conclude that CD40 is a major pathway in human fibroblasts for the induction of Cox-2. There is intense interest in devising strategies for disruption of the CD40-CD40 ligand system to blunt inflammation. Such an intervention would be expected to attenuate the up-regulation of fibroblast Cox-2 and PGE2 production at the site of tissue injury.

CD40 Antigens↗
PubMed1998

Cytokine-mediated PGE2 expression in human colonic fibroblasts.

We investigated prostanoid biogenesis in human colonic fibroblasts (CCD-18Co and 5 primary fibroblast cultures) and epithelial cell lines (NCM460, T84, HT-29, and LS 174T) and the effect of PGE2 on fibroblast morphology. Cytokine-stimulated PGE2 production was measured. PGH synthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression were evaluated. Basal PGE2 levels were low in all cell types (0.15-6.47 ng/mg protein). Treatment for 24 h with interleukin-1beta (IL-1beta; 10 ng/ml) or tumor necrosis factor-alpha (50 ng/ml), respectively, elicited maximal 25- and 6-fold inductions of PGE2 synthesis in CCD-18Co cultures and similar results in primary fibroblast cultures; maximal inductions with IL-1beta in colonic epithelial cell lines were from zero to fivefold. Treatment of CCD-18Co fibroblasts with IL-1beta caused maximal 21- and 53-fold increases, respectively, in PGHS-2 protein and mRNA levels without altering PGHS-1 expression. PGE2 (0.1 micromol/l) elicited a dramatic shape change in selected fibroblasts. Colonic fibroblasts are potentially important as cytokine targets and a source of and target for colonic prostanoids in vivo.

Cell Line↗
PubMed1997

Human thyroid fibroblasts exhibit a distinctive phenotype in culture: characteristic ganglioside profile and functional CD40 expression.

Fibroblasts from different regions of the human body exhibit substantial phenotypic diversity, some of which relates to the capacity for cross-talk with cells of the immune system. We examine, for the first time, thyroid fibroblast biology in culture. Thyroid explants were placed in culture, and fibroblasts were outgrown and serially passaged. These fibroblasts take on a morphology in culture resembling cells from other anatomic regions. When treated with PGE2, they assume a stellate morphology similar to that of prostanoid-treated orbital fibroblasts. The ganglioside profile exhibited by these cells is distinct from that observed previously in orbital and dermal fibroblasts. They uniformly express Thy-1, a surface glycoprotein. Messenger RNA encoding CD40, a surface receptor found on bone marrow-derived cells, and CD40 protein were expressed constitutively at low levels. Interferon-gamma (500 U/ml) treatment for 48-72 h resulted in high levels of surface HLA-DR and CD40 display. When CD40 is engaged with CD40 ligand (CD40L), nuclear factor-kappaB binding activity is up-regulated as is interleukin (IL)-6 and IL-8 expression. IL-1beta treatment up-regulates the expression of IL-1alpha, IL-1beta, and PGE2. These observations suggest that thyroid fibroblasts possess the molecular machinery necessary for cross-talk with immunocompetent cells such as lymphocytes and mast cells through the CD40/CD40L complex, as well as through classic cytokine networks, and to participate potentially in the inflammatory response of the thyroid gland.

CD40 Antigens↗