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Biomedical subjects

Fan Zhang

Publications and source records attributed to Fan Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2004

Effect of Shenfu Injection (ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells and its mechanism during ischemia-reperfusion in rats.

OBJECTIVE: To investigate the effect of Shenfu Injection (SF, ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion in rats and its potential mechanisms. METHODS: Ischemia-reperfusion model was established in rats. Twenty-four rats were divided into 3 groups with 8 rats in each, eg, ischemia-reperfusion (I/R) group, SF-treated group, and control group. In both SF and I/R groups, the superior mesenteric artery was closed with forceps for 1 hour and then reperfused for 2 hours. Either SF (3 ml/kg, SF group) or normal saline (I/R and control groups) was injected intravenously and continuously for 5 ml/kg with a micropump before the superior mesenteric artery was closed. The superior mesenteric artery was not closed for animals in control group. The expression of casapse-3 and Fas, and the level of TNF-alpha and pathological changes of the ileal mucosal tissue were assayed. RESULTS: (1) The number of apoptosis cells increased obviously in I/R group and was significantly higher than that in SF and control groups (P<0.05). (2) The expression of caspase-3, Fas, and TNF-alpha was significantly higher in I/R group than SF and control groups (P<0.01); however, there was not significant difference in the expression of capase-3 between control group and SF group. There was a positive correlation between the expression of caspase-3, Fas, and TNF-alpha, and the number of apoptosis cells. (3) Under light microscope, intestinal mucosal impairment was found milder in SF group than I/R group (P<0.05). CONCLUSIONS: SF can depress the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion by restraining the expression of TNF-alpha, Fas, caspase-3, and accordingly alleviate the ischemia and reperfusion injury of intestinal mucosal epithelial cells.

Animals↗
PubMed2004

[A case-control study on the relationship between stroke and plasma homocysteine level and the mutation of MTHFR gene].

OBJECTIVE: To study the relationship of stroke and plasma homocysteine (Hcy) level and the mutation of methylenetetrahydrofolate reductase (MTHFR) gene. METHODS: Three hundred patients with stroke were included as the case group in this study while 300 subjects without stroke matched with the case group for sex and age were collected as the control group. Plasma Hcy level was measured using HPLC and MTHFR 667C-->T mutant was determined by polymerase chain reaction and restriction fragment analysis. The relationship of stroke and plasma Hcy level and the mutation of MTHFR gene was then analysed. RESULTS: The plasma Hcy level of the case group was significantly higher than that of the control group (16.92 +/- 3.43 micromol/L vs. 14.57 +/- 2.59 micromol/L, P <0.05). There was no significant difference in mutation rate of MTHFR C677T between stroke group and control group (P >0.05), as well as between ischemic stroke group and homorrhagic stroke group (P >0.05). The mutation of MTHFR C677T had no significant influence on the Hcy level (15.28 +/- 2.17 micromol/L vs. 15.11 +/- 3.81 micromol/L, P >0.05). CONCLUSION: Increased plasma Hcy level played an important role in the occurrence of stroke in Chinese people, and the mutation of MTHFR C677T was not associated with Hcy level or stroke which led to the speculation that plasma Hcy level was important in the prevention of cardio-cerebro-vascular diseases among Chinese people.

Case-Control Studies↗
PubMed2003

Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis.

The molecular pathways involved in the differentiation of hematopoietic progenitors are unknown. Here we report that chemokine-mediated interactions of megakaryocyte progenitors with sinusoidal bone marrow endothelial cells (BMECs) promote thrombopoietin (TPO)-independent platelet production. Megakaryocyte-active cytokines, including interleukin-6 (IL-6) and IL-11, did not induce platelet production in thrombocytopenic, TPO-deficient (Thpo(-/-)) or TPO receptor-deficient (Mpl(-/-)) mice. In contrast, megakaryocyte-active chemokines, including stromal-derived factor-1 (SDF-1) and fibroblast growth factor-4 (FGF-4), restored thrombopoiesis in Thpo(-/-) and Mpl(-/-) mice. FGF-4 and SDF-1 enhanced vascular cell adhesion molecule-1 (VCAM-1)- and very late antigen-4 (VLA-4)-mediated localization of CXCR4(+) megakaryocyte progenitors to the vascular niche, promoting survival, maturation and platelet release. Disruption of the vascular niche or interference with megakaryocyte motility inhibited thrombopoiesis under physiological conditions and after myelosuppression. SDF-1 and FGF-4 diminished thrombocytopenia after myelosuppression. These data suggest that TPO supports progenitor cell expansion, whereas chemokine-mediated interaction of progenitors with the bone marrow vascular niche allows the progenitors to relocate to a microenvironment that is permissive and instructive for megakaryocyte maturation and thrombopoiesis. Progenitor-active chemokines offer a new strategy to restore hematopoiesis in a clinical setting.

Animals↗
PubMed2003

Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen.

Although the accelerated atherosclerosis and premature aging of the cardiovascular system in patients with metabolic syndrome have been appreciated, the mechanisms of their development and potential therapeutic interventions remain unresolved. Our previous studies implicated advanced glycosylation end products in development of premature senescence preventable with a peroxynitrite scavenger, ebselen. Therefore, the effect of ebselen on endothelial senescence and vasculopathy in a model of metabolic syndrome--Zucker diabetic rats (ZDF)--was investigated. Ebselen decreased the abundance of 3-nitrotyrosine-modified proteins in ZDF rats. A 6-fold increase in the number of senescent endothelial cells in 22-week-old ZDF was prevented by ebselen. Development of vasculopathy, as collectively judged by the acetylcholine-induced vasorelaxation, NO production, angiogenic competence, and number of circulating microparticles, was almost completely prevented when ebselen was administered from 8 to 22 weeks and partially reversed when the treatment interval was 13 to 22 weeks. In conclusion, premature senescence of endothelial cells is progressively rampant in ZDF rats and is associated with the signs of severe vasculopathy. In addition, prevention of premature senescence of vascular endothelium through controlled decrease in nitrotyrosine formation was chronologically associated with the amelioration of vasculopathy, lending support to the idea of the pathogenetic role of premature senescence of endothelial cells in diabetic macrovasculopathy.

Acetylcholine↗
PubMed2003

On and off: proteasome and TGF-beta signaling.

Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF-beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is mediated by the ubiquitin-proteasome system. Inhibition of the proteasome activity causes accumulation of these components in the cells and modulates TGF-beta signaling in a time-dependent and gene-specific manner. The accelerated degradation of TGF-beta signaling components via the proteasome system has been found in a number of tumors, indicating that dysregulated proteasomal degradation is a novel pathway how tumor cells silence TGF-beta signaling.

Animals↗
PubMed2003

Adenovirus E4 gene promotes selective endothelial cell survival and angiogenesis via activation of the vascular endothelial-cadherin/Akt signaling pathway.

The early 4 region (E4) of the adenoviral vectors (AdE4(+)) prolongs human endothelial cell (EC) survival and alters the angiogenic response, although the mechanisms for the EC-specific, AdE4(+)-mediated effects remain unknown. We hypothesized that AdE4(+) modulates EC survival through activation of the vascular endothelial (VE)-cadherin/Akt pathway. Here, we showed that AdE4(+), but not AdE4(-) vectors, selectively stimulated phosphorylation of both Akt at Ser(473) and Src kinase in ECs. The phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin abrogated AdE4(+) induction of both phospho-Akt expression and prolonged EC survival. Regulation of phospho-Akt was found to be under the control of various factors, namely VE-cadherin activation, Src kinase, tyrosine kinase, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Downstream targets of Akt signaling resulted in glycogen synthase kinase-3alpha/beta phosphorylation, beta-catenin up-regulation, and caspase-3 suppression, all of which led to AdE4(+)-mediated EC survival. Furthermore, infection with AdE4(+) vectors increased the angiogenic potential of ECs by promoting EC migration and capillary tube formation in Matrigel plugs. This selective AdE4(+)-mediated enhanced motility of ECs was also blocked by PI3K inhibitors. Taken together, these results suggest that activation of the VE-cadherin/Akt pathway is critical for AdE4(+)-mediated survival of ECs and angiogenic potential.

Adenovirus E4 Proteins↗
PubMed2003

Alternative promoters regulate transcription of the gene that encodes stem cell surface protein AC133.

AC133 is a member of a novel family of cell surface proteins with 5 transmembrane domains. The function of AC133 is unknown. Although AC133 mRNA is detected in different tissues, its expression in the hematopoietic system is restricted to CD34+ stem cells. AC133 is also expressed on stem cells of other tissues, including endothelial progenitor cells. However, despite the potential importance of AC133 to the field of stem cell biology, nothing is known about the transcriptional regulation of AC133 expression. In this report we showed that the human AC133 gene has at least 9 distinctive 5'-untranslated region (UTR) exons, resulting in the formation of at least 7 alternatively spliced 5'-UTR isoforms of AC133 mRNA, which are expressed in a tissue-dependent manner. We found that transcription of these AC133 isoforms is controlled by 5 alternative promoters, and we demonstrated their activity on AC133-expressing cell lines using a luciferase reporter system. We also showed that in vitro methylation of 2 of these AC133 promoters completely suppresses their activity, suggesting that methylation plays a role in their regulation. Identification of tissue-specific AC133 promoters may provide a novel method to isolate tissue-specific stem and progenitor cells.

5' Untranslated Regions↗
PubMed2003

The bHLH genes GLABRA3 (GL3) and ENHANCER OF GLABRA3 (EGL3) specify epidermal cell fate in the Arabidopsis root.

The position-dependent specification of the hair and non-hair cell types in the Arabidopsis root epidermis provides a simple model for the study of cell fate determination in plants. Several putative transcriptional regulators are known to influence this cell fate decision. Indirect evidence from studies with the maize R gene has been used to suggest that a bHLH transcription factor also participates in this process. We show that two Arabidopsis genes encoding bHLH proteins, GLABRA3 (GL3) and ENHANCER OF GLABRA3 (EGL3), act in a partially redundant manner to specify root epidermal cell fates. Plants homozygous for mutations in both genes fail to specify the non-hair cell type, whereas plants overexpressing either gene produce ectopic non-hair cells. We also find that these genes are required for appropriate transcription of the non-hair specification gene GL2 and the hair cell specification gene CPC, showing that GL3 and EGL3 influence both epidermal cell fates. Furthermore, we show that these bHLH proteins require a functional WER MYB protein for their action, and they physically interact with WER and CPC in the yeast two-hybrid assay. These results suggest a model in which GL3 and EGL3 act together with WER in the N cell position to promote the non-hair cell fate, whereas they interact with the incomplete MYB protein CPC in the H position, which blocks the non-hair pathway and leads to the hair cell fate.

Arabidopsis↗
PubMed2003

CO modulates pulmonary vascular response to acute hypoxia: relation to endothelin.

Pulmonary intralobar arteries express heme oxygenase (HO)-1 and -2 and release carbon monoxide (CO) during incubation in Krebs buffer. Acute hypoxia elicits isometric tension development (0.77 +/- 0.06 mN/mm) in pulmonary vascular rings treated with 15 micromol/l chromium mesoporphyrin (CrMP), an inhibitor of HO-dependent CO synthesis, but has no effect in untreated vessels. Acute hypoxia also induces contraction of pulmonary vessels taken from rats injected with HO-2 antisense oligodeoxynucleotides (ODN), which decrease pulmonary HO-2 vascular expression and CO release. Hypoxia-induced contraction of vessels treated with CrMP is attenuated (P < 0.05) by endothelium removal, by CO (1-100 micromol/l) in the bathing buffer, and by endothelin-1 (ET-1) receptor blockade with L-754142 (10 micromol/l). CrMP increases ET-1 levels in pulmonary intralobar arteries, particularly during incubation in hypooxygenated media. CrMP also causes a leftward shift in the concentration-response curve to ET-1, which is offset by exogenous CO. In anesthetized rats, pretreatment with CrMP (40 micromol/kg iv) intensifies the elevation of pulmonary artery pressure elicited by breathing a hypoxic gas mixture. However, acute hypoxia does not elicit augmentation of pulmonary arterial pressure in rats pretreated concurrently with CrMP and the ET-1 receptor antagonist L-745142 (15 mg/kg iv). These data suggest that a product of HO activity, most likely CO, inhibits hypoxia-induced pulmonary vasoconstriction by reducing ET-1 vascular levels and sensitivity.

Acute Disease↗
PubMed2003

Ski-related novel protein N (SnoN), a negative controller of transforming growth factor-beta signaling, is a prognostic marker in estrogen receptor-positive breast carcinomas.

Transforming growth factor (TGF)-beta arrests the growth of breast epithelial cells, whereas breast cancer cells are highly resistant to its growth restrictive properties. To define causes for the defect in TGF-beta action, we present here the first in vivo analysis of Ski-related novel protein N (SnoN), a negative regulator of TGF-beta signaling, in human breast carcinomas. SnoN expression was analyzed by immunohistochemistry in a tissue microarray of 1122 breast carcinomas and 10 reduction mammoplasties. In the normal breast, SnoN was located predominantly in nuclei of large duct epithelial cells and the cytoplasm of terminal duct epithelial cells. Breast cancers displayed variances in both SnoN expression levels and subcellular localizations. High levels of cytoplasmic SnoN were more often observed in tumors of ductal histological type and associated with adverse prognostic features, such as lack of hormone receptors; high levels of p53, Ki-67, and cyclooxygenase-2; and amplifications of HER-2. High levels of nuclear SnoN were associated with lobular histology and favorable features, including presence of hormone receptors, low expression of p53 and Ki-67, and lack of HER-2 amplifications. Reduced expression of SnoN significantly correlated with longer distant disease-free survival in estrogen receptor-positive patients (P = 0.0027, relative risk = 3.27; 95% confidence interval = 1.44-7.41). The results suggest that the subcellular localization of SnoN may have clinical significance and that reduced expression of SnoN is associated with favorable outcome in estrogen receptor-positive breast cancer.

Adult↗
PubMed2003

A network of redundant bHLH proteins functions in all TTG1-dependent pathways of Arabidopsis.

GLABRA3 (GL3) encodes a bHLH protein that interacts with the WD repeat protein, TTG1. GL3 overexpression suppresses the trichome defect of the pleiotropic ttg1 mutations. However, single gl3 mutations only affect the trichome pathway with a modest trichome number reduction. A novel unlinked bHLH-encoding locus is described here, ENHANCER OF GLABRA3 (EGL3). When mutated, egl3 gives totally glabrous plants only in the gl3 mutant background. The double bHLH mutant, gl3 egl3, has a pleiotropic phenotype like ttg1 having defective anthocyanin production, seed coat mucilage production, and position-dependent root hair spacing. Furthermore, the triple bHLH mutant, gl3 egl3 tt8, phenocopies the ttg1 mutation. Yeast two-hybrid and plant overexpression studies show that EGL3, like GL3, interacts with TTG1, the myb proteins GL1, PAP1 and 2, CPC and TRY, and it will form heterodimers with GL3. These results suggest a combinatorial model for TTG1-dependent pathway regulation by this trio of partially functionally redundant bHLH proteins.

Arabidopsis↗
PubMed2003

Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells.

Reporter genes, including green fluorescent protein (GFP), have been used to monitor the expression of transgenes introduced into vascular cells by gene transfer vectors. Here, we demonstrate that GFP by itself can selectively induce expression of certain genes in endothelial cells. Elevation of the cytoplasmic concentration of GFP in endothelial cells, specifically, resulted in a robust upregulation of heat shock protein 70 (HSP70). GFP induced both mRNA and protein expression of HSP70 in a dose-dependent manner. GFP-mediated up-regulation of HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin E2 (PGE2) production. GFP-mediated up-regulation of HSP70 is independent of mitogen-activated protein kinase and phosphatidylinositol-3-kinase signaling cascades because inhibition of these pathways had no effect on HSP70 increases. Adenoviral delivery of GFP into murine vasculature significantly enhanced blood flow, suggesting that sufficient PGE2 is produced to induce vasodilation. Identification of the molecular partners that interact with GFP will increase our understanding of the vascular-specific factors that regulate stress angiogenesis and hemostasis.

Adenoviridae↗
PubMed2003

Correlation between HER-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide in patients with breast carcinoma.

BACKGROUND: The objective of this study was to determine whether HER-2 overexpression is associated with improved response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) in patients with breast carcinoma. METHODS: Ninety-seven patients with Stage I-III breast carcinoma were included. HER-2 expression was determined by routine clinical laboratory assessment, and tumors with 3 + immunohistochemistry staining intensity or gene amplification by fluorescent in situ hybridization were considered HER-2 positive. Response was assessed by physical examination, imaging assessment, and pathologic assessment at the time of surgery. RESULTS: The median patient age was 45 years. At baseline, 68% of patients had lymph node positive disease, 87% had >/= T2 tumors, and 28% of patients had HER-2 positive tumors. Eighty-four percent of patients received four courses of FAC, 8% of patients received 3 courses of FAC, and the remaining 8% of patients received 5-6 courses of FAC. The clinical response rate (complete response [CR] and partial response [PR]) was 78%, the imaging response rate (CR and PR) was 64%, and 15% of patients had a good pathologic response, defined as a CR or minimal residual disease (tumor measuring < 1 cm in greatest dimension and negative lymph nodes). Concordance between the three methods of response assessment (clinical, pathologic, and imaging) was modest and was best between clinical assessment and imaging assessment (64% concordance). HER-2 status did not correlate with pathologic or clinical response (assessed by physical examination or imaging), although a nonsignificant trend was noted toward better response in patients with breast tumors that overexpressed HER-2. CONCLUSIONS: The authors found no significant correlation between HER-2 expression and clinical or pathologic response to neoadjuvant chemotherapy in patients with breast carcinoma.

Adult↗
PubMed2003

A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb.

The positive transcription elongation factor b (P-TEFb) contains cyclin T1 (CycT1) and cyclin-dependent kinase 9 (Cdk9). For activating the expression of eukaryotic genes, the histidine-rich sequence in CycT1 binds the heptapeptide repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), whereupon Cdk9 phosphorylates the CTD. We found that alanine-substituted heptapeptide repeats that cannot be phosphorylated also bind CycT1. When placed near transcription units, these CTD analogs block effects of P-TEFb. Remarkably, the transcriptional repressor PIE-1 from Caenorhabditis elegans behaves analogously. It binds CycT1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation. Thus, our findings reveal a new mechanism by which repressors inhibit eukaryotic transcription.

Alanine↗
PubMed2003

Cloning and expression of a novel, truncated, progesterone receptor.

Progesterone acts via two specific receptors to affect gene transcription in target tissues. Progesterone receptor (PR) B contains 933 amino acids while PR A is a truncated version lacking the initial 164 amino acids. We have cloned a novel, truncated PR from both human adipose and aortic cDNA libraries. This cDNA encodes a predicted protein of 314 amino acids, termed PR-M. Initiation of transcription of PR-M occurs in intron 3, with the initial exon identical to exon 4 of the genomic PRs, except for a novel 16 amino acid amino-terminal sequence, consistent with a signal peptide. The remainder of PR-M is identical to the genomic PR. Transcript for this protein was identified by RT-PCR in human aortic endothelial cells and T47D breast cancer cells. Expression of PR-M in Sf 9 insect cells results in a 38-kDa protein, demonstrated in human aortic endothelial cells and T47D breast cancer cells. The function of PR-M remains to be determined. The presence of a signal peptide and the lack of a DNA binding region suggests a non-genomic action.

Adipose Tissue↗
PubMed2003

Grazing-incidence x-ray diffraction study of Langmuir films of amphiphilic monodendrons.

We have used pressure-area isotherms and grazing-incidence x-ray diffraction to study structures of Langmuir films of first-generation monodendrons with two or three peripheral alkyl chains. Unlike the structures observed in their bulk liquid crystalline mesophases, these multichain monodendrons form either a centered rectangular lattice with molecular axes tilted toward nearest neighbors or an oblique lattice with molecular axes tilted in low-symmetry directions.

Journal Article↗
PubMed2003

Domains of eIF1A that mediate binding to eIF2, eIF3 and eIF5B and promote ternary complex recruitment in vivo.

Translation initiation factor 1A (eIF1A) is predicted to bind in the decoding site of the 40S ribosome and has been implicated in recruitment of the eIF2-GTP-Met-tRNA i Met ternary complex (TC) and ribosomal scanning. We show that the unstructured C-terminus of eIF1A interacts with the C-terminus of eIF5B, a factor that stimulates 40S-60S subunit joining, and removal of this domain of eIF1A diminishes translation initiation in vivo. These findings support the idea that eIF1A-eIF5B association is instrumental in releasing eIF1A from the ribosome after subunit joining. A larger C-terminal truncation that removes a 3(10) helix in eIF1A deregulates GCN4 translation in a manner suppressed by overexpressing TC, implicating eIF1A in TC binding to 40S ribosomes in vivo. The unstructured N-terminus of eIF1A interacts with eIF2 and eIF3 and is required at low temperatures for a step following TC recruitment. We propose a modular organization for eIF1A wherein a core ribosome-binding domain is flanked by flexible segments that mediate interactions with other factors involved in recruitment of TC and release of eIF1A at subunit joining.

Binding Sites↗