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Biomedical subjects

Jie Fan

Publications and source records attributed to Jie Fan.

33 records · Page 2Linked to original sources
PubMed2003

One-step nanocasting synthesis of highly ordered single crystalline indium oxide nanowire arrays from mesostructured frameworks.

A one-step nanocasting route has been demonstrated to prepare highly ordered single-crystal indium oxide nanowire (IONW) arrays with mesostructured frameworks. Unlike the reported multistep nanocasting process (synthesis of mesoporous materials, and then incorporation of precursors and formation of inorganic frameworks), a highly ordered mesostructured surfactant-silica monolith with low external surface serves as both the template and the reducing agent and makes the formation of single-crystal IONWs in its channels easily in one step by using normal In(NO(3))(3) as an inorganic precursor. After silica is removed, highly ordered uniform single-crystal IONW arrays with hexagonal (p6mm) or cubic (Ia3d) mesostructures are derived. These new materials are studied by XRD, SEM, TEM, N(2) adsoption, and UV spectrum. Furthermore, this one-step nanocasting synthesis route is a generalized method and can be used to synthesized a highly ordered mesoporous silica monolith with metal oxide nanocrystals in its channels. To the best of our knowledge, this is the first report of a single crystalline mesostructured In(2)O(3) framework.

Journal Article↗
PubMed2003

Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors.

Polymorphonuclear leukocytes (PMNs) are critical effector cells of the innate immune system that protect the host by migrating to inflammatory sites and killing pathogenic microbes. We addressed the role of chemokine receptor desensitization induced by G-protein-coupled receptor kinases (GRKs) in the feedback control of PMN migration. We show that the chemokine macrophage inflammatory protein-2 (MIP-2) induces GRK2 and GRK5 expression in PMNs through phosphoinositide-3-kinase (PI3K)-gamma signaling. We also show that lipopolysaccharide (LPS)-activated signaling through the Toll-like receptor (TLR)-4 pathway transcriptionally downregulates the expression of GRK2 and GRK5 in response to MIP-2. The reduced expression of GRKs lowers chemokine receptor desensitization and markedly augments the PMN migratory response. These data indicate that TLR4 modulation of PMN surface chemokine receptor expression subsequent to the downregulation of GRK2 and GRK5 expression is a critical determinant of PMN migration.

Animals↗
PubMed2003

Self-adjusted synthesis of ordered stable mesoporous minerals by acid-base pairs.

Although the chemical diversity of ordered composite mesoporous materials has been expanding during the past decade, progress has been limited by the need for a general synthetic approach that is predictive and makes use of well developed fundamental chemical principles. Researchers have previously used the interaction of organic-inorganic (OI) species that are present during the nucleation of the composite phase, and several synthesis pathways, such as direct surfactant-inorganic interaction (S+I-, S-I+, S0I0) and mediated interaction (S+X-I+, S-X+I-), have been proposed. Here we describe a new perspective in which the self-adjusted inorganic-inorganic (II) interplay between two or more inorganic precursors is guided by acid-base chemistry considerations, and in this simple way we produce an overall 'framework' for the sophisticated combination of synergic inorganic acid-base precursor pairs. We propose several new routes and demonstrate their versatility and validity through the successful syntheses of a wide variety of highly ordered, large-pore, homogeneous, stable and multicomponent mesostructured minerals, including metal phosphates and metal borates, as well as various metal oxides and mixed metal oxides. We show that the highly ordered mesostructured metal phosphates can be moulded into morphologies of choice, and that they show interesting physicochemical properties.

Acids↗
PubMed2003

TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase.

Interactions of polymorphonuclear neutrophils (PMNs) with endothelial cells may contribute to the activation of endothelial cell responses involved in innate immunity. We explored a novel function of PMN NADPH oxidase in the mechanism of Toll-like receptor-2 (TLR2) upregulation induced by LPS-TLR4 signaling in endothelial cells. We showed that LPS induced TLR2 up-regulation through TLR4- and MyD88-dependent signaling. In neutropenic mice, the LPS-induced NF-kB activation and TLR2 expression were significantly reduced, and both responses were restored upon repletion by PMN obtained from WT mice but not by PMNs from NADPH oxidase gp91pho(-/-) mice. These findings were recapitulated in mouse lung vascular endothelial cells cocultured with PMNs, indicating that the augmented NF-kB activation and the resultant TLR2 upregulation in endothelial cells were secondary to oxidant signaling generated by PMN NADPH oxidase. The functional relevance of NADPH oxidase in mediating TLR4-induced TLR2 expression in endothelial cells was evident by markedly elevated and stable ICAM-1 expression as well as augmented PMN migration in response to sequential challenge with LPS and peptidoglycan. Thus, PMN NADPH oxidase-derived oxidant signaling is an important determinant of the cross talk between TLR4 and TLR2 and the control of endothelial cell activation.

Animals↗
PubMed2003

Significance of expression of heat shock protein90alpha in human gastric cancer.

AIM: To evaluate the significance of hsp90alpha expression in human gastric cancer tissues. METHODS: Immunohistochemical staining was used in clinical specimens from 33 cases of gastric cancer and 33 cases of gastritis with rabbit anti-human hsp90alpha multi-clonal antibody in order to explore the relationship between the expression of hsp90alpha in gastric carcinoma tissue and gastritis tissue as well as in mucous membrane adjacent to cancer and lymph node metastasis. RESULTS: Hsp90alpha was detected in 88% of gastric carcinoma cases and 55% of gastritis cases. The hsp90alpha positive rate in gastric cancer group was significantly higher than that in gastritis group (P<0.01, P=0.005). The hsp90alpha positive rate in gastric cancer and in mucous membrane adjacent to cancer was 88% and 55% respectively (P<0.01, P=0.005). The hsp90alpha positive rate in lymph node metastasis group and non-lymph node metastasis group was 100% and 60% respectively, and a significant correlation between hsp90alpha expression and lymph node metastasis was shown (P<0.01, P=0.005). CONCLUSION: The hsp90alpha expression rate in gastric cancer group was significantly higher than that in gastritis group as well as that in the group of mucous membrane adjacent to cancer. The hsp90alpha expression in lymphatic node metastasis group was higher than that in non-lymphatic node metastasis group. The results indicate that increased hsp90alpha expression has a close relationship with occurrence and lymph node metastasis of gastric cancer.

Biomarkers, Tumor↗
PubMed2003

[The treatment of benign prostatic hyperplasia by means of transurethral holmium laser enucleation].

OBJECTIVES: To evaluate the clinical effect of the holmium laser enucleation and morcellation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia(BPH). METHODS: In the treatment of 35 BPH patients, 100 watt high-powered holmium laser set was used transurethrally and a reciprocating blade tissue morcellator was introduced via a nephroscope to enucleate and morcellate the prostatic tissue. RESULTS: Operations in all 35 cases were successful. The average operation time was 60 +/- 23.2 (range 30-180) min. The removed prostatic tissue weighed 31 +/- 9 (range 10-56) g on average. The average catheter time was 1.5 d (from 20 h to 4 d). No blood transfusion was performed in all cases. Histopathological analysis confirmed the diagnosis of BPH in all cases. In the 3-month follow up of 32 cases, IPSS dropped from 24 +/- 6.2 to 5.6 +/- 3.6; the peak urinary flow rate(Qmax) went up from 8.5 +/- 3.9 ml/s to 22.0 +/- 7.2 ml/s; the residual volume of urine dropped from 138 +/- 125 ml to 21 +/- 15 ml. No serious complications were found. CONCLUSIONS: HoLEP is effective in treating BPH. It can completely enucleate the hyperplastic tissue with little bleeding in operation. The treatment has the advantages of short catheter time and significant clinical improvements.

Aged↗
PubMed2002

Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic shock and lipopolysaccharide.

The Toll-like receptor 4 (TLR4) has recently been shown to function as the major upstream sensor for LPS. In this study, a rodent model of lung injury following resuscitated hemorrhagic shock was used to examine the regulation of TLR4 gene and protein expression in vivo and in vitro. Intratracheal LPS alone induced a rapid reduction in whole lung TLR4 mRNA, an effect which is also observed in recovered alveolar macrophages. This effect appeared to be due to a lowering of TLR4 mRNA stability by approximately 69%. By contrast, while shock/resuscitation alone had no effect on TLR4 mRNA levels, it markedly altered the response to LPS. Specifically, antecedent shock prevented the LPS-induced reduction in TLR4 mRNA levels. This reversal was explained by the ability of prior resuscitated shock both to prevent the destabilization of TLR4 mRNA by LPS and also to augment LPS-stimulated TLR4 gene transcription compared with LPS alone. Oxidant stress related to shock/resuscitation appeared to contribute to the regulation of TLR4 mRNA, because supplementation of the resuscitation fluid with the antioxidant N-acetylcysteine reversed the ability of shock/resuscitation to preserve TLR4 mRNA levels following LPS. TLR4 protein levels in whole lung mirrored the changes seen for TLR4 mRNA. Considered in aggregate, these data suggest that levels of tlr4 expression are controlled both transcriptionally as well as posttranscriptionally through altered mRNA stability and that antecedent shock/resuscitation, a form of global ischemia/reperfusion, might influence regulation of this gene.

Animals↗
PubMed2002

Nonionic block copolymer synthesis of large-pore cubic mesoporous single crystals by use of inorganic salts.

Large-pore cubic (Im3m) mesoporous silica single crystals have been synthesized by using commercial nonionic block copolymers as templates and inorganic salts as additives. These single crystals possess exclusively uniform rhombdodecahedron shapes ( approximately 1 mum) with approximately 100% yield. The mesopore lattice array in each crystal face is solved by TEM, further confirming that these crystals are perfect single crystals.

Journal Article↗
PubMed2002

Dissection of a complex enhancer element: maintenance of keratinocyte specificity but loss of differentiation specificity.

In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5' upstream regulatory sequence known to faithfully recapitulate the strong endogenous keratin 5 (K5) promoter and/or enhancer activity. One of these, DNase I-hypersensitive site (HSs) 4, was unique in that it acted independently to drive abundant and keratinocyte-specific reporter gene activity in culture and in transgenic mice, despite the fact that it was not essential for K5 enhancer activity. We have identified evolutionarily conserved regulatory elements and a number of their associated proteins that bind to this compact and complex enhancer element. The 125-bp 3' half of this element (referred to as 4.2) is by far the smallest known strong enhancer element possessing keratinocyte-specific activity in vivo. Interestingly, its activity is restricted to a subset of progeny of K5-expressing cells located within the sebaceous gland. The other half of HSs 4 (termed 4.1) possesses activity to suppress sebocyte-specific expression and induce expression in the channel (inner root sheath) cells surrounding the hair shaft. Our findings lead us to a view of keratinocyte gene expression which is determined by multiple regulatory modules, many of which contain AP-2 and/or Sp1/Sp3 binding sites for enhancing expression in skin epithelium, but which also harbor one or more unique sites for the binding of factors which determine specificity. Through mixing and matching of these modules, additional levels of specificity are obtained, indicating that both transcriptional repressors and activators govern the specificity.

Animals↗
PubMed2002

Cloning and characterization of a novel all-trans retinol short-chain dehydrogenase/reductase from the RPE.

PURPOSE: In the photic visual cycle, retinal G protein-coupled receptor (RGR) isomerizes all-trans retinal to 11-cis retinal in the retinal pigment epithelium (RPE) after illumination. It is unclear, however, how all-trans retinal, the substrate for RGR, is generated in the RPE, because no all-trans retinol dehydrogenase (atRDH) has been identified in the RPE. This study was conducted to identify the atRDH that generates all-trans retinal in the RPE. METHODS: The full-length cDNA encoding a novel atRDH, RDH10, was cloned by PCR based on an expressed sequence tag (EST). Cellular localization was determined at the mRNA level by Northern blot analysis, RT-PCR, and in situ hybridization and at the protein level by immunohistochemistry with an antibody specific to RDH10. The activity was measured by an RDH activity assay with recombinant RDH10 expressed in COS cells. RESULTS: The full-length RDH10 was cloned from the human, cow, and mouse. These cDNAs encode a protein of 341 amino acids and have significant sequence homology with other short-chain dehydrogenases/reductases (SDRs). The human RDH10 shares 100% and 98.6% amino acid sequence identity with the bovine and mouse proteins, respectively, suggesting a highly conserved sequence during evolution. RDH10 is predominantly expressed in the microsomal fraction of the RPE. Human RDH10 expressed in COS cells oxidized all-trans retinol to all-trans retinal. RDH10 displayed substrate specificity for all-trans retinol and preferred nicotinamide adenine dinucleotide phosphate (NADP) as the cofactor. CONCLUSIONS: RDH10 is a novel retinol oxidase expressed in the RPE. This enzyme can generate all-trans retinal from all-trans retinol and may play an important role in the photic visual cycle.

Alcohol Oxidoreductases↗
PubMed2001

Role of neutrophil NADPH oxidase in the mechanism of tumor necrosis factor-alpha -induced NF-kappa B activation and intercellular adhesion molecule-1 expression in endothelial cells.

In this study, we explored a novel function of polymorphonuclear neutrophils (PMN) NAD(P)H oxidase in the mechanism of tumor necrosis factor-alpha (TNFalpha)-induced NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. Studies were made in mice lacking the p47(phox) subunit of NAD(P)H oxidase as well as in cultured mouse lung vascular endothelial cells (MLVEC) from these mice. In response to TNFalpha challenge, NF-kappaB activation and ICAM-1 expression were significantly attenuated in lungs of p47(phox)(-/-) mice as compared with wild-type (WT) mice. The attenuated NF-kappaB activation in p47(phox)(-/-) mice was secondary to inhibition of NIK activity and subsequent IkappaBalpha degradation. Induction of neutropenia using anti-PMN serum prevented the initial TNFalpha-induced NF-kappaB activation and ICAM-1 expression in WT mice, indicating the involvement of PMN NAD(P)H oxidase in signaling these responses. Moreover, the responses were restored upon repletion with PMN obtained from WT mice but not with PMN from p47(phox)(-/-) mice. These findings were recapitulated in MLVEC co-cultured with PMN, suggesting that NF-kappaB activation and resultant ICAM-1 expression in endothelial cells occurred secondary to oxidants generated by the PMN NAD(P)H oxidase complex. The functional relevance of the PMN NAD(P)H oxidase in mediating TNFalpha-induced ICAM-1-dependent endothelial adhesivity was evident by markedly reduced adhesion of p47(phox)(-/-) PMN in co-culture experiments. Thus, oxidant signaling by the PMN NAD(P)H oxidase complex is an important determinant of TNFalpha-induced NF-kappaB activation and ICAM-1 expression in endothelial cells.

Animals↗
PubMedDate not supplied

9-cis Retinal increased in retina of RPE65 knockout mice with decrease in coat pigmentation.

The protein RPE65 is essential for the generation of the native chromophore, 11-cis retinal, of visual pigments. However, the Rpe65 knockout (Rpe65-/-) mouse shows a minimal visual response due to the presence of a pigment, isorhodopsin, formed with 9-cis retinal. Isorhodopsin accumulates linearly with prolonged dark-rearing of the animals. The majority of Rpe65-/- mice have an agouti coat color. A tan coat color subset of Rpe65-/- mice was found to have an enhanced visual response as measured by electroretinograms. The enhanced response was found to be due to increased levels of 9-cis retinal and isorhodopsin pigment levels. Animals of both coat colors reared in cyclic light have minimal levels of regenerated pigment and show photoreceptor degeneration. On dark-rearing, pigment accumulates and photoreceptor degeneration is decreased. In the tan Rpe65-/- mice, the level of photoreceptor degeneration is less than in the agouti animals, which have an increased pigment and decreased free opsin level. Therefore, photoreceptor damage correlates with the amount of the apoprotein present, supporting findings that the activity from unregenerated opsin can lead to photoreceptor degeneration.

Animals↗