PubMed Health⌕ Search

Biomedical subjects

Min Lu

Publications and source records attributed to Min Lu.

105 records · Page 6Linked to original sources
PubMed2002

Prostaglandin E(2) stimulates prostatic intraepithelial neoplasia cell growth through activation of the interleukin-6/GP130/STAT-3 signaling pathway.

Cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) secretion are increased in prostatic intraepithelial neoplasia (PIN) and prostate cancer. PGE(2) biosynthesis by cyclooxygenase (COX)-2 plays a pivotal role in inflammation and carcinogenesis. One of the critical proinflammatory cytokines in the prostate is interleukin-6 (IL-6). We hypothesized that increased expression of COX-2, with resultant increased levels of PGE(2) in human PIN cells, activates the IL-6 signaling pathway. We demonstrate an autocrine upregulation of PGE(2) mediated by IL-6 in a human PIN cell line. We further demonstrate that PGE(2) stimulates soluble IL-6 receptor (sIL-6R) release, gp130 dimerization, Stat-3 protein phosphorylation, and DNA binding activity. These events, induced by PGE(2), lead to increased PIN cell growth. Treatment of PIN cells with a selective COX-2 inhibitor decreases cell growth. Finally, PGE(2)-stimulated PIN cell growth was abrogated by the addition of IL-6 neutralizing antibodies. These data provide mechanistic evidence that increased expression of COX-2/PGE(2) contributes to prostate cancer development and progression via activation of the IL-6 signaling pathway.

Antigens, CD↗
PubMed2002

Discovery of sonic hedgehog expression in postnatal growth plate chondrocytes: differential regulation of sonic and Indian hedgehog by retinoic acid.

Sonic hedgehog (Shh) is a key signal protein in early embryological patterning of limb bud development. Its analog, Indian hedgehog (Ihh), primarily expressed during early cartilage development in prehypertrophic chondrocytes, regulates proliferation and suppresses terminal differentiation of postnatal growth plate (GP) chondrocytes. We report here for the first time that both Shh and Ihh mRNA are expressed in the GP of rapidly growing 6-week-old broiler-strain chickens. They are also expressed in other tissues such as articular chondrocytes, kidney, and bone. In situ hybridization and RT-PCR analyses reveal Shh in all zones of the GP, with peak expression in late hypertrophy. Using primary cultures of GP chondrocytes in serum-containing medium, we followed the patterns of Shh and Ihh mRNA expression as the cultures matured and mineralized. We find a cyclical expression of both hedgehog genes during the early period of culture development between day 10 and 14; when one is elevated, the other tended to be suppressed, suggesting that the two hedgehogs may play complementary roles during GP development. Retinoic acid (RA), a powerful modulator of gene expression in cell differentiation, stimulates GP chondrocytes toward terminal differentiation, enhancing mineral formation. We find that RA strongly suppresses Ihh, but enhances expression of Shh in this system. While Ihh suppresses maturation of GP chondrocytes to hypertrophy, we hypothesize that Shh acts to push these cells toward hypertrophy.

Animals↗
PubMed2002

Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice.

Restenosis remains a major cause of morbidity and mortality after coronary angioplasty. Injury-induced inflammation, thrombosis, smooth muscle cell (SMC) proliferation, and neointimal formation contribute to restenosis. These events are linked to circulating glucose-derived advanced gycation endproducts (AGE), known to promote cell proliferation, lipid glycoxidation and oxidant stress. This study evaluates the association between dietary AGE content and neointimal formation after arterial injury in genetically hypercholesterolemic mice. Male, 12-week-old, apolipoprotein E-deficient (apoE(-/-)) mice were randomly assigned to receive either a high AGE diet (HAD; AGE=15000 U/mg), or a similar diet with ten-fold lower AGE (LAD; AGE=1500 U/mg). These mice underwent femoral artery injury 1 week later, and were maintained on their diets for an additional 4 weeks. At 4 weeks after injury, significant decrease in neointimal formation was noted in LAD-fed mice. Neointimal area, intima/media ratio, and stenotic luminal area (LA) were less pronounced in the LAD group than the HAD group (P<0.05). These quantitative differences were associated with a marked reduction ( approximately 56%) of macrophages in the neointimal lesions, as well as an obvious reduction of SMC content of LAD-fed mice. The reduction of neointimal formation in the LAD mice correlated with a approximately 40% decrease in circulating AGE levels (P<0.0005). Immunohistochemistry also showed a reduced ( approximately 1.5-fold) deposition of AGE in the endothelia, SMC, and macrophages in neointimal lesions of LAD-fed mice. These results represent the first evidence in vivo for a causal relationship between dietary AGE and the vessel wall response to acute injury, suggesting a significant potential for dietary AGE restriction in the prevention of restenosis after angioplasty.

Animals↗
PubMed2002

Genetic evidence that interhelical packing interactions in the gp41 core are critical for transition of the human immunodeficiency virus type 1 envelope glycoprotein to the fusion-active state.

The envelope glycoprotein complex (gp120-gp41) of human immunodeficiency virus type 1 (HIV-1) promotes the fusion of viral and cellular membranes through formation of the fusion-active six-helix bundle in the gp41 ectodomain. This gp41 core structure consists of three C-terminal helices packed in an antiparallel manner into hydrophobic grooves on the surface of the N-terminal trimeric coiled coil. Alanine mutations that destabilize the N- and C-terminal interhelical packing interactions also reduce viral infectivity. Here we show that viruses bearing these mutations exhibit a marked potentiation of inhibition by peptides that make up the gp41 core. By contrast, these viruses are unchanged in their sensitivities to soluble CD4, the CXCR4 coreceptor ligand SDF-1alpha, and human anti-HIV immunoglobulin, reagents that impact the initial, receptor-induced conformational changes in the envelope glycoprotein. Our results support the notion that these alanine mutations specifically affect the conformational transition to the fusion-active gp41 structure. The mutations also increase viral sensitivity to the gp41-directed monoclonal antibody 2F5, suggesting that this broadly neutralizing antibody may also interfere with this transition. The conformational activation of the HIV-1 envelope glycoprotein likely represents a viable target for vaccine and antiviral drug development.

Amino Acid Sequence↗
PubMed2002

Oligomeric and conformational properties of a proteolytically mature, disulfide-stabilized human immunodeficiency virus type 1 gp140 envelope glycoprotein.

We describe the further properties of a protein, designated SOS gp140, wherein the association of the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is stabilized by an intersubunit disulfide bond. HIV-1(JR-FL) SOS gp140, proteolytically uncleaved gp140 (gp140(UNC)), and gp120 were expressed in stably transfected Chinese hamster ovary cells and analyzed for antigenic and structural properties before and after purification. Compared with gp140(UNC), SOS gp140 reacted more strongly in surface plasmon resonance and radioimmunoprecipitation assays with the neutralizing monoclonal antibodies (MAbs) 2G12 (anti-gp120), 2F5 (anti-gp41), and 17b (to a CD4-induced epitope that overlaps the CCR5-binding site). In contrast, gp140(UNC) displayed the greater reactivity with nonneutralizing anti-gp120 and anti-gp41 MAbs. Immunoelectron microscopy studies suggested a model for SOS gp140 wherein the gp41 ectodomain (gp41(ECTO)) occludes the "nonneutralizing" face of gp120, consistent with the antigenic properties of this protein. We also report the application of Blue Native polyacrylamide gel electrophoresis (BN-PAGE), a high-resolution molecular sizing method, to the study of viral envelope proteins. BN-PAGE and other biophysical studies demonstrated that SOS gp140 was monomeric, whereas gp140(UNC) comprised a mixture of noncovalently associated and disulfide-linked dimers, trimers, and tetramers. The oligomeric and conformational properties of SOS gp140 and gp140(UNC) were largely unaffected by purification. An uncleaved gp140 protein containing the SOS cysteine mutations (SOS gp140(UNC)) was also oligomeric. Surprisingly, variable-loop-deleted SOS gp140 proteins were expressed (although not yet purified) as cleaved, noncovalently associated oligomers that were significantly more stable than the full-length protein. Overall, our findings have relevance for rational vaccine design.

Animals↗
PubMed2002

Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1.

The envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 has evolved a structure that is minimally immunogenic while retaining its natural function of receptor-mediated virus-cell fusion. The Env complex is trimeric; its six individual subunits (three gp120 and three gp41 subunits) are associated by relatively weak, noncovalent interactions. The induction of neutralizing antibodies after vaccination with individual Env subunits has proven very difficult, probably because they are inadequate mimics of the native complex. Our hypothesis is that a stable form of the Env complex, perhaps with additional modifications to rationally alter its antigenic structure, may be a better immunogen than the individual subunits. A soluble form of Env, SOS gp140, can be made that has gp120 stably linked to the gp41 ectodomain by an intermolecular disulfide bond. This protein is fully cleaved at the proteolysis site between gp120 and gp41. However, the gp41-gp41 interactions in SOS gp140 are too weak to maintain the protein in a trimeric configuration. Consequently, purified SOS gp140 is a monomer (N. Schülke, M. S. Vesanen, R. W. Sanders, P. Zhu, D. J. Anselma, A. R. Villa, P. W. H. I. Parren, J. M. Binley, K. H. Roux, P. J. Maddon, J. P. Moore, and W. C. Olson, J. Virol. 76:7760-7776, 2002). Here we describe modifications of SOS gp140 that increase its trimer stability. A variant SOS gp140, designated SOSIP gp140, contains an isoleucine-to-proline substitution at position 559 in the N-terminal heptad repeat region of gp41. This protein is fully cleaved, has favorable antigenic properties, and is predominantly trimeric. SOSIP gp140 trimers are noncovalently associated and can be partially purified by gel filtration chromatography. These gp140 trimers are dissociated into monomers by anionic detergents or heat but are relatively resistant to nonionic detergents, high salt concentrations, or exposure to a mildly acidic pH. SOSIP gp140 should be a useful reagent for structural and immunogenicity studies.

Amino Acid Sequence↗
PubMed2002

Shear stress activation of SREBP1 in endothelial cells is mediated by integrins.

We investigated the effect of shear stress on the sterol regulatory element-binding protein 1 (SREBP1) in vascular endothelial cells (ECs) and the mechanotransduction mechanism involved. Application of a shear stress (12 dyn/cm(2)) caused the proteolytic cleavage of SREBP1 and the ensuing translocation of its transcription factor domain into the nucleus. As a result, shear stress increased the mRNAs encoding the low density lipoprotein receptor (LDLR), as well as the binding of (125)I-LDL. Using a step flow channel, we showed that SREBP1 activation in ECs under laminar flow is transient, but disturbed flow causes sustained activation. In studying the shear stress-elicited molecular signaling that activates SREBP1, we found that blocking the beta(1)-integrin with the AIIB2 blocking-type monoclonal antibody inhibited SREBP1 activation induced by shear stress. EC attachment to fibronectin or the activation of beta(1)-integrin in the suspended ECs by the TS2/16 monoclonal antibody was sufficient for SREBP1 activation. Furthermore, transient transfection assays showed that dominant-negative mutants of focal adhesion kinase and c-Src attenuated the shear stress-increased LDLR promoter activity. These results demonstrate that integrin signaling plays a critical role in the modulation of SREBP in ECs in response to shear stress.

Animals↗
PubMed2002

Synthesis and insecticidal activity of novel 4beta-halogenated benzoylamino podophyllotoxins against Pieris rapae Linnaeus.

Twelve new 4beta-halogenated benzoylamino compounds (7.1-7.12) of podophyllotoxin have been synthesized, and their structures were confirmed by IR, 1H-NMR, MS spectra as well as CHN elemental analysis. These compounds showed delayed insecticidal activity against 5th instar larvae of Pieris rapae Linnaeus in vivo, when tested by a leaf-dipping method at a concentration of 250ppm. By preliminary qualitative structure-activity relationship analysis, we found the following results: 1) Compounds 7.2, 7.5-7.9 were more potent than the nature parent product in the mortality after 15 d against P. rapae in vivo. Especially compounds 7.5 and 7.6 bearing meta- and para-chlorobenzene substituents respectively, were the most potent of these compounds; 2) Substitution on the benzene ring moiety of 4beta-benzoylamino podophyllotoxin (PPT) with Cl, Br, I at the para or at the meta position yielded compounds which were as potent or more potent than those containing the corresponding substituting group at the ortho position. 3) Substitution on the benzene ring moiety of 4beta-benzoylamino podophyllotoxin with I either at the ortho, meta or para position yielded less potent compounds (7.10-7.12) when compared with PPT.

Animals↗
PubMed2002

Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo.

Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analogue of vitamin E, is a strong inducer of apoptosis, whereas alpha-tocopherol (alpha-TOH) lacks apoptogenic activity (J. Neuzil et al., FASEB J., 15: 403-415, 2001). Here we investigated the possible antineoplastic activities of alpha-TOH and alpha-TOS and further explored the potential of alpha-TOS as an antitumor agent. Using nude mice with colon cancer xenografts, we found that alpha-TOH exerted modest antitumor activity and acted by inhibiting tumor cell proliferation. In contrast, alpha-TOS showed a more profound antitumor effect, at both the level of inhibition of proliferation and induction of tumor cell apoptosis. alpha-TOS was nontoxic to normal cells and tissues, triggered apoptosis in p53(-/-) and p21(Waf1/Cip1(-/-)) cancer cells, and exerted a cooperative proapoptotic activity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) due to differences in proapoptotic signaling. Finally, alpha-TOS cooperated with tumor necrosis factor-related apoptosis-inducing ligand in suppression of tumor growth in vivo. Vitamin E succinate is thus a potent and highly specific anticancer agent and/or adjuvant of considerable therapeutic potential.

Animals↗
PubMed2002

Curative effect of wilsonii injecta on severe head injury.

OBJECTIVE: To study the curative effect of wilsonii injecta on severe head injury (SHI). METHODS: A total of 120 patients with SHI were divided randomly into 2 groups, the patients treated with conventional methods as Group A (n=60) and the patients treated with wilsonii injecta as Group B (n=60). The changes of neural function indexes were evaluated with Glasgow Coma Scale (GCS) before treatment and with Glasgow Outcome Scale (GOS) after treatment, simultaneously, the parameters of hemorrheological indexes (HI), brain electrical activity map (BEAM) and transcranial Doppler sonography (TCD) were observed before and after treatment. RESULTS: In Group B, the clinical GCS, the HI, the BEAM and the prognosis GOS were improved much more than those in Group A. And the TCD parameters in Group B decreased, which had significant difference compared with that in Group A (P<0.01). CONCLUSIONS: Wilsonii injecta can rapidly improve the injured p ersons' conscious states, the abnormal BEAM and the surviving quality. It suggests that the improvement of the HI is related to the relief of the vasospasm of the arterial blood vessels in the brain, which may be one of the important mechanisms of wilsonii injecta in improving the prognosis.

Adult↗
PubMed2002

Repair effect of Schwann cells modified by microgene pSVPoMcat on injured spinal cord in rats.

OBJECTIVE: To observe the repair effect of Schwann cells (SCs) modified by microgene pSVPoMcat on injured spinal cord in rats. METHODS: Semi-transection injury at the level of T(8) of spinal cord was made with cutting method on 120 Sprague Dawley (SD) rats. Then 40 rats implanted with SCs modified by microgene pSVPoMcat were taken as Group A, 40 rats implanted with simple SCs as Group B and the other 40 rats were taken as the control group (Group C). The functional recovery of the rats was observed through combined behavioral score (CBS) and cortical somatosensory evoked potential (CSEP), and the expression of the glial fibrillary acidic protein (GFAP) was measured with in situ hybridization and immunocytochemistry. At 3 months after operation, the rats were examined with magnetic resonance image (MRI), and the neurofilaments (NF) of the axons were stained with immunohistochemical method. RESULTS: GFAP expression in Group A was significantly lower than that of the other 2 groups. MRI showed that the spinal signals in the injured area recovered fundamentally in Group A, didn't recover in Group B and malacia focus was found in Group C, which was same as the results of NF staining. Wave amplitudes in incubation periods in Group A and Group B tended to recover. It recovered to the normal level in Group A, which was similar to the results of CBS. CONCLUSIONS: SCs modified by microgene pSVPoMcat can inhibit GFAP expression, improve the growth of the axons and the functional recovery of neurons after spinal cord injury.

Analysis of Variance↗
PubMed2002

[Assessing indices of container seedling quality].

In this paper, the assessing indices of container seedlings quality were synthesized in accordance with growth and physiological factors. The results showed that the seedling quality might be determined by the dormancy state of terminal bud, nutrient condition of plant, and the state of root system. The critical quality indices should include stem diameter at soil surface, dry weight of terminal bud, and soluble sugar content. Moreover, some indices such as root system vitality and dry weight of plant were also important.

Plant Development↗
PubMed2002

[Inter-population and inter-individual effect of education attainment on men's behavior of smoking: China multi-center study of cardiovascular epidemiology].

OBJECTIVE: To study the inter-population and inter-individual effect of education attainment on men's behavior of smoking in China. METHOD: A cross-sectional study of 7,415 men, aged 35-59 years, from 15 population samples was carried out in 1998. Information on education attainment and smoking was collected by standardized questionnaires. The population samples were divided into 2 groups according to the proportion of men with college or above education attainment: group I had an average 25.8% of men with college or above education attainment, and group II had an average 2.0% of men with college or above education attainment. RESULTS: (1) In group I, the percent of ever smokers, current smokers, deeper smoker, and ever smokers with cessation due to disease and the average number of cigarettes per day for the smokers were significantly lower than in group II (66.2%, 56.4%, 34.4%, 47.8%, 17.2 cigarettes/day vs 75.8%, 64.4%, 40.3%, 58.4%, 20.4 cigarettes/day, respectively). (2) The percent of current smokers and the number of cigarettes decreased with increased education attainment in both groups. Taking the men with college or above education attainment in group I as reference, the odd ratio of smoking for those with high school education in group I was 1.8 (95% CI: 1.5-2.1), for those with middle school or lower education in group I was 2.0(95% CI: 1.7-2.5), for those with college or above education in group II was 1.4(95% CI: 0.9-2.1), for those with high school education in group II was 1.7(95% CI: 1.4-2.1), and for those with middle school or lower education in group II was 2.4 (95% CI: 2.1-2.8). CONCLUSION: Smoking behavior was affected by both individual education attainment and population education level. Smoking cessation measures should be focused on the development of better anti-smoking environment, such as education development, health promotion, etc.

Adult↗
PubMed2002

[The CXC-chemokine platelet factor 4 (PF4) increases KG1a cells adherence and modulates actin polymerization of KG1a cells].

OBJECTIVE: To study the effects on adherence of hematopoietic stem/progenitor cells, PF4 was assessed alone or in combination with IL-3 for effects on the total adherence and various kinds of adhesion molecules of KG1a cells as well as actin polymerization in KG1a cells. METHODS: The total adherence was assayed by crystal violet dye staining. The adhesion molecule expression was determined by FACS analysis. These adhesion molecule monoclonal antibodies individually blocked total adherence by MTT. F-actin content was monitored by fluorospectrophotometry. RESULTS: 100 ng/ml PF4 could increase the total adherence of KG1a cells by 80%. 20 ng/ml IL-3 could increase the total adherence of KG1a cells by 96%. When PF4 and IL-3 were combined, the total adherence could be promoted by 97%. Exposure of 1 x 10(6) cells/ml of KG1a cells to 100 ng/ml PF4 the increased total adherence of KG1a cells was mediated by PECAM-1 (CD31), CD44, LFA-1 (CD11a) and Mac-1 (CD11b) but not by P-selectin (CD62P) and E-selectin (CD62E). These adhesion molecule monoclonal antibodies could individually block total adherence for 34%-43%. Similar phenomenon was observed when IL-3 was added onto KG1a cells. Further study found that PF4 induced actin polymerization of KG1a cells. CONCLUSIONS: Our study indicated that PF4 promoted total adherence, as well as several adhesion molecule expression and actin polymerization of KG1a cells. The results suggest that PF4 may have therapeutic utility along with other cytokines by enhancing the total adhesion of hematopoietic stem/progenitor cells to promote the homing.

Actins↗