Biomedical subjects

Jun Li

Publications and source records attributed to Jun Li.

At least 163 records · Page 9Linked to original sources

PubMed2006

Protein kinase C activation and its role in kidney disease.

Protein kinase C (PKC) comprises a superfamily of isoenzymes, many of which are activated by cofactors such as diacylglycerol and phosphatidylserine. In order to be capable of activation, PKC must first undergo a series of phosphorylations. In turn, activated PKC phosphorylates a wide variety of intracellular target proteins and has multiple functions in signal transduced cellular regulation. A role for PKC activation had been noted in several renal diseases, but two that have had most investigation are diabetic nephropathy and kidney cancer. In diabetic nephropathy, an elevation in diacylglycerol and/or other cofactor stimulants leads to an increase in activity of certain PKC isoforms, changes that are linked to the development of dysfunctional vasculature. The ability of isoform-specific PKC inhibitors to antagonize diabetes-induced vascular disease is a new avenue for treatment of this disorder. In the development and progressive invasiveness of kidney cancer, increased activity of several specific isoforms of PKC has been noted. It is thought that this may promote the kidney cancer's inherent resistance to apoptosis, in natural regression or after treatments, or it may promote the invasiveness of renal cancers via cellular differentiation pathways. In general, however, a more complete understanding of the functions of individual PKC isoforms in the kidney, and development or recognition of specific inhibitors or promoters of their activation, will be necessary to apply this knowledge for treatment of cellular dysregulation in renal disease.

Carcinoma, Renal Cell↗

PubMed2006

A mosquito-specific protein family includes candidate receptors for malaria sporozoite invasion of salivary glands.

We describe a previously unrecognized protein family from Aedes and Anopheles mosquitoes, here named SGS proteins. There are no SGS homologues in Drosophila or other eukaryotes, but SGS presence in two mosquito genera suggests that the protein family is widespread among mosquitoes. Ae. aegypti aaSGS1 mRNA and protein are salivary gland specific, and protein is localized in the basal lamina covering the anatomical regions that are preferentially invaded by malaria sporozoites. Anti-aaSGS1 antibodies inhibited sporozoite invasion into the salivary glands in vivo, confirming aaSGS1 as a candidate sporozoite receptor. By homology to aaSGS1 we identified the complete complement of four SGS genes in An. gambiae, which were not recognized in the genome annotation. Two An. gambiae SGS genes display salivary gland specific expression like aaSGS1. Bioinformatic analysis predicts that SGS proteins possess heparin-binding domains, and have among the highest density of tyrosine sulphation sites of all An. gambiae proteins. The major sporozoite surface proteins (CS and TRAP) also bind heparin, and interact with sulphoconjugates during liver cell invasion. Thus, we speculate that sporozoite invasion of mosquito salivary glands and subsequently the vertebrate liver may share similar mechanisms based on sulphation. Phylogenomic analysis suggests that an SGS ancestor was involved in a lateral gene transfer.

Aedes↗

PubMed2006

Multiple-image radiography for human soft tissue.

Conventional radiography only provides a measure of the X-ray attenuation caused by an object; thus, it is insensitive to other inherent informative effects, such as refraction. Furthermore, conventional radiographs are degraded by X-ray scatter that can obscure important details of the object being imaged. The novel X-ray technology diffraction-enhanced imaging (DEI) has recently allowed the visualization of nearly scatter-free images displaying both attenuation and refraction properties. A new method termed multiple-image radiography (MIR) is a significant improvement over DEI, corrects errors in DEI, is more robust to noise and produces an additional image that is entirely new to medical imaging. This new image, which portrays ultra-small-angle X-ray scattering (USAXS) conveys the presence of microstructure in the object, thus differentiating homogeneous tissues from tissues that are irregular on a scale of micrometres. The aim of this study was to examine the use of MIR for evaluation of soft tissue, and in particular to conduct a preliminary investigation of the USAXS image, which has not previously been used in tissue imaging.

Arthrography↗

PubMed2006

A recombinant protein LHRH-PE40 for tumour therapy: preclinical safety studies.

LHRH-PE40, a recombinant DNA-derived protein composed of LHRH and Pseudomonas aeruginosa exotoxin A, is being developed for the treatment of malignant tumours. This experiment was designed to assess its preclinical safety. Reproductive toxicity studies, pharmacokinetic studies, single- and repeat-dose intraperitoneal or intravenous toxicity studies in mice, rats and monkeys were conducted to assess the toxicity of LHRH-PE40. In intravenous single-dose studies in mice, the LD50 was 731.26 microg/kg and 676.03 microg/kg in male and female mice respectively. In single-dose studies and repeat-dose range-finding studies in rats, dose-limited severe vascular leakage syndromes occurred. In repeat-dose long-term studies, except drug-related vascular leakage syndromes, other drug-related changes included decreased testis weight and testis atrophy. In single-dose and repeat-dose studies in monkeys, dose-limited acute tubular necrosis of the kidneys was the chief finding. In reproductive studies, drug-related changes were decreased food intakes, decreased testis weight and uterus weight, decreased foetus weight and increased foetus mortality, increased maternal and F1 offspring mortality and decreased maternal and F1 offspring body weight. Pharmacokinetic studies showed a similar half-time of distribution and clearance in mice and monkeys. Tissue distribution showed a high concentration in the kidneys and a low concentration in the brain. LHRH-PE40 induced vascular leak syndromes in rats and acute tubular necrosis in monkeys. It also led to testicle atrophy in rats and overt productive toxicity to parents and F1 generations in mice. Because of these findings, it should be monitored carefully in human clinical trials for things such as respiratory, urinary and reproductive toxicities.

ADP Ribose Transferases↗

PubMed2006

Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab' fragment.

AIM: To perform a site-specific conjugation of Fab' fragments of a mouse monoclonal antibody(MoAb) B43(of IgG1 subtype) to a bifunctional chelator 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N' 'N' ' '-tetraacetic acid (BAT) via the thiol groups in the hinge distal to the antigen-binding site of the Fab'. METHODS: B43 was cleaved using a simple 2-step method. First, stable F(ab')(2) was produced by pepsin treatment. Fab' with free thiol in the hinge region was then obtained by cysteine reduction of F(ab')2. Second, a site-specific conjugation of Fab' to thiol-specific BAT was performed in a one-step reaction. RESULTS: The Fab' fragment had approximately 1.8 free thiol groups per molecule after cysteine reduction. The conjugation efficiency and the chemical yield were approximately 1.28 moles chelator/Fab' and 74% of the initial concentration of Fab', respectively. The F(ab')2, Fab' and Fab'-BAT all maintained reasonable antigen-binding properties. (67)Cu labeling of the conjugate under standard conditions did not impair the immunoreactivity of Fab'-BAT. CONCLUSION: This is a simple and efficient method for producing immunoreactive conjugates of Fab'-BAT, which can be used to make radiometal-labeled conjugates for further diagnostic and therapeutic applications.

Acetamides↗

PubMed2006

Changes with age and the effect of recombinant human BMP-2 on proteoglycan and collagen gene expression in rabbit anulus fibrosus cells.

In order to compare the difference between young and old intervertebral disc cells and their responsiveness to recombinant human bone morphogenetic protein-2 (rhBMP-2), disc cells were isolated from the anulus fibrosus (AF) and transition zones of lumbar discs from eight old and eight young New Zealand white rabbits. Compared with the cells from the young rabbits, cells from old rabbits respond less to rhBMP-2 treatment with respect to sulfated-glycosaminoglycan (sGAG) synthesis and aggrecan gene expression. But in collagen I and collagen II gene expressions, there are no significant differences between the old and the young. When comparing sGAG content, aggrecan, and collagen II gene expression of the old AF cells after rhBMP-2 treatment with that of the young AF cells without rhBMP-2 treatment, the old AF cells with rhBMP-2 treatment have a greater capacity to synthesize sGAG bound in the cells and to release sGAG in the media, as well as to express aggrecan and collagen II gene. It can be concluded that old AF cells after rhBMP-2 treatment have a greater capacity to synthesize sGAG and express aggrecan and collagen II as compared to young AF cells without rhBMP-2 treatment. Thus rhBMP-2 can reverse the decline in the anabolic capacity of the disc cells with ageing. So it seems that rhBMP-2 has potential for use as an agent to retard a key component of disc degeneration and loss of disc matrix.

Aggrecans↗

PubMed2006

A computed tomography implementation of multiple-image radiography.

Conventional x-ray computed tomography (CT) produces a single volumetric image that represents the spatially variant linear x-ray attenuation coefficient of an object. However, in many situations, differences in the x-ray attenuation properties of soft tissues are very small and difficult to measure in conventional x-ray imaging. In this work, we investigate an analyzer-based imaging method, called computed tomography multiple-image radiography (CT-MIR), which is a tomographic implementation of the recently proposed multiple-image radiography method. The CT-MIR method reconstructs concurrently three physical properties of the object. In addition to x-ray attenuation, CT-MIR produces volumetric images that represent the refraction and ultrasmall-angle scattering properties of the object. These three images can provide a rich description of the object's physical properties that are revealed by the probing x-ray beam. An imaging model for CT-MIR that is based on the x-ray transform of the object properties is established. The CT-MIR method is demonstrated by use of experimental data acquired at a synchroton radiation imaging beamline, and is compared to the pre-existing diffraction-enhanced imaging CT method. We also investigate the merit of an iterative reconstruction method for use with future clinical implementations of CT-MIR, which we anticipate would be photon limited.

Humans↗

PubMed2006

Immunomodulating effects of fractioned polysaccharides isolated from Yu-Ping-Feng-Powder in cyclophosphamide-treated mice.

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-gamma production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

Administration, Oral↗

PubMed2006

Potent activation of mitochondria-mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract.

We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal isothiocyanate present in broccoli sprout extracts, sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In this article, we show that an aqueous extract of broccoli sprouts potently inhibits the growth of human bladder carcinoma cells in culture and that this inhibition is almost exclusively due to the isothiocyanates. Isothiocyanates are present in broccoli sprouts as their glucosinolate precursors and blocking their conversion to isothiocyanates abolishes the antiproliferative activity of the extract. Moreover, the potency of isothiocyanates in the extract in inhibiting cancer cell growth was almost identical to that of synthetic sulforaphane, as judged by their IC50 values (6.6 versus 6.8 micromol/L), suggesting that other isothiocyanates in the extract may be biologically similar to sulforaphane and that nonisothiocyanate substances in the extract may not interfere with the antiproliferative activity of the isothiocyanates. Further study showed that the isothiocyanate extract of broccoli sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with down-regulation of Cdc25C and disruption of mitotic spindles. These data show that broccoli sprout isothiocyanate extract is a highly promising substance for cancer prevention/treatment and that its antiproliferative activity is exclusively derived from isothiocyanates.

Apoptosis↗

PubMed2006

Self-association and micelle formation of biodegradable poly(ethylene glycol)-poly(L-lactic acid) amphiphilic di-block co-polymers.

Di-block co-polymers of poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLLA) were prepared by ring-opening polymerization, and their self-association and micelle formation were investigated. The block co-polymers have the same block length of the hydrophilic PEG segment (Mn = 2000), but different chain lengths of the hydrophobic PLLA segment (Mn = 700, 1000 and 1300, respectively). The di-block co-polymers synthesized were characterized by GPC, 1H-NMR, TGA and DSC. The critical micelle concentration (CMC) of the PEG-PLLA micelles was determined at various temperatures (5-45 degrees C) using a dye absorption technique involving fluorescence spectrophotometry with pyrene as a probe to monitor the change in the polarity of the microenvironment in the micelle. An increase in the molecular weight of the hydrophobic block decreases the CMC. The partition coefficients of pyrene between the micellar and aqueous phases range from 0.68 x 10(4 )to 1.76 x 10(4), depending on the PLLA content in the block co-polymers. An Arrhenius plot of ln(CMC) versus 1/T exhibited an almost constant CMC at low temperatures (<35 degrees C), followed by an increase of the CMC at higher temperatures (>35 degrees C). The increase of the CMC with temperature indicates the increase of the mobility of the hydrophobic PLLA core. These results were confirmed by 1H-NMR measurements. The micelle size and size distribution were determined by dynamic light scattering (DLS), and were in the range of 78-92 nm. A spherical micelle shape was confirmed by transmission electron microscopy. These results indicate that the CMC and the thermal characteristics of the core-forming segment of the block co-polymer play an important role in the properties of the polymer micelles used for drug delivery.

Biodegradation, Environmental↗

PubMed2006

Synthesis and characterization of sub-10 nm Platinum Hollow Spheres as electrocatalyst of direct methanol fuel cell.

Platinum Hollow Spheres (PHSs) with diameters less than 10 nm were successfully synthesized by using Co as a sacrificial template and H2PtCl6 as an oxidizing agent at 95 degrees C. The formation of PHSs at this temperature was not affected by citrate reduction and mainly depended on the pH. The results of transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis demonstrated that the platinum hollow sphere was mainly constructed by fcc (face cubic center) platinum with tiny crystallites on the shell. The performance of PHSs for methanol electro-oxidation was evaluated and compared with commercial E-TEK platinum black. Electrochemical measurement by cyclic voltammetry (CV) demonstrated that the electrochemical surface area of PHSs was about twice higher than E-TEK platinum black. Therefore, the synthesized PHSs had higher electrocatalytic activity for methanol electro-oxidation.

Catalysis↗

PubMed2006

Evaluation of isothiocyanates as potent inducers of carcinogen-detoxifying enzymes in the urinary bladder: critical nature of in vivo bioassay.

Deficiency of carcinogen-detoxifying phase 2 enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increases bladder cancer risk in humans. We report that several isothiocyanates (ITCs) that have not been previously examined, 1-methylbutyl ITC in particular, potently and preferentially induce both GST and NQO1 in the rat bladder. Comparison of 25 ITCs that are closely related in chemical structures showed that a 3-5-carbon aliphatic side chain with a methyl group attached to the alpha carbon was crucial for maximal inducer activity in the bladder. Surprisingly, cell-based bioassays failed to predict the phase 2 enzyme-inducing activity of the ITCs in the bladder. Furthermore, although ITCs are principally metabolized in vivo to dithiocarbamates (DTCs), which are believed to serve as the carriers of ITCs and are rapidly eliminated and concentrated in the urine, the total urinary levels of ITC plus DTC did not correlate with the degree of GST and NQO1 induction by the ITCs in the bladder of rats. Thus, several underappreciated ITCs are exceedingly potent inducers of GST and NQO1 in the rat bladder but were predicted neither by in vitro bioassays of phase 2 enzyme induction nor by their appearance or concentration in urine in vivo.

Animals↗

PubMed2006

Correlation between plasma glucagon-like peptide 2 levels and proliferative makers in small intestinal injury in rats induced by methotrexate administration.

Glucagon-like peptide 2 (GLP-2) is a potent intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We examined whether a relationship exists between plasma level of GLP-2 and the degree of intestinal injury induced by chemotherapeutic agents in the rat. Methotrexate (MTX) was administrated orally for 6 consecutive days at doses of 1.25, 2.5, and 5.0 mg/kg body weight per day. Mucosal samples of rat duodenum, jejunum, and ileum were used for assessment of mucosal weight, DNA and protein content. Plasma GLP-2 levels were measured on day 8. MTX significantly reduced body weight. The values of all indices tended to decrease in all segments with increases in MTX dose. Plasma GLP-2 levels were significantly higher in the MTX 2.5 mg/kg/d group (p<0.05) and the MTX 5.0 mg/kg/d group (p<0.01) than in the control group. Correlations were found between plasma GLP-2 levels and mucosal weight, DNA and protein content. We concluded that plasma GLP-2 levels reflect the degree of intestinal injury following MTX administration in this preclinical model.

Administration, Oral↗

PubMed2006

Rhodiolosides A-E, monoterpene glycosides from Rhodiola rosea.

Five new monoterpene glycosides, rhodiolosides A-E (1-5), were isolated from the roots of Rhodiola rosea (Crassulaceae). Their structures were elucidated as (2E,6E,4R)-4,8-dihydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranoside (1), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl alpha-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (2), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranoside (3), (2E,4R)-4,7-dihydroxy-3,7-dimethyl-2-octenyl beta-D-glucopyranoside (4), and (2E)-7-hydroxy-3,7-dimethyl-2-octenyl alpha-L-arabinopyranosyl(1-->6)-beta-D-glucopyranoside (5), on the basis of various spectroscopic analyses and chemical degradation.

Carbohydrate Sequence↗

PubMed2006

Steroidal glycosides and aromatic compounds from Smilax riparia.

Two new steroidal glycosides named riparosides A (1) and B (2), and two aromatic compounds (3, 4), together with four known flavonoid derivatives have been isolated from the EtOH extract of the rhizomes and roots of Smilax riparia A. DC. The structure of riparoside A (1) was determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl 3beta,20alpha-dihydroxy-5alpha-furost-22(23)-ene 26-O-beta-D-glucopyranoside. Riparoside B (2) was characterized as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl 3beta,16beta-dihydroxy-5alpha-pregnan-20-one 16-O-[5-O-beta-D-glucopyranosyl 5-hydroxy-4-methyl-pentanoic acid]-ester 26-O-beta-D-glucopyranoside. Compounds 3 and 4 were elucidated as a sucrosyl ferulic acid ester and 7-O-methyl-10-oxythymol gentiobioside, respectively.

Glycosides↗

PubMed2006

Jaspolides A-F, six new isomalabricane-type terpenoids from the sponge Jaspis sp.

A chemical investigation of Jaspis sp., the marine sponge collected from the South China Sea led to the isolation of six new isomalabaricane-type compounds, jaspolides A-F (1-6). The structures of those compounds were elucidated by extensive spectroscopic methods. The structure-types of 1 to 6 could be classified into triterpenes (1, 2), sesterterpene (6), diterpenes (3, 4), and nortriterpene (5). The biogenetic transformation of the isolated compounds was also speculated.

Animals↗

PubMed2006

SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection.

Skp1-cullin-F-box protein (SCF) is a multicomponent E3 ubiquitin (Ub) ligase that ubiquitinates a number of important biologic molecules such as p27, beta-catenin, and IkappaB for proteasomal degradation, thus regulating cell proliferation and survival. One SCF component, SAG/ROC2/Rbx2/Hrt2, a RING finger protein, was first identified as a redox-inducible protein, which, when overexpressed, inhibited apoptosis both in vitro and in vivo. We report here that sensitive to apoptosis gene (SAG), as well as its family member ROC1/Rbx1, bound to the proinactive form of caspase-3 (pro-caspase-3). Binding was likely mediated through F-box protein, beta-transducin repeat-containing protein (beta-TrCP), which binds to the first 38 amino acids of pro-caspase-3. Importantly, beta-TrCP1 expression significantly shortened the protein half-life of pro-caspase-3, whereas expression of a dominant-negative beta-TrCP1 mutant with the F-box domain deleted extended it. An in vitro ubiquitination assay showed that SAG/ROC-SCF(beta-TrCP) promoted ubiquitination of pro-caspase-3. Furthermore, endogenous levels of pro-caspase-3 were decreased by overexpression of SAG/ROC-SCF(beta-TrCP) E3 Ub ligases, but increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1), or beta-TrCPs, leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing ligand through increased activation of caspase-3. Thus, pro-caspase-3 appears to be a substrate of SAG/ROC-SCF(beta-TrCP) E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3.

Apoptosis↗

PubMed2006

[Effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice].

OBJECTIVE: To evaluate the effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice. METHODS: One hundred and five nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were randomly divided into seven groups: untreated group, normal saline-treated group, dissolvant-treated group, cyclophosphamide (CTX)-treated group and high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups. Corresponding interventions were implemented in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM). The ultrastructure of MKN-45 gastric cancer cells was observed by a transmission electron microscope. RESULTS: In the high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups, the growth inhibition rates of gastric cancer were 57.2%, 28.0% and 5.0% respectively, and the gastric cancer cells were arrested at G(0)/G(1) phase. This antitumor effect was dose-dependent. The apoptotic cells occurred more frequently in the high-dose Rhizoma kaempferiae volatile oil-treated group and the CTX-treated group than those in the medium- and low-dose Rhizoma kaempferiae volatile oil-treated groups. CONCLUSION: The Rhizoma kaempferiae volatile oil is an effective composition for growth inhibition of gastric cancer, and its mechanism may be related to regulating the cell cycle and inducing apoptosis.

Animals↗