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Biomedical subjects

Jia Li

Publications and source records attributed to Jia Li.

At least 37 records · Page 2Linked to original sources
PubMed2006

Separation and identification of major plant sphingolipid classes from leaves.

Sphingolipids are major components of the plasma membrane, tonoplast, and other endomembranes of plant cells. Previous compositional analyses have focused only on individual sphingolipid classes because of the widely differing polarities of plant sphingolipids. Consequently, the total content of sphingolipid classes in plants has yet to be quantified. In addition, the major polar sphingolipid class in the model plant Arabidopsis thaliana has not been previously determined. In this report, we describe the separation and quantification of sphingolipid classes from A. thaliana leaves using hydrolysis of sphingolipids and high performance liquid chromatography (HPLC) analysis of o-phthaldialdehyde derivatives of the released long-chain bases to monitor the separation steps. An extraction solvent that contained substantial proportions of water was used to solubilized >95% of the sphingolipids from leaves. Neutral and charged sphingolipids were then partitioned by anion exchange solid phase extraction. HPLC analysis of the charged lipid fraction from A. thaliana revealed only one major anionic sphingolipid class, which was identified by mass spectrometry as hexose-hexuronic-inositolphosphoceramide. The neutral sphingolipids were predominantly composed of monohexosylceramide with lesser amounts of ceramides. Extraction and separation of sphingolipids from soybean and tomato showed that, like A. thaliana, the neutral sphingolipids consisted of ceramide and monohexosylceramides; however, the major polar sphingolipid was found to be N-acetyl-hexosamine-hexuronic-inositolphosphoceramide. In extracts from A. thaliana leaves, hexosehexuronic-inositolphosphoceramides, monohexosylceramides, and ceramides accounted for approximately 64, 34, and 2% of the total sphingolipids, respectively, suggesting an important role for the anionic sphingolipids in plant membranes.

Anions↗
PubMed2006

Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake.

Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

Animals↗
PubMed2006

Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans.

OBJECTIVES: We conducted a randomized controlled trial of the effects of remote ischemic preconditioning (RIPC) in children undergoing repair of congenital heart defects. BACKGROUND: Remote ischemic preconditioning reduces injury caused by ischemia-reperfusion in distant organs. Cardiopulmonary bypass (CPB) is associated with multi-system injury. We hypothesized that RIPC would modulate injury induced by CPB. METHODS: Children undergoing repair of congenital heart defects were randomized to RIPC or control treatment. Remote ischemic preconditioning was induced by four 5-min cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Measurements of lung mechanics, cytokines, and troponin I were made pre- and postoperatively. RESULTS: Thirty-seven patients were studied. There were 20 control patients and 17 patients in the RIPC group. The mean age and weight of the RIPC and control patients were not different (0.9 +/- 0.9 years vs. 2.2 +/- 3.4 years, p = 0.4; and 6.9 +/- 2.9 kg vs. 11.5 +/- 10 kg, p = 0.06). Bypass and cross-clamp times were not different (80 +/- 24 min vs. 88 +/- 25 min, p = 0.3; and 55 +/- 13 min vs. 59 +/- 13 min, p = 0.4). Levels of troponin I postoperatively were greater in the control patients compared with the RIPC group (p = 0.04), indicating greater myocardial injury in control patients. Postoperative inotropic requirement was greater in the control patients compared with RIPC patients at both 3 and 6 h (7.9 +/- 4.7 vs. 10.9 +/- 3.2, p = 0.04; and 7.3 +/- 4.9 vs. 10.8 +/- 3.9, p = 0.03, respectively). The RIPC group had significantly lower airway resistance at 6 h postoperatively (p = 0.009). CONCLUSIONS: This study demonstrates the myocardial protective effects of RIPC using a simple noninvasive technique of four 5-min cycles of lower limb ischemia and reperfusion. These novel data support the need for a larger study of RIPC in patients undergoing cardiac surgery.

Child, Preschool↗
PubMed2006

Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status.

BACKGROUND AND PURPOSE: Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States. METHODS: The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.4 years of follow-up were compared with 560 controls. RESULTS: Marginal associations with stroke (P<0.10) were found for 3 polymorphisms. Stratification of the population by hypertension markedly strengthened the association. SNPs 9 (hazard ratio [HR], 0.48; 95% CI, 0.26 to 0.91), 42 (HR, 1.73; 95% CI, 1.10 to 2.70), 219 (HR, 1.73; 95% CI, 1.13 to 2.64), and 220 (HR, 1.56; 95% CI, 1.05 to 2.32) showed significant association with stroke (P<0.05) under a dominant model in subjects without hypertension at baseline, and SNP 175 was significantly associated with stroke under an additive model (HR, 0.76; 95% CI, 0.59 to 0.98) in subjects with hypertension. Furthermore, the microsatellite AC008818-1 showed association with stroke only in the nonhypertensive subjects. Based on results in Iceland, specific haplotypes were tested in SOF, and stratification by hypertension also affected these association results. CONCLUSIONS: These data are consistent with an association of the PDE4D gene with stroke in a non-Icelandic sample and suggest an effect of hypertension status.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Comparative study on the interaction of DNA with three different kinds of surfactants and the formation of multilayer films.

The interactions between double-stranded DNA (dsDNA) and three different kinds of surfactants, i.e., cationic, anionic, and nonionic surfactants, were investigated by cyclic voltammetry, electrochemical impedance spectroscopy and UV-vis spectroscopy. Multilayer films composed of DNA and surfactants were prepared at gold electrode by electrostatic or hydrophobic interactions. It was found that the cationic surfactant, CTAB, can bind to DNA by electrostatic interaction, and the electron transfer resistance of CTAB-DNA complex film increases first and then decreases with CTAB concentration. The anionic surfactant, LAS, can bind to DNA but by hydrophobic interaction, and the electron transfer resistance of the complex film keeps decreasing with LAS concentration. Nonionic surfactants can also directly bind to DNA by hydrophobic interaction. All the three different kinds of surfactants can form multilayer films with DNA on the electrode surface. The chemical structure of DNA keeps unchanged during interacting with these surfactants. The binding modes of DNA with these three different kinds of surfactants were also deduced.

Binding Sites↗
PubMed2006

Design and synthesis of a biotin-tagged photoaffinity probe of paeoniflorin.

A trifunctional probe (binding element-photoreactive group-affinity tag) of natural product paeoniflorin was designed and synthesized based on the previous primary structure-activity relationship. This new probe is a potential tool for labeling, purification, and identification of the target proteins.

Animals↗
PubMed2006

Inclusion of oxygen consumption improves the accuracy of arterial and venous oxygen saturation interpretation after the Norwood procedure.

OBJECTIVE: Management strategy for the postoperative Norwood neonate has been formulated from models that have estimated oxygen consumption (VO2). Superior vena caval oxygen saturation (SVO2), systemic arterial and superior vena caval oxygen saturation difference (Sa-VO2), and oxygen excess factor (Omega = arterial oxygen saturation/Sa-VO2) have been used as indirect indicators to estimate systemic blood flow (Qs) and oxygen delivery (DO2). We sought to examine the correlation of the indirect indicators to VO2-derived measures of oxygen transport. METHODS: Respiratory mass spectrometry was used to continuously measure VO2 after the Norwood procedure (n = 13). Measured saturations and the direct Fick equation were used to obtain pulmonary blood flow, Qs, DO2, and oxygen extraction ratio (ERO2) values. Correlations to SVO2, Sa-VO2, and Omega were sought. RESULTS: There was a close correlation of SVO2, Sa-VO2, and Omega to ERO2 (r = 0.92, 0.96, and 0.97, respectively; P < .0001). Correlation to Qs and DO2 was variable (r = 0.39 to 0.78, respectively; P < .0001). Correlation to VO2 was poor but significant (r = 0.24 to 0.40, P < .0001). Inclusion of VO2 improved the correlation to Qs and DO2 (r = 0.66 to 0.97, P < .0001). CONCLUSIONS: The close correlation of SVO2, Sa-VO2, and Omega to ERO2 indicates that each is a measure of the balance of DO2 and extraction. The significant but less reliable correlation to DO2 and VO2 indicates the values for SVO2, Sa-VO2, and Omega do not discriminate between the contribution of DO2 and VO2. Measured VO2 and hemodynamics may improve the optimization of postoperative management strategy in the individual neonate.

Cardiac Surgical Procedures↗
PubMed2006

Design, synthesis, and biological evaluation of isoquinoline-1,3,4-trione derivatives as potent caspase-3 inhibitors.

A series of isoquinoline-1,3,4-trione derivatives were identified as novel and potent inhibitors of caspase-3 through structural modification of the original compound from high-throughput screening. Various analogues (2, 6, 9, 13, and 14) were synthesized and identified as caspase inhibitors, and the introduction of a 6-N-acyl group (compound 13) greatly improved their activity. Some of them showed low nanomolar potency against caspase-3 in vitro (for example, for 6k, IC50 = 40 nM) and significant protection against apoptosis in a model cell system. Additionally, compound 13f demonstrated a dose-dependent decrease in infarct volume in the transient MCA occlusion stroke model. The present small-molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis.

Animals↗
PubMed2006

Design, synthesis, and evaluation of Leu*Ala hydroxyethylene-based non-peptide beta-secretase (BACE) inhibitors.

With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600).

Amyloid Precursor Protein Secretases↗
PubMed2006

Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: the SOF study.

Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was measured at an initial exam and after an average of 5.9 years of follow-up. Hip BMD was measured at an initial exam and after 3.7 years of follow-up. Baseline spine BMD and hip structural parameters were measured. Incident hip fractures were confirmed by review of radiographic reports; follow-up was greater than 98% complete. Incident vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. The frequencies of the NOS3 Glu298Asp genotypes were Glu/Glu=46.2%, Glu/Asp=42.7%, and Asp/Asp=11.1%. There were no significant associations between NOS3 genotypes and initial calcaneal BMD, hip BMD, or rate of change in hip or calcaneal BMD. None of the hip structural parameters differed substantially by genotype. NOS3 genotype was not significantly associated with either incident or prevalent radiographic vertebral fractures. Women with the heterozygous Glu/Asp genotype had a borderline statistically significantly lower rate of hip fracture than either the Glu/Glu genotype (HR=0.87, 95% CI: 0.74, 1.01) or the Asp/Asp genotype (HR=0.78, 95% CI: 0.62, 0.98). In conclusion, the Glu298Asp polymorphism does not contribute substantially or consistently to indices of bone strength in this sample of older white women, although our findings suggest allelic variation at the NOS3 locus maybe associated with hip fracture risk. Confirmation of these findings is needed in other populations and with additional markers within and flanking the NOS3 gene region.

Age Factors↗
PubMed2006

Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids.

The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows protection against PPE-induced emphysema.

Animals↗
PubMed2006

Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.

Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumor cell lines A549 and HCT-116, producing IC(50) values in the micromolar range.

Cell Line, Tumor↗
PubMed2006

Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L.

Three new withanolide glycosides named daturametelins H-J (1-3), together with two known ones, daturataturin A (4) and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide (5), were isolated from the MeOH extract of the aerial parts of Datura metel L. (Solanaceae). Their structures were determined mainly by spectroscopic techniques including 2D-NMR (HMBC, HMQC, (1)H,(1)H-COSY, NOESY) and MS experiments. Compounds 1-5 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line. The nonglycosidic compound 5 exhibited the highest activity of the tested withanolides, with an IC(50) value of 3.2+/-0.2 microM (Table 3).

Antineoplastic Agents, Phytogenic↗
PubMed2006

Conditional deletion of the colony stimulating factor-1 receptor (c-fms proto-oncogene) in mice.

Colony stimulating factor-1 (CSF-1) is the primary regulator of the mononuclear phagocytic lineage acting through its transmembrane tyrosine kinase receptor, CSF-1R, that is the product of the c-fms proto-oncogene. Null mutations in either the ligand or the receptor genes result in a severe osteopetrosis as well as a number of other phenotypes, including reproductive defects and perturbations in organ development. The CSF-1R is also expressed in oocytes, myoblast progenitors, decidual, and trophoblastic cells. To distinguish cell type specific phenotypes, we have created a conditional allele of the Csf1r by placing LoxP sites around Exon 5 of the Csf1r gene in mice. Excision of this floxed sequence results in a null allele that in the homozygous state gives a phenotype indistinguishable of the complete Csf1r null mutant mouse. This conditional allele will prove extremely valuable to study the spatial and temporal roles of CSF-1R.

Animals↗
PubMed2006

Doppler tissue imaging in the assessment of atrioventricular conduction time: validation of a novel technique and comparison with electrophysiologic and pulsed wave Doppler-derived equivalents in an animal model.

Accurate assessment of atrioventricular conduction time (AVCT) is crucial for early detection of evolving fetal heart block. Simultaneous pulsed wave Doppler (PD) interrogation of left ventricular inflow and outflow is mainly used to study fetal AVCT. Limitations of this modality include its dependency on loading conditions and merging early and late diastolic inflow waves at faster heart rate (HR). Sequential analysis of atrioventricular myocardial motion by Doppler tissue imaging (DTI) might be more useful in this regard. In 15 open-chest pigs, AVCT was measured by PD, DTI, and electrocardiogram at baseline HR and during incremental atrial pacing up to 200 beats/min. Electromechanical delay and pre-ejection period were assessed at baseline and maximal HR. DTI-derived AVCT correlated better with PR intervals and allowed measurements at faster HRs than did PD (P < .05). Pre-ejection period prolonged with faster HR (P < .001), unlike electromechanical delay. In conclusion, DTI allows more accurate measurement of AVCT over a wider HR range than does PD.

Animals↗
PubMed2006

Characterization of frequently deleted 6q locus in prostate cancer.

The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of 6qTSG transcripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted.

Apoptosis↗