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Biomedical subjects

Jun Li

Publications and source records attributed to Jun Li.

At least 37 records · Page 2Linked to original sources
PubMed2007

Theoretical studies on the excited states, DNA photocleavage, and spectral properties of complex [Ru(phen)(2)(6-OH-dppz)](2+).

The structures and related properties of the complex [Ru(phen)2(6-OH-dppz)]2+ (phen = 1,10-phenanthroline; dppz = dipyrido [3,2-a:2',3'-c]phenazine) in the ground state (S0), the first singlet excited state (S1), and the first triplet excited state (T1) have been studied using density functional theory (DFT), time-dependent (TD) DFT, Hartree-Fock (HF), and configuration interaction singles (CIS) methods. Three electronic absorption-spectral bands (1MLCT, 1LL, and 1LL) lying in the range of 250-550 nm in vacuo and in aqueous solution were theoretically calculated, simulated, and assigned with TDDFT method. In particular, the theoretical results show the following: (1) The positive charges of central Ru atom in the excited states (S1 and T1) are greatly increased relative to those in the ground state (S0), and thus the Ru atom in the excited states can be regarded as Ru(III). (2) The positive charges on the main ligand (6-OH-dppz) in the excited states are considerably reduced, and thus the interaction between the main ligand (intercalative ligand) and DNA base pairs is considerably weakened. (3) The geometric structures in excited states are also distorted, resulting in obvious increase in the coordination bond length. It is advantageous to the complex forming a high oxidizing center (i.e., Ru(III) ion). On the basis of these results, a theoretical explanation on photoinduced oxidation reduction mechanism of DNA photocleavage by [Ru(phen)2(6-OH-dppz)](2+) has been presented.

DNA↗
PubMed2007

Directed reductive amination of beta-hydroxy-ketones: convergent assembly of the ritonavir/lopinavir core.

An efficient procedure for the directed reductive amination of beta-hydroxy-ketones (3) for the stereoselective preparation of 1,3-syn-amino alcohols (6) is reported. The operationally simple protocol uses Ti(iOPr)4 for coordination of the intermediate imino alcohol (5) and PMHS as the reducing agent. The method was expanded to an asymmetric aldol reductive amination sequence to allow a highly convergent synthesis of the hydroxy-amine core of the HIV-protease inhibitors ritonavir and lopinavir. [reaction: see text].

Amination↗
PubMed2007

Histone acetyltransferase p300 modulates gene expression in an epigenetic manner at high blood alcohol levels.

When rats are fed ethanol intragastrically at a constant rate for 1 month, the urinary alcohol level (UAL) cycles over 7-9 day intervals. At the peak UAL, the liver is hypoxic shifting the redox state to a reduced rate. Microarray analysis done on livers at the UAL peaks shows changes in approximately 1300 gene expression compared to the pair-fed controls. To determine the mechanism of the gene expression changes, histone acetylation regulation was investigated in liver nuclear extracts at the peaks and troughs of the UAL and their pair-fed controls. No change occurred in SirT-1. P300, a histone acetyltransferase (HAT), which acetylates histone H3 on lysine 9, was increased at the peaks. Histone 3 acetylated at lysine 9 was also increased at the peaks. This indicates that the up regulated genes at the UAL peaks resulted from an increase in p300 transcription regulation, epigenetically. P300 activates transcription of numerous genes in response to signal transcription factors such as H1F 1alpha, increased in the nucleus at UAL peaks. Signal transduction pathways, such as NFkappaB, AP-1, ERK, JNK, and p38 were not increased at the peaks. beta-Catenin was increased in the nuclear extract at the UAL troughs, where increased gene expression was absent. The increase in gene expression at the peaks was due, in part, to increased acetylation of histone 3 at lysine 9.

Acetylation↗
PubMed2007

Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Prior work has shown reduced serotonin transmission to be associated with impulsivity and behavioral problems. The current study assessed the association between ADHD and two variants of the serotonin transporter gene: the 44-bp deletion/insertion polymorphism (5-HTTLPR) and the 17 bp-repeat polymorphism in intron 2 (STin2.VNTR). We hypothesized that ADHD phenotypes associated with impulsivity would show an association with these variants. Two-hundred and ninety-three ADHD trios were genotyped and analyzed using transmission disequilibrium test (TDT) analysis and haplotype analysis. We found no association between the STin2.VNTR and ADHD, but did find preferential transmission of the S allele of the 5-HTTLPR polymorphism (chi(2) = 5.751, P = 0.016) to probands with ADHD. Haplotype analysis found the L/10 haplotype was over-transmitted (chi(2) = 6.172, P = 0.013), while L/12 was under-transmitted to probands with ADHD (chi(2) = 4.866, P = 0.027).

Alleles↗
PubMed2007

MTO Schiff-base complexes: synthesis, structures and catalytic applications in olefin epoxidation.

Several Schiff-base ligands readily form complexes with methyltrioxorhenium(VII) (MTO) by undergoing a hydrogen transfer from a ligand-bound OH group to a ligand N atom. The resulting complexes are stable at room temperature and can be handled and stored in air without problems. Due to the steric demands of the ligands they display distorted trigonal-bipyramidal structures in the solid state, as shown by X-ray crystallography, with the O(-) moiety binding to the Lewis acidic Re atom and the Re-bound methyl group being located either in cis or trans position to the Schiff base. In solution, however, the steric differences seem not to be maintained, as can be deduced from (17)O NMR spectroscopy. Furthermore, the Schiff-base ligands exchange with donor ligands. Nevertheless, the catalytic behaviour is influenced significantly by the Schiff bases coordinated to the MTO moiety, which lead either to high selectivities and good activities or to catalyst decomposition. A large excess of ligand, in contrast to the observations with aromatic N-donor ligands, is detrimental to the catalytic performance as it leads to catalyst decomposition.

Journal Article↗
PubMed2007

Hydrogel-filled polylactide porous scaffolds for cartilage tissue engineering.

Polymer porous scaffolds and hydrogels have been separately employed as analogues of the native extra-cellular matrix (ECM). However, both of these two kinds of materials have their own advantages and shortcomings. In this work, an attempt to combine the advantages of these two kinds of materials is carried out. Poly-L-lactide (PLLA) scaffolds with good mechanical properties were prepared by thermally induced phase separation, which were then filled with hydrogel aiming at entrapment of cells within a support of predefined shape. Agar, which has a function to promote chondrogenesis, was selected to entrap chondrocytes, acting as analogues of native ECM. A straight forward merit of this construct is that both mechanical strength and macroscopic shape, and analogous ECM can be simultaneously achieved. The morphology and distribution of the chondrocytes were studied by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The cell growth behaviors were determined by MTT assay and collagen and glycosaminoglycan (GAG) secretion. After culture for 7 and 14 days, the cells in the construct were round and surrounded by the hydrogel. The MTT viability and the cell secretion in the chondrocytes/agar/scaffold construct were also higher than that of the chondrocytes/scaffold construct (control). Gelatin was further introduced into the construct, yielding improved GAG secretion and cytoviability. After implantation in the subcutaneous dorsum of nude mice for 4 weeks, cartilage-like specimens maintaining their original rectangular shapes were harvested. Histological examination showed that new cartilage was regenerated and a large quantity of collagen and GAG were secreted, while the cells in the control PLLA scaffold turned to be fibroblast-like with less secretion of extracellular matrices. The method provides a useful pathway of scaffold preparation and cell transplantation, which can achieve suitable mechanical properties and good cell performance simultaneously.

Animals↗
PubMed2007

Finite element analysis of impact loads on the femur.

OBJECTIVE: To investigate the stress distribution and fracture mechanism of proximal femur under impact loads. METHODS: The image data of one male's femur were collected by the Lightspeed multi-lay spiral computed tomography. A 3D finite element model of the femur was established by employing the finite element software ANSYS, which mainly concentrated on the effects of the directions of the impact loads arising from intense movements and the parenchyma on the hip joint as well as those of the femur material properties on the distribution of the Mises equivalent stress in the femur after impact. RESULTS: The numerical results about the effects of the angle sigma of the impact loads to the anterior direction and the angle gamma of the impact loads to the femur shaft on the bone fracture were given. The angle sigma had larger effect on the stress distribution than the angle gamma, which mainly represented the fracture of the upper femur including the femoral neck fracture when the posterolateral femur was impacted. This result was consistent with the clinical one. The parenchyma on the hip joint has relatively large relaxation effect on the impact loads. CONCLUSIONS: A 3D finite element analysis model of the femoral hip joint under dynamic loads is successfully established by using the impact dynamic theory.

Femur↗
PubMed2006

A simplified method for estimation of jarosite and acid-forming sulfates in acid mine wastes.

In acid base accounting (ABA) estimates of acid mine wastes, the acid potential (AP) estimate can be improved by using the net carbonate value (NCV) reactive sulfide S method rather than total S assay methods but this does not give recovery of potentially acid producing ferrous and ferric sulfates present in many wastes. For more accurate estimation of AP, an effective, site-specific method to quantify acid sulfate salts, such as jarosite and melanterite, in waste rocks has been developed and tested on synthetic and real wastes. The SPOCAS (acid sulfate soils) methods have been modified to an effective, rapid method to speciate sulfate forms in different synthetic waste samples. A three-step sequential extraction procedure has been established. These steps are: (1) argon-purged water extraction (3 min) to extract soluble Fe(II) salts (particularly melanterite), epsomite and gypsum (<10 wt.%), (2) roasting at 550 degrees C (1 h) to remove sulfur from pyrite and other reactive sulfides, (3) HCl extraction (4 M, 30 min) for determination of jarosites. Products (solid and aqueous) have been characterized at each step including the jarosite decomposition process in Step 2 where temperature control is critical to avoid S loss. The sequential extraction procedure was used to quantitatively determine melanterite, epsomite, gypsum, pyrite and jarosite concentrations in a synthetic waste sample containing these mineral phases at 5 wt.% in quartz, and also tested using a tailings waste sample to quantitatively determine epsomite, gypsum and jarosite contents. The method is applicable to most waste samples including those with non-pyrite sulfides but for samples containing significant amounts of sulfur (>1 wt.% S) as copper sulfides, the second step of roasting needs to be excluded from the procedure with an increased time of 4 M HCl extraction to 16 h for jarosite determination.

Journal Article↗
PubMed2006

Preliminary crystallographic analysis of avian infectious bronchitis virus main protease.

Infectious bronchitis virus (IBV) is the prototype of the genus Coronavirus. It causes a highly contagious disease which affects the respiratory, reproductive, neurological and renal systems of chickens, resulting great economic losses in the poultry industry worldwide. The coronavirus (CoV) main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, is an attractive target for antiviral drug design. In this study, IBV M(pro) was overexpressed in Escherichia coli. Crystals suitable for X-ray crystallography have been obtained using microseeding techniques and belong to space group P6(1)22. X-ray diffraction data were collected in-house to 2.7 A resolution from a single crystal. The unit-cell parameters were a = b = 119.1, c = 270.7 A, alpha = beta = 90, gamma = 120 degrees. Three molecules were predicted to be present in the asymmetric unit from a calculated self-rotation function.

Animals↗
PubMed2006

Danggui buxue tang--a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells.

Danggui buxue tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains radix Astragali (Huangqi; RA) and radix Angelicae Sinensis (Danggui; RAS). The weight ratio of RA to RAS used in DBT must be 5:1 as stipulated as early as AD 1247; however, DBT's mechanism of action has never been described. Here, the estrogenic effects of DBT were investigated by determining the phosphorylations of estrogen receptor alpha (ER alpha) and extracellular signal-regulated kinase 1/2 (Erk1/2) in cultured MCF-7 cells. The application of DBT triggered the phosphorylation of ER alpha and Erk1/2 in a time-dependent manner. In contrast to the effect of estrogen, DBT triggered ER alpha phosphorylation at both S118 and S167. This DBT-specific phosphorylation was not triggered by an extract of one of the individual herbs, or by mixing the extracts of RA and RAS. DBT-induced downstream signals are described here. These signals suggest the uniqueness of this Chinese herbal decoction that requires a well-defined formulation.

Cells, Cultured↗
PubMed2006

A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a 'universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that 'high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways.

Bacterial Physiological Phenomena↗
PubMed2006

Bicyclic carbamates as inhibitors of papain-like cathepsin proteases.

A 6-oxa-1-aza-bicyclo[3.2.1]octan-7-one system inhibits the proteolytic activity of several cysteine proteases belonging to the papain family. In vitro mechanistic studies and in silico calculations suggest that the minimal pi-overlap between the bridgehead nitrogen and the carbonyl leads to a considerable weakening of the urethane system, making it susceptible to nucleophilic attack from the active site thiol group. The resulting covalent adduct is slowly hydrolyzed, releasing the hydroxypiperidine product of the inhibitor. Synthesis and testing of a set of analogs led to variable protease subtype selectivities ranging from micromolar to nanomolar potencies.

Binding Sites↗
PubMed2006

Growth promoting effect of a transgenic Bacillus mucilaginosus on tobacco planting.

In this study, we have investigated the plant growth promoting effect of Bacillus mucilaginosus strain D(4)B(1), a rhizosphere soil organism, and its transgenic strain NKTS-3 on tobacco planting. The transgenic strain contains a phytase expression cassette that can express high active phytase extracellularly and hydrolyze phytate in the soil to liberate inorganic phosphorus for the growth of tobacco plants. Greenhouse study and field experiments showed that both wild-type B. mucilaginosus and the transgenic strain could promote tobacco plant growth. Moreover, the transgenic strain promoted tobacco plant growth (235% more than control in pot experiments and 125% more than control in field experiments) was higher than the wild-type B. mucilaginosus (183% more than control in pot experiments and 108% more than control in field experiments). In addition, the inoculation with transgenic rhizobacteria could significantly improve root acquisition of phosphorus and increase the phosphorus content of the plant.

6-Phytase↗
PubMed2006

The serotonin 5-HT1D receptor gene and attention-deficit hyperactivity disorder in Chinese Han subjects.

Attention-deficit/hyperactivity disorder (ADHD) is a heritable disease. Serotonin is one of the neurotransmitters involved in the etiology of ADHD. Serotonin-1D receptors are autoreceptors which can regulate the release of serotonin in brain, so the HTR1D gene may be predisposing. The current study genotyped two variants of HTR1D gene in 272 ADHD trios of Chinese ethnicity, that is 1350T > C in the coding region and 1236A > G in 3'-UTR by the use of transmission disequilibrium test (TDT). The A allele of the 1236A > G polymorphism exhibited both a trend toward preferential transmission to ADHD probands (chi2 = 3.815, P = 0.051) and a significant preferential transmission to probands of ADHDC (chi2 = 4.198, P = 0.040). Additional polymorphisms in this gene need to be studied further.

Asian People↗
PubMed2006

Production of authentic SARS-CoV M(pro) with enhanced activity: application as a novel tag-cleavage endopeptidase for protein overproduction.

The viral proteases have proven to be the most selective and useful for removing the fusion tags in fusion protein expression systems. As a key enzyme in the viral life-cycle, the main protease (M(pro)) is most attractive for drug design targeting the SARS coronavirus (SARS-CoV), the etiological agent responsible for the outbreak of severe acute respiratory syndrome (SARS) in 2003. In this study, SARS-CoV M(pro) was used to specifically remove the GST tag in a new fusion protein expression system. We report a new method to produce wild-type (WT) SARS-CoV M(pro) with authentic N and C termini, and compare the activity of WT protease with those of three different types of SARS-CoV M(pro) with additional residues at the N or C terminus. Our results show that additional residues at the N terminus, but not at the C terminus, of M(pro) are detrimental to enzyme activity. To explain this, the crystal structures of WT SARS-CoV M(pro) and its complex with a Michael acceptor inhibitor were determined to 1.6 Angstroms and 1.95 Angstroms resolution respectively. These crystal structures reveal that the first residue of this protease is important for sustaining the substrate-binding pocket and inhibitor binding. This study suggests that SARS-CoV M(pro) could serve as a new tag-cleavage endopeptidase for protein overproduction, and the WT SARS-CoV M(pro) is more appropriate for mechanistic characterization and inhibitor design.

Calbindins↗
PubMed2006

A selective cyclooxygenase-2 inhibitor decreases transforming growth factor-beta1 synthesis and matrix production in human peritoneal mesothelial cells.

High glucose concentration, which provides the chief driving force in peritoneal dialysis, has been considered to be an important initial factor that contributes to peritoneal thickening and fibrosis. Human peritoneal mesothelial cells (HPMCs) and the expansion of extracellular matrix (ECM) play important roles in the pathological process of peritoneal fibrosis. Peritoneal matrix accumulation is a characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients with upregulation of transforming growth factor-beta1 (TGF-beta1) in their drained effluent show an increased risk of PF. Inhibition of TGF-beta1 expression in human peritoneal mesothelial cells (HPMCs) may provide a potential treatment for PF. sc58236, a highly selective cyclooxygenase-2 (COX-2) inhibitor, reduces proteinuria and mRNA expression of TGF-beta1 and collagen III and IV in the remnant kidney, but their effects on ECM turnover in HPMCs are unknown. The aims of this study were to investigate the effects of sc58236 on TGF-beta1 expression and matrix production in HPMCs. HPMCs were cultured from human omentum by an enzyme digestion method. To examine the effect of sc58236 on TGF-beta1 and ECM secretion, HPMC were incubated in medium F12 with high concentration of D-glucose (4.25%) in the presence and absence of 20 microM sc58236. The mRNA expression of COX-2, TGF-beta1 and collagen I (Col I) were determined by semi-quantification reverse transcription PCR (RT-PCR). Prostaglandin E2 (PGE2) concentration in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA). The protein of TGF-beta1 was determined by ELISA and the activity of TGF-beta1 present in the conditioned media was measured using the mink lung epithelial cell (MLEC) growth inhibition assay. Proteins of COX-2 and Col were determined by Western blot. The results showed that primary cultures of HPMCs do express the mRNA for COX-2 and stimulation of these cells with 4.25% D-glucose induced a marked increase in COX-2 mRNA expression and protein. PGE2 expression was obviously up-regulated with stimulation by 4.25% D-glucose. Addition of 20 microM sc58236 significantly inhibited PGE2 release into the culture medium. mRNA expression and bioactive and total protein of TGF-beta1 and Col I were significantly increased in HPMCs stimulated with 4.25% D-glucose compared to the control group with F12 media, which was reversed in the presence of sc58236 (20 microM). An obvious decrease in TGF-beta1 mRNA expression and bioactive and total protein were found in sc58236 treated groups compared to the group stimulated with 4.25% D-glucose. Exposure of HPMCs to sc58236 reduced Col I secretion. Sc58236 reduces the expression of TGF-beta1 in HPMCs stimulated by 4.25% D-glucose and reduces ECM production through PGE2 production. These studies suggest that sc58236, a highly selective cyclooxygenase-2 (COX-2) inhibitor, may have a specific role in ameliorating the course of progressive peritoneal fibrosis under long-term peritoneal dialysis states.

Cell Division↗