Biomedical subjects

Jing Li

Publications and source records attributed to Jing Li.

At least 55 records · Page 3Linked to original sources

PubMed2006

A new method for quantifying residue conservation and its applications to the protein folding nucleus.

The conservation of residues in columns of a multiple sequence alignment (MSA) reflects the importance of these residues for maintaining the structure and function of a protein. To date, many scores have been suggested for quantifying residue conservation, but none has achieved the full rigor both in biology and statistics. In this paper, we present a new approach for measuring the evolutionary conservation at aligned positions. Our conservation measure is related to the logarithmic probabilities for aligned positions, and combines the physicochemical properties and the frequencies of amino acids. Such a measure is both biologically and statistically meaningful. For testing the relationship between an amino acid's evolutionary conservation and its role in the Phi-value defined protein folding kinetics, our results indicate that the folding nucleus residues may not be significantly more conserved than other residues by using the biological-relevance weighted statistical scoring method suggested in this paper as an alternative to entropy-based procedures.

Amino Acid Sequence↗

PubMed2006

Visual mismatch negativity elicited by facial expressions under non-attentional condition.

A modified "cross-modal delayed response" paradigm was used to investigate putative processing of face expression in the absence of focused attention to the face. Neutral, happy and sad faces were presented during intervals occurring between a tone and a response imperative signal (a faint click), while subjects were instructed to discriminate the location of the tone as quickly and accurately as possible and to ignore the faces. A neutral face was presented in 80% of the trials whereas the happy and sad faces were presented in the remaining trials - 10%, respectively. Expression mismatch negativity (EMMN) was obtained by subtracting the ERP elicited by neutral faces from that elicited by sad faces or happy faces. The EMMN started from around 120 ms (sad) and 110 ms (happy) lasting up to 430 ms (sad) and 360 ms (happy) post-stimulus. The EMMN elicited by sad faces was more negative than that elicited by happy faces. Both EMMNs distributed over posterior areas and covered larger areas in the right than in the left hemisphere sites (especially for happy EMMN).

Adult↗

PubMed2006

Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways.

Neurotensin (NT), a gut peptide, plays important roles in gastrointestinal secretion, inflammation, and growth of normal and neoplastic tissues. cAMP regulates the secretion of hormones via its effector proteins protein kinase A (PKA) or Epac (exchange protein directly activated by cAMP). The small GTPase Rap1 can be activated by both PKA and Epac; however, the role of Rap1 in hormone secretion is unknown. Here, using the BON human endocrine cell line, we found that forskolin (FSK)-stimulated NT secretion was reduced by inhibition of Rap1 expression and activity. FSK-stimulated NT secretion was enhanced by overexpression of either wild-type or constitutively active Rap1. Epac activators and wild-type Epac enhanced NT release and Rap1 activity. In contrast, overexpression of a cAMP binding mutant, EpacR279E, decreased NT release and Rap1 activity. PKA activation increased NT release and Rap1 activity. FSK-stimulated NT release was reduced by PKA inhibition and the dominant negative Rap1N17. NT secretion, stimulated by Epac activation, was reduced by PKA inhibition; NT release, stimulated by PKA activation, was enhanced by wild-type Epac but reduced by the mutant EpacR279E. Finally, prostaglandin E2 (PGE2), a physiological agent that increases cAMP, stimulated NT secretion via cAMP/PKA/Rap1. Importantly, we demonstrate that PKA and Epac mediate the cAMP-induced NT secretion synergistically by converging at the common downstream target protein Rap1. Moreover, PGE2, a potent mediator of inflammation and associated with colorectal carcinogenesis, stimulates NT release suggesting a possible link between PGE2 and NT on intestinal inflammatory disorders and colorectal cancers.

Cell Line, Tumor↗

PubMed2006

EARLY RESPONSIVE TO DEHYDRATION 15, a negative regulator of abscisic acid responses in Arabidopsis.

EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15) is rapidly induced in response to various abiotic and biotic stress stimuli in Arabidopsis (Arabidopsis thaliana). Modulation of ERD15 levels by overexpression or RNAi silencing altered the responsiveness of the transgenic plants to the phytohormone abscisic acid (ABA). Overexpression of ERD15 reduced the ABA sensitivity of Arabidopsis manifested in decreased drought tolerance and in impaired ability of the plants to increase their freezing tolerance in response to this hormone. In contrast, RNAi silencing of ERD15 resulted in plants that were hypersensitive to ABA and showed improved tolerance to both drought and freezing, as well as impaired seed germination in the presence of ABA. The modulation of ERD15 levels not only affected abiotic stress tolerance but also disease resistance: ERD15 overexpression plants showed improved resistance to the bacterial necrotroph Erwinia carotovora subsp. carotovora accompanied with enhanced induction of marker genes for systemic acquired resistance. We propose that ERD15 is a novel mediator of stress-related ABA signaling in Arabidopsis.

Abscisic Acid↗

PubMed2006

[Mechanism of post-stroke reflex sympathetic dystrophy: study with needle electromyography].

OBJECTIVE: To explore the mechanism of post-stroke reflex sympathetic dystrophy (RSD) patients electromyographic abnormality and confirm its clinical value. METHODS: Fifty patients with first-onset stroke, aged 33 - 78, including 30 with RSD and 20 without RSD, underwent needle electromyography (EMG) to test the nerve conduction velocity (NCV) and sensory nerve conduction velocity (SCV) of bilateral median nerves, and the number and position of spontaneous EMG activity of bilateral short abductor muscles of thumb and abductor muscles little finger. RESULTS: The median nerve compound muscle action potential (CMAP) amplitude of the affected upper extremities of the RSD group was 8.6 mV +/- 2.9 mV, significantly lower than that of the non-RSD group (13.2 mV +/- 4.6 mV, P < 0.01). The incidence of spontaneous electrical potential of the RSD group was 100%; significantly higher than hat of the non-RSD group (65%, P < 0.001). The quantity of spontaneous EMG activity on the short abductor muscles of thumb and abductor muscles little finger was increased in the RSD group (P < 0.01). The motor nerve conduction velocity and electrophysiological presentation of sensory nerve of these 2 groups were all normal and without significant differences between them. CONCLUSION: Partial axonal degeneration occurs on the distal motor never fibers of the affected upper extremity of the RSD patients, which may be related to subsequent peripheral nerve injury after central nerve system impairment.

Adult↗

PubMed2006

Pharmacokinetics, absorption and tissue distribution of tanshinone IIA solid dispersion.

This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of tanshinone IIA, a highly lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic characteristics, absolute bioavailability, tissue distribution and plasma protein binding properties were determined. The membrane permeability was evaluated using Caco-2 cells in monolayer. The pharmacokinetic plasma profile of tanshinone IIA after a single intravenous dosing exhibited a triexponential pattern consisting of rapid distribution (t1/2 alpha, 0.024 h), slow redistribution (t1/2 beta, 0.34 h) and terminal elimination phase (t1/2 gamma, 7.5 h). Tanshinone IIA preferentially distributed into the reticuloendothelial system, especially into liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %) bound highly to plasma proteins, among which lipoprotein played an important role (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that the AUC and Cmax increased less proportionally to dose and Tmax was significantly prolonged. The poor absorption of tanshinone IIA may be caused by its low aqueous solubility and limited membrane permeability. There were no significant differences of the apparent permeability coefficient for all tested concentrations and for the apical to basolateral and reverse direction transport, suggesting a passive transport mode and no involvement of an efflux protein. In conclusion, tanshinone IIA has a suitable pharmacokinetic behavior except for its poor absorption. A pharmaceutical strategy for promoting its absorption should be designed to develop tanshinone IIA as a new drug candidate.

Abietanes↗

PubMed2006

Identification and analysis of the mouse basic/Helix-Loop-Helix transcription factor family.

The basic/Helix-Loop-Helix (bHLH) proteins are a family of transcription factors that regulates a variety of biological processes. Based on a previously defined consensus motif, we identified the complete set of bHLH protein family from the mouse proteome databases and carried out a series of bioinformatics analysis. As results, 124 mouse bHLH proteins were identified in this study, and 28 of them were additional bHLH proteins beyond the previous report. These 124 mouse bHLH proteins were classified into groups from A to F by the nomenclature and phylogenetic analysis. Statistic analysis of the Gene Ontology annotation of these proteins showed that the bHLH proteins tend to perform functions related to cell differentiation and development. Gene function enrichment analysis among six groups illuminated that the proteins in certain group tend to have special biology functions, so that the molecular function of the uncharacterized proteins in groups could be inferred.

Amino Acid Sequence↗

PubMed2006

Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling.

Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas.

Apoptosis↗

PubMed2006

Poly(gamma,L-glutamic acid)-cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice.

An easily administered cis-dichlorodiammineplatinum (II) (CDDP) formulation with less toxicity and greater antitumor effect would be extremely valuable. We describe PGA-CDDP, a water-soluble CDDP derivative. The hydrolyzed gamma-PGA has a molecular weight between 45 and 60 kDa, and is a water-soluble, biodegradable, and nontoxic polymer produced by microbial fermentation. CDDP can be released from the resulting conjugate in PBS: there was initially a burst release during the first 6h, followed by sustained release. In vitro, PGA-CDDP was less potent than free CDDP at inhibiting cell growth in the Bcap-37 cell line. PGA-CDDP was given as 3 doses at an equivalent CDDP dose of 4 or 12 mg/kg with 2-day intervals between injections to Bcap-37-grafted mice. This treatment showed stronger antitumor activity and was less toxic than CDDP in vivo. Antitumor activity assays demonstrated that the PGA-CDDP conjugate treatment had significantly higher antitumor activity than control PBS treatment (P<0.01). PGA-CDDP also increased the survival of mice bearing Bcap-37 cells with reference to PBS treatment or free CDDP treatment. Furthermore, mice treated with PGA-CDDP (4 mg/kg, administered on day 0 and 5) showed no body weight loss (P>0.05 with respect to PBS treatment), whereas free CDDP treatment at the same dose caused a body weight loss of 20-30% (P<0.001). These findings suggest that PGA produced by microbial fermentation may be used as an effective drug carrier for CDDP and that PGA-CDDP may have potential applications in the treatment of human breast cancer.

Animals↗

PubMed2006

Novel genes encoding six kinds of three-finger toxins in Ophiophagus hannah (king cobra) and function characterization of two recombinant long-chain neurotoxins.

Three-finger toxins are a family of low-molecular-mass toxins (<10 kDa) having very similar three-dimensional structures. In the present study, 19 novel cDNAs coding three-finger toxins were cloned from the venom gland of Ophiophagus hannah (king cobra). Alignment analysis showed that the putative peptides could be divided into six kinds of three-finger toxins: LNTXs (long-chain neurotoxins), short-chain neurotoxins, cardiotoxins (CTXs), weak neurotoxins, muscarinic toxins and a toxin with a free SH group. Furthermore, a phylogenetic tree was established on the basis of the toxin cDNAs and the previously reported similar nucleotide sequences from the same source venom. It indicated that three-finger-toxin genes in O. hannah diverged early in the course of evolution by long- and short-type pathways. Two LNTXs, namely rLNTX1 (recombinant LNTX1) and rLNTX3, were expressed and showed cytolytic activity in addition to their neurotoxic function. By comparing the functional residues, we offer some possible explanations for the differences in their neurotoxic function. Moreover, a plausible elucidation of the additonal cytolytic activity was achieved by hydropathy-profile analysis. This, to our knowledge, is the first observation that recombinant long chain alpha-neurotoxins have a CTX-like cytolytic activity.

Amino Acid Sequence↗

PubMed2006

Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis.

Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as promising agents for cancer therapy. Recently, heparanase inhibitors have offered a new avenue for such work because heparanase is thought to be critically involved in the metastatic and angiogenic potentials of tumor cells. Here, we report that oligomannurarate sulfate (JG3), a novel marine-derived oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3 significantly inhibited tumor angiogenesis and metastasis, both in vitro and in vivo, by combating heparanase activity via binding to the KKDC and QPLK domains of the heparanase molecule. The JG3-heparanase interaction was competitively inhibited by low molecular weight heparin (4,000 Da) but not by other glycosaminoglycans. In addition, JG3 abolished heparanase-driven invasion, inhibited the release of heparan sulfate-sequestered basic fibroblast growth factor (bFGF) from the extracellular matrix, and repressed subsequent angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and extracellular signal-regulated kinase 1/2 phosphorylation and blocked bFGF-triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to inhibit both major heparanase activities by simultaneously acting as a substrate mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest that JG3 should be considered as a promising candidate agent for cancer therapy.

Allantois↗

PubMed2006

Immunization of mice with T cell-dependent antigens promotes IL-6 and TNF-alpha production in muscle cells.

IL-6 and TNF-alpha are proinflammatory cytokines involved in various inflammatory or non-inflammatory disorders characterized by muscle wasting. While infiltrating leukocytes are known to be the major source of these cytokines, it is unclear whether muscle cells also contribute to local inflammation. In this study, we first showed that cultured muscle cells and naive mouse muscle tissue were capable of producing IL-6 and TNF-alpha. We demonstrated an increased expression of IL-6 and TNF-alpha on muscle sections of C57BL/6J mice immunized with acetylcholine receptor (AChR) in the complete Freund's adjuvant (CFA) or with CFA only. In the presence of IL-6 or TNF-alpha, cultured AChR-expressing mouse (G-8) and human (TE671) skeletal muscle cells showed significantly decreased alpha-bungarotoxin-binding sites as measured by cellular ELISA. Moreover, IL-6- or TNF-alpha-treated muscle cells displayed a considerable increase in apoptotic cell ratios. Collectively, this study suggests a direct role for these two cytokines in muscle cell destruction and a possibility of muscle cell damage via an autocrine fashion.

Animals↗

PubMed2006

[Expression of calmodulin in the articular process of vertebrae of adolescent idiopathic scoliosis patients].

OBJECTIVE: To investigate the expression of calmodulin in the articular process of vertebrae of adolescent idiopathic scoliosis (AIS) patients and congenital scoliosis (CS) patients and its possible effects on the pathogenesis of AIS. METHODS: Nine AIS patients aged 13 - 17, and 10 patients of CS, aged 11 - 18, underwent orthopedic surgery. Specimens of the inferior articular process from the apical vertebrae and upper end vertebrae discarded during operation were collected from the AIS patients and specimens of the. Inferior articular process from the upper end vertebrae wee collected from the CS patients. Immunohistochemistry was used to detect the protein expression of calmodulin, and in situ hybridization was adopted to examine the mRNA expression of calmodulin. RESULTS: Calmodulin were expressed in the bone cells. There was no difference between the expression of calmodulin at the concave side and convex side, or between the apical vertebrae and end vertebrae. The expression of calmodulin of the AIS group was significant lower than that of the CS group (P < 0.05). The result of immunohistochemistry and that of in situ hybridization corresponded with each other. CONCLUSION: The expression of calmodulin in the articular process of vertebrae of AIS patients is low, suggesting that it plays a role in the development and progression of AIS.

Adolescent↗

PubMed2006

HSP70 gene fused with Hantavirus S segment DNA significantly enhances the DNA vaccine potency against hantaviral nucleocapsid protein in vivo.

Heat shock proteins (HSPs) have been shown to act as adjuvants when coadministered with peptide antigens or given as fusion proteins and enhance the vaccination efficiency. To evaluate the enhancement of the potency of Hantaan virus (HTNV) nucleocapsid protein (NP) immunogenicity by heat shock protein 70 (HSP70), we developed a novel chimeric HTNV S-HSP70 DNA vaccine plasmid by genetically linking HSP70 gene to the full-length HTNV S segment DNA (HTNV S DNA). C57BL/6 mice were immunized with this plasmid followed by a subsequent boost with homologous recombinant protein. The levels of HTNV NP-specific antibody and cellular immune response were measured by use of ELISA, fluorescence activated cell sorter (FACS) analysis, cytotoxicity assay, and IFN-gamma ELISPOT assay. We found that HTNV S-HSP70 DNA vaccination significantly increased the levels of HTNV NP-specific antibody, IgG2a/IgG1 ratio, IFN-gamma producing CD8+ T-cell precursor frequencies, and cytotoxic T lymphocyte (CTL) response when compared with immunization with HTNV S DNA alone or HTNV S DNA physically mixed with HSP70 DNA. By contrast, HSP70 DNA or vector DNA immunization could not induce appreciable levels of specific antibodies and CTL response. Thus, we demonstrate for the first time that HSP70-based HTNV S DNA can induce both humoral and cellular immune response specific for HTNV NP and is a promising candidate DNA vaccine for HTNV infection.

Animals↗

PubMed2006

Overexpression of wild-type PKD2 leads to increased proliferation and invasion of BON endocrine cells.

Carcinoid tumors are rare neuroendocrine tumors with a predilection for the gastrointestinal tract. Protein kinase D (PKD), a novel serine/threonine protein kinase, has been implicated in the regulation of transport processes in certain cell types. We have reported an important role for PKD in stimulated peptide secretion from a human (BON) carcinoid cell line; however, the role of PKD isoforms, including PKD2, in the proliferation and invasion of carcinoid tumors remains unclear. In the present study, we found that overexpression of PKD2 by stable transfection of BON cells with PKD2-wild type (PKD2WT) significantly increased proliferation and invasion compared to cells transfected with PKD2-kinase dead (PKD2KD) or pcDNA3 (control). Similarly, inhibition of PKD2 activity with small interfering RNA (siRNA) significantly decreased proliferation and invasion compared to cells transfected with non-targeting control (NTC) siRNA. These data support an important role for PKD2 in carcinoid tumor progression. Targeted inhibition of the PKD family may prove to be a novel treatment option for patients with carcinoid tumors.

Carcinoid Tumor↗

PubMed2006

Retinal vascular abnormalities in adult Chinese in rural and urban Beijing: the Beijing Eye Study.

OBJECTIVE: To assess retinal vascular abnormalities, including focal and generalized arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing, in adult Chinese in rural and urban Beijing, and their associations with self-reported diagnosis of cardiovascular and cerebrovascular diseases. DESIGN: Population-based cross-sectional cohort study. PARTICIPANTS: The study included 4439 subjects out of 5324 subjects invited to participate (response rate, 83.4%) with an age of > or =40 years. It was divided into a rural part (n = 1973 [44.4%]) and an urban part (n = 2466 [55.6%]). Mean age was 56.2+/-10.6 years (range, 40-101 years). METHODS: Color optic disc photographs were morphometrically examined. One eye of each participant was randomly selected. Generalized and focal arteriolar narrowing, arteriovenous nicking (arteriovenous crossing abnormalities), and arteriolar sheathing were assessed. Self-reported histories of cardiovascular and cerebrovascular diseases and habits of smoking and alcohol drinking were obtained from questionnaires. MAIN OUTCOME MEASURES: Frequency of generalized and focal arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing. RESULTS: Optic disc photographs were available for 4228 (95.2%) subjects. Focal arteriolar narrowing was found in 6.3%, arteriovenous nicking in 6.6%, arteriolar sheathing in 4.8%, and generalized narrowing in 4.3% of the subjects. Abnormalities were more common in the temporal quadrant; they were rare in the inferior nasal quadrant. Frequencies and severities of all retinal microvascular abnormalities examined increased with age (P<0.05). The microvascular abnormalities were detected more frequently in the rural population than in the urban population (P<0.05). After controlling for age, gender, area, and habit of drinking alcohol, generalized arteriolar narrowing (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.64, 4.22), focal arteriolar narrowing (OR, 1.51; 95% CI, 1.00, 2.29), and arteriolar sheathing (OR, 1.71; 95% CI, 1.08, 2.71) were significantly associated with the self-reported diagnosis of arterial hypertension. The microvascular abnormalities were not significantly associated with the self-reported diagnosis of coronary heart disease or stroke. CONCLUSIONS: Retinal vascular abnormalities in adult Chinese increase with age and are more commonly found in people living in rural areas. Retinal vascular abnormalities are associated with the self-reported diagnosis of arterial hypertension, and are not related to self-reported diagnosis of coronary heart disease or previous cerebrovascular events such as stroke.

Adult↗

PubMed2006

Calmodulin isoform-specific activation of a rice calmodulin-binding kinase conferred by only three amino-acids of OsCaM61.

The kinase activity of a Ca(2+)/calmodulin (CaM)-binding serine/threonine protein kinase from rice (Oryza sativa) (OsCBK) has been reported to be unaffected by OsCaM1 binding. In this study, we examined whether other rice CaMs can stimulate OsCBK. It was observed that OsCaM61 stimulated OsCBK in a Ca(2+)-dependent manner. In addition, Ala(111), Gly(123) and Ser(127) were identified as critical residues for OsCBK activation. Mutational study and fluorescent spectroscopy analysis indicated that CaM-binding affinity does not correlate with the kinase activity and that these key amino-acids in OsCaM61 play a vital role in suitable changes of OsCBK conformation for kinase activation.

Alanine↗

PubMed2006

The hpa1 mutant of Arabidopsis reveals a crucial role of histidine homeostasis in root meristem maintenance.

Histidine (His) is an essential ingredient for protein synthesis and is required by all living organisms. In higher plants, although there is considerable evidence that His is essential for plant growth and survival, there is very little information as to whether it plays any specific role in plant development. Here, we present evidence for such a role of this amino acid in root development in Arabidopsis (Arabidopsis thaliana) from the characterization of a novel Arabidopsis mutant, hpa1, which has a very short root system and carries a mutation in one of the two Arabidopsis histidinol-phosphate aminotransferase (HPA) genes, AtHPA1. We have established that AtHPA1 encodes a functional HPA and that its complete knockout is embryo lethal. Biochemical analysis shows that the mutation in hpa1 only resulted in a 30% reduction in free His content and had no significant impact on the total His content. It did not cause any known symptoms of His starvation. However, the mutant displayed a specific developmental defect in root meristem maintenance and was unable to sustain primary root growth 2 d after germination. We have demonstrated that the root meristem failure in the mutant is tightly linked to the reduction in free His content and could be rescued by either exogenous His supplementation or AtHPA1 overexpression. Our results therefore reveal an important role of His homeostasis in plant development.

Amino Acid Sequence↗