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Biomedical subjects

Ming Li

Publications and source records attributed to Ming Li.

At least 55 records · Page 3Linked to original sources

Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-kappaB and AP-1 pathways.

B lymphocytes are generally considered to be the only source of immunoglobulins. However, increasing evidence revealed that some human epithelial cancer cell lines, including nasopharyngeal carcinoma (NPC) cell lines, expressed immunoglobulins. Moreover, we previously found that expression of kappa light chain in NPC cells could be upregulated by EBV-encoded latent membrane protein 1 (LMP1). Here, Western blot and flow cytometric analysis of intracellular kappa staining indicated that upregulation of the expression of kappa was inhibited by using LMP1-targeted DNAzyme and that Bay11-7082 and SP600125, inhibitors of JNK and NF-kappaB, respectively, inhibited LMP1-augmented kappa light chain expression in NPC cells. LMP1-positive NPC cells expressing the dominant-negative mutant of IkappaBalpha (DNMIkappaBalpha) or of c-Jun (TAM67) exhibited significantly decreasing kappa production compared with their parental cells. These results suggest that LMP1 elevated kappa light chain through activation of the NF-kappaB and AP-1 signaling pathways. The present study provided some hints of possible mechanisms by which human cancer cells of epithelial origin produced immunoglobulins.

Cell Line, Tumor↗

Neural stem cells: isolation and differentiation into cholinergic neurons.

This investigation aimed to isolate neural stem cells from neonatal hippocampus and induce them to differentiate into cholinergic neurons. The isolated neural stem cells were incubated in serum-free Dulbecco's modified Eagle medium/F12 medium added with 20 ng/ml basic fibroblast growth factor and B27. The cell line isolated from the hippocampal formation of neonatal rats expressed nestin and had the potency to form clones and differentiate into neurons, astrocytes and oligodendrocytes. Embryonic chick skeletal muscle extract was used to induce the differentiation of the neural stem cells into cholinergic neurons. Immunocytochemistry was used to detect the choline acetyltransferase antigen of cholinergic neurons for confirmation. The results showed that embryonic chick skeletal muscle extract could induce isolated neural stem cell to differentiate into a significantly larger number of cholinergic neurons than controls.

Animals↗

Perfluorooctanesulfonate and periluorooctanoate in red panda and giant panda from China.

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are important perfluorochemicals (PFCs) in various applications. Recently, it has been shown that these compounds are widespread in the environment, wildlife, and humans. The giant panda and the red panda belong to the order Carnivora, but are highly specialized as bamboo feeders. Both species are considered rare and endangered. In this study, we report for the first time on levels of PFOS and PFOA in serum of the giant panda and the red panda captured in zoos and animal parks from six provinces in China. PFOS was the predominant compound in all panda samples measured (ranging from 0.80 to 73.80 microg/L for red panda and from 0.76 to 19.00 microg/L for giant panda). The PFOA level ranged from 0.33 to 8.20 microg/L for red panda, and from 0.32 to 1.56 microg/L for giant panda. There was a positive significant correlation between concentrations of PFOS and PFOA in the serum obtained from pandas. No age- or sex- related differences were observed in concentrations of the fluorochemicals in panda sera. Greater concentrations of the fluorochemicals were found for those individuals collected from zoos near urbanized or industrialized areas than for other areas. These data combined with other reported data suggest that there are large differences in distribution of perfluorinated compounds in terrestrial animals.

Age Factors↗

Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa.

A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

Gene Products, env↗

CD100 enhances dendritic cell and CD4+ cell activation leading to pathogenetic humoral responses and immune complex glomerulonephritis.

CD100, a member of the semaphorin family, is a costimulatory molecule in adaptive immune responses by switching off CD72's negative signals. However, CD100's potential pathogenetic effects in damaging immune responses remain largely unexplored. We tested the hypothesis that CD100 plays a pathogenetic role in experimental immune complex glomerulonephritis. Daily injection of horse apoferritin for 14 days induced immune complex formation, mesangial proliferative glomerulonephritis and proteinuria in CD100-intact (CD100+/+) BALB/c mice. CD100-deficient (CD100-/-) mice were protected from histological and functional glomerular injury. They exhibited reduced deposition of Igs and C3 in glomeruli, reduced MCP-1 and MIP-2 intrarenal mRNA expression, and diminished glomerular macrophage accumulation. Attenuated glomerular injury was associated with decreased Ag-specific Ig production, reduced CD4+ cell activation and cytokine production. Following Ag injection, CD4+ cell CD100 expression was enhanced and dendritic cell CD86 expression was up-regulated. However, in CD100-/- mice, dendritic cell CD86 (but not CD80) up-regulation was significantly attenuated. Following i.p. immunization, CD86, but not CD80, promotes early Ag-specific TCR-transgenic DO11.10 CD4+ cell proliferation and IFN-gamma production, suggesting that CD100 expression enables full expression of CD86 and consequent CD4+ cell activation. Transfer of CD100+/+ DO11.10 cells into CD100-/- mice resulted in decreased proliferation demonstrating that CD100 from other sources in addition to CD100 from Ag-specific CD4+ cells plays a role in initial T cell proliferation. Although T cell-B cell interactions also may be relevant, these studies demonstrate that CD100 enhances pathogenetic humoral immune responses and promotes the activation of APCs by up-regulating CD86 expression.

Animals↗

Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV.

BACKGROUND: Before the onset of AIDS, replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in the lungs is considered to be latent. When and how virus replication is controlled in the lungs is unclear. In the present study, we examine virus replication in the lungs and in cells recovered from bronchoalveolar lavage (BAL) samples in a comprehensive, longitudinal analysis of an SIV/macaque model. METHODS: Gene-specific RNA and DNA were quantitated by polymerase chain reaction (PCR) and by real-time reverse-transcription PCR (RT-PCR). Alveolar macrophages were isolated using Dynabeads CD14 (Invitrogen). Expression of CCAAT/enhancer-binding protein beta (C/EBP beta ) isoforms was examined by Western blot analysis. RESULTS: SIV replication occurred in the lungs during acute infection and correlated with plasma viral load. Innate immune responses involving interferon- beta and the dominant-negative isoform of C/EBP beta were induced at this time. SIV RNA expression was suppressed in the lungs during asymptomatic infection, when no correlation existed with plasma viral load until SIV RNA levels rebounded again during late-stage disease. Modulation of viral RNA levels in BAL cells reflected RNA levels in lung tissue throughout each phase of infection. CONCLUSION: Quantitation of SIV RNA in BAL cells provides a consistent surrogate assessment of virus replication in lung tissue. Innate immune responses contribute to compartmentalized suppression of acute SIV replication in the lungs.

Animals↗

Sequence analysis of a canine parvovirus isolated from a red panda (Ailurus fulgens) in China.

Canine parvovirus (CPV) was first recognized in the late 1970 s in dogs and has mutated and spread throughout the world in canid and felid species since then. In this study, a novel CPV was isolated from the endangered red panda (Ailurus fulgens) in China. Nucleotide and phylogenetic analysis of the capsid protein VP2 gene classified the red panda parvovirus (RPPV) as a CPV-2a type. Substitution of Val for Gly at the conserved 300 residue in RPPV presents an unusual variation in the CPV-2a amino acid sequence and is further evidence for the continuing evolution of the virus. The 300 residue is important in distinguishing the antigenicity and host range of CPVs. The clinical significance and population impact of RPPV infection in captive red pandas in China is unknown and is an important topic for future research.

Ailuridae↗

Synthesis and cytotoxicities of dioscin derivatives with decorated chacotriosyl residues.

Two series of dioscin derivatives (4a-o and 5a-o) with selected modifications at the 6' and 4''' positions of the chacotriosyl residue, respectively, were synthesized. All the 6'-N-acyl-dioscin derivatives did not show considerable inhibitory activities at 10 microM, while most of the 4'''-O-(2-N-acyl)ethyl-dioscin derivatives behaved as potent as dioscin, against the growth of tumor cells.

Cell Line, Tumor↗

[Antimicrobial peptide may originate from hemoglobin and play a role in the antibacterial mechanisms of endometrium].

OBJECTIVE: To isolate and purify antimicrobial peptides from human uterus mucus. METHODS: Acid-soluble extract was obtained from the specimens of endometrium mucus from 3 hysteromyomas patients during total hysterectomy. Acidic urea-polyacrylamide gel electrophoresis was used to analyze the acidic extract. The corresponding antimicrobial band HUP was further isolated and purified by electrophoretic elution and reversed-phase high-performance liquid chromatography (RP-HPLC). The antimicrobial activity of the fractions was analyzed by agarose radial diffusion assay. The molecular weight was determined by Tricine-SDS-PAGE. According to the results of the N-terminal sequencing and Mass Spectrometry analysis, the amino acid sequences of the purified molecules were deduced. The deduced amino acid sequence of the antibacterial fragment was further analyzed by ExPASy and OMIGA softwares. RESULTS: An antibacterial peptide named HUP-39 was purified from the human uterine mucus with a molecular weight of 6.777 Ku. N-terminal sequencing and Mass Spectrometry analysis suggested that this antimicrobial peptide should be hHEM-alpha 33-95 amino acid fragment. ExPASy and OMIGA analysis showed that it contained 3alpha-helical transmembrane domains and its pI was 8.38. The fragment was mainly against Escherichia coli ML-35p, E. coli ATCC 25 922, and the clinically isolated strain E. coli 54 080. CONCLUSION: An antimicrobial peptide has been isolated and purified from human uterine mucus, a hHEM-alpha 33-95 amino acid fragment. The antimicrobial molecule in the uterine mucus originates not only from epithelial cells and leucocytes, but also from erythrocytes.

Amino Acid Sequence↗

[Adriamycin and mitomycin dose-dependently downregulate X-kinked inhibitor of apoptosis protein in human bladder cancer cells].

OBJECTIVE: To investigate the efficacy of inducing apoptosis in human bladder cancer cells by adriamycin and mitomycin and relevant mechanism. METHODS: Human bladder cancer cells of the lines RT4, MGH-U1, FJ, and T24 were cultured. Adriamycin of the concentrations of 0.1, 1, and 10 microg/ml, and mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml were added into the culture fluid respectively. CCK-8 colorimetric assay was used to detect the survival rates of the cells so as to select the cell line sensitive and tolerable to the drugs. Flow cytometry was used to detect the cell apoptosis. Western blotting was used to detect the levels of X-kinked inhibitor of apoptosis protein (XIAP) and the cleavage of caspase-3 precursor. RESULTS: It was found that RT4 cells were the most sensitive and the T24 cells were the most tolerable to adriamycin and mitomycin. Treated with adriamycin of the concentrations of 0.1, 1, and 10 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 15.3% +/- 4.3%, 29.3% +/- 6.4%, and 45.0% +/- 5.5% respectively; and the apoptotic rates of the T24 cells were 7.3% +/- 3.1%, 12.5% +/- 4.3%, and 18.2% +/- 6.3% respectively, all significantly lower than those of the RT4 cells (P < 0.05 or P < 0.01). Treated with mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 12.7% +/- 2.9%, 31.3% +/- 4.4%, and 48.9% +/- 5.8% respectively, and the apoptotic rates of the RT4 cells were 7.2% +/- 3.3%, 15.5% +/- 5.2%, and 21.2% +/- 4.4% respectively, all significantly lower than those of the RT4 cells (all P < 0.05). The XIAP expression was not significantly different in these 4 cell lines before the adriamycin and mitomycin treatment. After the treatment of adriamycin and mitomycin, the expression of XIAP was down-regulated dose-dependently, however, being weaker in the T24 cells than in the RT4 cells; and caspase-3 precursor cleavage was enhanced, however, being weaker in the T24 cells too. CONCLUSION: Adriamycin and mitomycin dose-dependently kill the human bladder cancer cells. Such cytotoxic effect may be realized through inducing the cell apoptosis which is associated with the down-regulation of XIAP and cleavage of caspase-3 precursor.

Antibiotics, Antineoplastic↗

The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture.

Mouse spleens contain three populations of conventional (CD11c(high)) dendritic cells (DCs) that play distinct functions. The CD8(+) DC are unique in that they can present exogenous antigens on their MHC class I molecules, a process known as cross-presentation. It is unclear whether this special ability is because only the CD8(+) DC can capture the antigens used in cross-presentation assays, or because this is the only DC population that possesses specialized machinery for cross-presentation. To solve this important question we examined the splenic DC subsets for their ability to both present via MHC class II molecules and cross-present via MHC class I using four different forms of the model antigen ovalbumin (OVA). These forms include a cell-associated form, a soluble form, OVA expressed in bacteria, or OVA bound to latex beads. With the exception of bacterial antigen, which was poorly cross-presented by all DC, all antigenic forms were cross-presented much more efficiently by the CD8(+) DC. This pattern could not be attributed simply to a difference in antigen capture because all DC subsets presented the antigen via MHC class II. Indeed, direct assessments of endocytosis showed that CD8(+) and CD8(-) DC captured comparable amounts of soluble and bead-associated antigen, yet only the CD8(+) DC cross-presented these antigenic forms. Our results indicate that cross-presentation requires specialized machinery that is expressed by CD8(+) DC but largely absent from CD8(-) DC. This conclusion has important implications for the design of vaccination strategies based on antigen targeting to DC.

Animals↗

Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart.

Heart failure is correlated with attenuation of parasympathetic nervous function and enhanced sympathetic activity. Carvedilol, a third-generation beta-blocker, may improve the prognosis of heart failure better than selective beta(1)-blockers. Not all of its effects, however, can be explained by direct actions on the sympathetic nervous system. This study was therefore performed to investigate the possible alterations of muscarinic cholinergic (M)(2) receptors and cholinesterase-positive nerves in different regions of the adriamycin-induced failing rat heart, and the potential effects of carvedilol on these M(2) receptors and cholinesterase-positive nerves. Karnovsky-Roots histochemical staining combined with point counting methods, and immunochemical streptavidin-biotin complex staining and image analysis were used to test the distribution of cholinesterase-positive nerves and the expression of M(2) receptors, respectively. Our results show that the cholinesterase-positive nerve system was downregulated in the adriamycin-induced failing heart group, while the density of M(2) receptors was increased in the carvedilol 3- and 10-mg/kg body weight groups, especially in the endocardial tissues of the left-ventricular free wall. It is concluded that upregulation of M(2) receptors may be one of the potential mechanisms by which carvedilol exert its action on heart failure.

Adrenergic alpha-Antagonists↗

Repair of infarcted myocardium by an extract of Geum japonicum with dual effects on angiogenesis and myogenesis.

BACKGROUND: It has become apparent recently that cardiac myocytes can divide after myocardial infarction, a circumstance that challenges the orthodox view that myocytes may be terminally differentiated. Replacement of the necrosed heart tissue by newly regenerated functional myocardium is a therapeutic ideal, but attempts to reconstitute functional myocardia and coronary vessels have been less successful. METHODS: We isolated a fraction containing 5 compounds from the Chinese herb Geum japonicum, which stimulates the processes of angiogenesis and cardiomyogenesis. We investigated these dual properties in both ex vivo and in vivo systems. RESULTS: We observed that this bioactive fraction displayed favorable dual actions on early angiogenesis and cardiomyogenesis in acute myocardial infarction in an animal model. Our results demonstrated that application of this bioactive fraction showed pronounced effects on limiting infarct size by 35%-45%, stimulating early development of new blood vessels in 24 h, and regenerating myocardium, replacing approximately 49% of the total infarction volume after 2 weeks. Echocardiographic studies demonstrated marked improvement of left ventricular function within 2 days after infarction, and the improvement was sustained for >1 month. CONCLUSIONS: The properties of this bioactive fraction appear to be entirely novel and represent a new approach for the treatment of ischemic heart disease.

Animals↗

Ala45Thr variation in neuroD1 gene is associated with early-onset type 2 diabetes with or without diabetic pedigree in Chinese.

OBJECTIVE: Based on onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous type 2 diabetes mellitus (T2DM), we investigated the Ala45Thr variation in unrelated early-onset and late-onset T2DM with or without diabetic pedigree and unrelated non-diabetic control subjects in Chinese. METHODS: 175 early-onset and 194 late-onset type 2 diabetic patients were further divided into two subgroups according to with or without diabetic pedigree respectively. This NeuroD1-Ala45Thr variation were screened by PCR-direct sequencing in above 369 type 2 diabetic patients and 87 unrelated non-diabetic control subjects. We then compared the distribution of the Ala45Thr variation among the groups, searching for the predictive trends. RESULTS: Frequencies of the variant (AA + GA genotype) in early-onset T2DM are obviously elevated, especially among diabetic pedigree subjects when compared to non-diabetic controls (p= 0.003) and late-onset T2DM subjects (p = 0.014). However, no significant differences were observed between late-onset T2DM with or without diabetic pedigree and non-diabetic control subjects. CONCLUSIONS: Our results suggest that 1) the NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese; 2) the Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese; and 3) onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous T2DM in Chinese.

Adult↗

Diamagnetic response of metallic photonic crystals at infrared and visible frequencies.

We show analytically and numerically that diamagnetic response (effective magnetic permeability mue<1) at infrared and visible frequencies can be achieved in photonic crystals composed of metallic nanowires or nanospheres when the wavelength is much larger than the lattice constant a (lambda approximately 2000a). When lambda approximately100a, the metallic photonic crystals will exhibit strong diamagnetic response (mue<0.8), leading to many interesting phenomena such as the unusual Brewster angle for s waves and incident-angle-and-polarization-independent reflection and transmission.

Journal Article↗

Time course of the antipsychotic effect and the underlying behavioral mechanisms.

Antipsychotic drugs work for patients only when given repeatedly. The overall temporal pattern of symptom improvement is not clear. Some recent data question the traditional 'delayed-onset' hypothesis and suggest that the onset of antipsychotic response may be relatively early, and the improvement may grow with repeated treatment. The present study systematically examined the time course of the antipsychotic effect and the underlying behavioral mechanisms using a conditioned avoidance response (CAR) model. Rats repeatedly treated with either typical (haloperidol) or atypical (olanzapine, risperidone) antipsychotics, but not anxiolytics (chlordiazepoxide), show an early-onset, progressive across-session decline in avoidance responding, which re-emerges when the treatment is stopped. This effect is dose-dependent, transferable between antipsychotics, and cannot be attributed to simple sedation or motor side effects. Furthermore, we found that the pattern of this drug-induced decline depends on the number of exposures to the conditioned stimulus in the presence of the drug, and is best understood as the result of drug-induced attenuation of the reinforcing effectiveness of the conditioned stimulus. We also found that repeated drug exposure can create a drug interoceptive state that allows the attenuated reinforcing property of the stimulus to be maintained over time. Together, these data provide preclinical support for the newly postulated 'early-onset' hypothesis, and suggest that the repeated antipsychotic CAR model may be useful for understanding the neurochemical and behavioral mechanisms underlying the clinical effects of antipsychotics in patients with schizophrenia.

Animals↗