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Biomedical subjects

Y Li

Publications and source records attributed to Y Li.

At least 163 records · Page 9Linked to original sources

[Autonomic nervous system involvement in chronic inflammatory demyelinating polyneuropathy].

INTRODUCTION: Involvement of the autonomic nervous system during Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is rare. Localised hyperhydrosis and Claude Bernard Horner (CBH) syndrome have never been reported in patients with CIDP. CASE REPORT: We report the case of a 65-year-old right handed man who presented with hyperhydrosis localised to the right hemithorax and hemiface and a left CBH syndrome. After an extensive workup, the patient was found to have CIDP as the only cause of autonomic nervous system involvement. The symptoms resolved slowly after three courses of intravenous immunoglobulins. CONCLUSION: Signs of autonomic nervous system involvement can be observed in CIDP as in Guillain-Barré syndrome. This case report shows that immunomodulatory treatment can be effective against dysautonomia in CIDP.

Aged↗

siRNA targeting the leader sequence of SARS-CoV inhibits virus replication.

SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.

5' Untranslated Regions↗

A novel DNA vaccine based on ubiquitin-proteasome pathway targeting 'self'-antigens expressed in melanoma/melanocyte.

Cancer vaccine that targets 'self'-antigens expressed at high levels in tumor cells is a potentially useful immunotherapy, but immunological tolerance often defeats this strategy. Here, we describe the use of a naked DNA vaccine encoding a self tumor antigen, tyrosinase-related protein 2, to whose N-terminus ubiquitin is fused in a 'nonremovable' fashion. Unlike conventional DNA vaccines, this vaccine broke the tolerance and induced protective immunity to melanoma in C57BL/6 mice, as evaluated by tumor growth, survival rate and lung metastasis. The protective immunity was cancelled in the proteasome activator PA28alpha/beta knockout mice. Moreover, this vaccination exhibited therapeutic effects on melanoma implanted before vaccination. Our findings provide evidence for the first time that naked DNA vaccines encoding a ubiquitin-fused self-antigen preferentially induce the main effector CD8+ T cells through efficient proteolysis mediated by the ubiquitin-proteasome pathway, and lead the way to strategies aimed at targeting tissue differentiation antigens expressed by tumors.

Animals↗

Effects of perceived peer isolation and social support availability on the relationship between body mass index and depressive symptoms.

OBJECTIVE: To examine relationships between body mass index (BMI) and psychological correlates in Chinese school adolescents during the period of economic transition. DESIGN: Baseline data of 1655 Chinese adolescents aged 11-15 y were retrieved from a longitudinal smoking cessation and health promotion program in Wuhan, China. Assessments of body weight and height, depressive symptoms, perceived peer isolation (PPI) and perceived availability of social support (PASS) were collected. RESULTS: Based on the International Obesity Task Force (IOTF) age-and sex-specific BMI cutoffs, 12.5% of boys and 9.2% of girls were overweight. In girls, high BMI was significantly related to higher self-reported depressive symptoms, and was dominantly mediated by PPI. On the contrary, high BMI boys reported significantly lower levels of PPI although high PPI level aggravated depressive symptoms. For both girls and boys, the observed effect of PPI on the relationship between BMI and depressive symptoms was sustained only in low PASS boys and girls. CONCLUSIONS: The present study revealed different effects of PPI on the association of BMI and depressive symptoms between boys and girls, which were buffered by levels of PASS. The findings of this study may contribute to our understanding of the influences of psychological correlates in pediatric overweight in the Eastern cultural environment.

Adolescent↗

Gender-specific association between pulse pressure and C-reactive protein in a Chinese population.

There is growing evidence that low-grade chronic inflammation, as reflected by the raised serum concentration of C-reactive protein, might be a risk factor for hypertension, in particular in women. We therefore investigated gender-specific associations of systolic and diastolic blood pressure and pulse pressure with serum C-reactive protein concentration in a Chinese population sample. In 463 participants, we measured serum C-reactive protein concentration using a high-sensitivity immunonephelometric latex-enhanced assay. We performed single and multiple linear regression analyses. The 224 male and 239 female subjects were of similar age (51.0 years) and had similar levels of systolic blood pressure (124.7 mmHg) and pulse pressure (47.1 mmHg), but men, compared with women, had higher diastolic blood pressure (79.6 vs 75.8 mmHg; P<0.0001) and body mass index (24.3 vs 23.4 kg/m2; P=0.003). Both before and after adjustment for age, age2, body mass index, current smoking, alcohol intake, and use of antihypertensive drugs, pulse pressure was significantly associated with serum C-reactive protein concentration in women (P< or =0.002) but not in men (P>0.10; P=0.02 for interaction between gender and serum C-reactive protein). In women, with one-fold increase in serum C-reactive protein concentration, pulse pressure was 1.94 mmHg higher. The categorical analyses confirmed our findings. With similar adjustments applied, women in the fourth quartile, compared with those in the lowest quartile, had a 7.6 mmHg higher pulse pressure (95% confidence interval 3.5-11.7 mmHg; P=0.0003). Furthermore, when women were analysed according to menopausal status, the association between pulse pressure and C-reactive protein was only significant in postmenopausal (P< or =0.04), but not in premenopausal, subjects (P> or =0.21). In conclusion, taken together with the previous gender-specific observations on carotid lesions and hypertension, our finding suggests that chronic low-grade inflammation might play a role in the widening of pulse pressure in Chinese women. This cross-sectional observation warrants further investigation in prospective studies.

Biomarkers↗

Cell-based selection of internalizing fully human antagonistic antibodies directed against FLT3 for suppression of leukemia cell growth.

FMS-like tyrosine kinase 3 (FLT3) receptor is highly expressed in an array of hematological malignancies including approximately 90% of acute myelogenous leukemia (AML). Ligand stimulation of the receptor promotes the survival and proliferation of leukemia cells. Strategies targeting FLT3 using monoclonal antibodies may therefore constitute an effective therapeutic approach for these leukemia. Towards this, we selected a naïve antibody phage display library on both recombinant FLT3 receptor protein and FLT3-expressing leukemia cells using a tailored selection scheme that was designed to isolate antagonistic phage antibodies that not only interfere with receptor/ligand binding but also trigger receptor internalization upon cell surface binding. Phage antibodies were screened first for their ability to bind to cell surface receptor and induce receptor internalization, followed by their activity in blocking ligand-receptor interaction and neutralizing ligand-stimulated receptor activation and cell proliferation. We identified three fully human antibodies, EB10, A2IN, and D4-3, which bound specifically to both soluble and cell surface-expressed FLT3. All three antibodies were shown to be internalized upon binding to cell surface-expressed receptor in a time-dependent fashion. EB10 and D4-3 blocked ligand binding to the receptor with IC(50)s of 14 and 7 nM, respectively. Further, EB10 and D4-3 inhibited FLT3 ligand-induced receptor phosphorylation and cell proliferation in EOL-1 leukemia cells. Taken together, these results suggest that both EB10 and D4-3 may represent excellent therapeutic candidates for the treatment of FLT3-expressing human leukemia, both as unmodified antibodies and as conjugates of cytotoxic agents.

Antibodies, Monoclonal↗

Arf family GTPases: roles in membrane traffic and microtubule dynamics.

Database mining and phylogenetic analysis of the Arf (ADP-ribosylation factor) superfamily revealed the presence in mammals of at least 22 members, including the six Arfs, two Sars and 14 Arl (Arf-like) proteins. At least six Arf family members were found in very early eukaryotes, including orthologues of Arf, Sar, Arl2, Arl3, Arl6 and Arl8. While roles for Arfs in membrane traffic are well known, those for most of the Arls remain unknown. Depletion in cells of the most closely related human Arf proteins, Arf1-Arf5, reveals specificities among their cellular roles and suggests that they may function in pairs at different steps in endocytic and secretory membrane traffic. In addition, recent results from a number of laboratories suggest that several of the Arl proteins may be involved in different aspects of microtubule-dependent functions. Thus, a second major role for Arf family GTPases, that of regulating microtubules, is emerging. Because membrane traffic is often dependent upon movement of vesicles along microtubules this raises the possibility that these two fundamental functions of Arf family members, regulation of vesicle traffic and microtubule dynamics, diverged from one function of Arfs in the earliest cells that has continued to branch and allow additional levels of regulation.

ADP-Ribosylation Factors↗

Preparation, characterization and in vitro release properties of ibuprofen-loaded microspheres based on polylactide, poly(epsilon-caprolactone) and their copolymers.

In this paper, ibuprofen was encapsulated into microspheres by oil-in-water (o/w) emulsion solvent evaporation method. Biodegradable polymers with certain compositions and characteristics such as polylactide (PLA), poly(epsilon-caprolactone) (PCL) and their block copolymer were used to prepare the microspheres. The results indicate that, under the same processing conditions, the drug entrapment efficiency was similar (approximately 80%) for microspheres prepared with PLA and P(LA-b-CL) (78.7/21.3 by mole), but it was only 25.4% for PCL microspheres. The in vitro drug release rate decreased in the order of PCL, P(LA-b-CL) (78.7/21.3 by mole) and PLA microspheres. PCL microspheres showed more serious burst release during the first day (almost 80%) than P(LA-b-CL) (50%) and PLA microspheres (18%). The complete ibuprofen release duration from the last two kinds of microspheres exceeded 1 month. Characterization of the microspheres by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and polarized optical microscope (POM) revealed that ibuprofen was amorphous in PCL microspheres and partially crystalline in P(LA-b-CL) and PLA microspheres. The different release behaviour of ibuprofen from the three kinds of microspheres could be attributed to the different crystallinity of the studied polymers and drug dispersion state in polymer matrices. All the above results suggest that the copolymer with a certain ratio of lactide to -caprolactone could have potential applications for long-term ibuprofen release.

Absorption↗

Current ideas about applications of heat shock proteins in vaccine design and immunotherapy.

Heat shock proteins (HSPs), as molecular chaperones, perform critical functions in maintaining cell homeostasis. Certain HSPs in extra-cellular milieu are capable of modulating innate and adaptive immunity due to their ability to chaperone polypeptides and to interact with the host's immune system, particularly professional antigen presenting cells (APCs). This review summarizes the immunomodulating functions of HSPs and their potential applications in cancer immunotherapy.

Animals↗

Radioprotection by fullerenols of Stylonychia mytilus exposed to gamma-rays.

The aim was to study the protective effects of fullerenols, C60(OH)x, on Stylonychia mytilus cells exposed to 60Co gamma-rays and the probable mechanisms of fullerenols protection. Ciliated protozoans Smytilus, kept in solutions of fullerenols at different concentrations, were irradiated with 60Co gamma-rays to various dose levels. Surviving cells were counted each day over 5 days after irradiation, and the surviving fraction was calculated. The relations of the surviving fraction to radiation dose and to fullerenols concentration were studied. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and lipofusion (LIP) levels in S. mytilus were also measured. The surviving fraction of S. mytilus decreased with increasing gamma-ray doses from 100 to 2000 Gy. Fullerenols enhanced the surviving fraction, except for the highest gamma-ray dose level. The maximum protection by fullernols occurred at a concentration of 0.10 mg ml(-1). However, fullerenols at concentration of 0.25 mg ml(-1) yielded a surviving fraction lower than that for the control sample. Fullerenols at a concentration of 0.10 mg ml(-1) increased the SOD and CAT activities in the gamma-ray plus fullerenols (gamma + F) group compared with the levels in both the gamma-ray (gamma) group (p < 0.01) and the control group (p < 0.01). The MDA and LIP levels in the gamma + F groups (p < 0.01) were significantly lower than that in both the control group (p < 0.05) and the gamma group (p < 0.01). At a concentration of 0.25 mg ml(-1), fullerenols reduced the SOD and CAT activities, but increased the MDA and LIP level compared with the control. There was no significant difference in SOD and CAT activities between the gamma + F group and gamma group. While the MDA and LIP level in the gamma + F and gamma groups were similar at a dose of 500 Gy, the LIP level in the gamma + F group was significantly higher than that in the gamma group (p < 0.01) at a dose of 2000 Gy. Fullerenols are good radiation protectors for the protozoan S. mytilus exposed to gamma-rays. The effectiveness of radioprotection depends on both fullerenols concentration and gamma-ray dose. The protective effect of fullerenols on damage induced by gamma-rays seems to be mediated, at least in part, through their anti-oxidative and radical scavenging activities.

Animals↗

A new dicoumarinoid glycoside from Daphne giraldii.

A new dicoumarinoid glycoside, named giraldoid A (1), has been isolated from Daphne giraldii Nitsche. The structure of 1 was determined as 7-O-beta-glucosyl-8-(7-hydroxy-2H-1-benzopyran-2-one-8-)yl-2H-1-benzopyran-2-one on the basis of chemical reactions and spectroscopic methods.

China↗

Predictive model for the survival, death, and growth of Salmonella typhimurium in broiler hatchery.

Contamination and penetration of salmonellae into hatching eggs may comprise an important link in the transmission of these bacteria to growing birds, processed carcasses, and eventually to the consumer. In this study, a predictive model for Salmonella typhimurium as a function of initial cell number and storage or incubation time at a nearly constant temperature and humidity was developed and evaluated to compute the bacterial load after 1 d (holding), 10 d (candling), 17 d (incubation), and 21 d (chick processing). Experiments were conducted for S. typhimurium with both high initial bacterial load (HIBL) and low initial bacterial load (LIBL) of 6.0 and 3.5 log cfu/egg, respectively. Eggs with HIBL experienced 2.0 log reduction in the bacterial load after holding at 4 degrees C for 24 h and 3.0 log increase in the bacterial load during incubation and hatch at approximately 37 degrees C between 17 d and 21 d. Experimental data showed that bacterial load of S. typhimurium from holding to chick processing changed from 3.7 to 6.6 log cfu/egg and from 3.7 to 2.7 log cfu/egg in HIBL and LIBL eggs, respectively. The developed model was able to predict bacterial load of S. typhimurium from 3.6 to 6.6 log cfu/egg in HIBL eggs and from 3.4 to 2.7 log cfu/egg in LIBL eggs from holding to chick processing. Root mean square errors and plot of predicted compared with observed bacterial load of S. typhimurium in contaminated eggs yielded a good fit and prediction. The predicted and experimental results indicated that incubated broiler eggs have an increase in internal bacterial loads between incubation and hatch. This model can be used as a tool to predict bacterial load of S. typhimurium in contaminated eggs as well as help predict the behavior of S. typhimurium during hatch.

Animal Husbandry↗

SNP analysis of AMY2 and CTSL genes in Litopenaeus vannamei and Penaeus monodon shrimp.

Genetic studies in shrimp have focused on disease, with production traits such as growth left unexamined. Two shrimp species, Litopenaeus vannamei and Penaeus monodon, which represent the majority of US shrimp imports, were selected for single nucleotide polymorphism (SNP) discovery in alpha-amylase (AMY2) and cathepsin-l (CTSL), both candidate genes for growth. In L. vannamei, four SNPs were found in AMY2 and one SNP was found in CTSL. In P. monodon, one SNP was identified in CTSL. The CTSL gene was mapped to linkage group 28 of P. monodon using the female map developed with the Australian P. monodon mapping population. Association analyses for the AMY2 and CTSL genes with body weight (BW) were performed in two L. vannamei populations. While neither gene was found to be significantly associated with BW in these populations, there was a trend in one population towards higher BW for allele G of CTSL SNP C681G.

Animals↗

High level expression of a recombinant acid phytase gene in Pichia pastoris.

AIMS: To achieve high phytase yield with improved enzymatic activity in Pichia pastoris. METHODS AND RESULTS: The 1347-bp phytase gene of Aspergillus niger SK-57 was synthesized using a successive polymerase chain reaction and was altered by deleting intronic sequences, optimizing codon usage and replacing its original signal sequence with a synthetic signal peptide (designated MF4I) that is a codon-modified Saccharomyces cerevisiae mating factor alpha-prepro-leader sequence. The gene constructs containing wild type or modified phytase gene coding sequences under the control of the highly-inducible alcohol oxidase gene promoter with the MF4I- or wild type alpha-signal sequence were used to transform Pichia pastoris. The P. pastoris strain that expressed the modified phytase gene (phyA-sh) with MF4I sequence produced 6.1 g purified phytase per litre of culture fluid, with the phytase activity of 865 U ml(-1). The expressed phytase varied in size (64, 67, 87, 110 and 120 kDa), but could be deglycosylated to produce a homogeneous 64 kDa protein. The recombinant phytase had two pH optima (pH 2.5 and pH 5.5) and an optimum temperature of 60 degrees C. CONCLUSIONS: The P. pastoris strain with the genetically engineered phytase gene produced 6.1 g l(-1) of phytase or 865 U ml(-1) phytase activity, a 14.5-fold increase compared with the P. pastoris strain with the wild type phytase gene. SIGNIFICANCE AND IMPACT OF THE STUDY: The P. pastoris strain expressing the modified phytase gene with the MF4I signal peptide showed great potential as a commercial phytase production system.

6-Phytase↗

Partial molecular characterization, polymorphism and chromosomal localization of the porcine PSMD4 gene.

The complete coding sequence of porcine PSMD4 gene encoding proteasome 26S non-ATPase subunit 4 was obtained by the reverse transcriptase-polymerase chain reaction (RT-PCR) and deposited in GenBank nucleotide database (AY704418). The nucleotide sequence and the predicted protein sequence shared the high sequence identity with their mammalian counterparts. A G/A single nucleotide polymorphism in intron 9 detected as Hin6I PCR-restriction fragment length polymorphism (PCR-RFLP) shows allele frequency differences between Meishan, Erhualian, Tibetan, Large White and Duroc breeds. Analyses of somatic cell hybrid panel (SCHP) and radiation hybrid (IMpRH) panel revealed that PSMD4 gene maps to SSC 4q21-q23 and closely linked the SW512 (14 cR, LOD = 19.47).

Amino Acid Sequence↗

The association of smoking and subclinical atherosclerosis in Type 2 diabetes: modification by duration of diabetes.

BACKGROUND: Diabetes is a relatively common disease in the United States, and cardiovascular disease is the major cause of morbidity and mortality among persons with diabetes. While smoking is one of the most well-established risk factors for heart disease and atherosclerosis, the effect of smoking on atherosclerosis among diabetic patients has not been thoroughly investigated. The primary objective of this paper was to evaluate the impact of smoking on atherosclerosis among Type 2 diabetic patients and to evaluate whether smoking associations with atherosclerosis are modified by diabetes-related variables. METHODS: We used cross-sectional baseline data from a randomized controlled trial to evaluate the associations between smoking and common carotid artery intima-media thickness (IMT) in 299 subjects with Type 2 diabetes. There were 34 (11%) current cigarette smokers, 73 (24%) former cigarette smokers, and 192 (64%) subjects who had never smoked regularly. RESULTS: There was an increasing trend in mean carotid IMT with both longer duration and increased frequency of smoking (adjusted P for trend 0.04 and 0.02, respectively). The mean +/- SE carotid IMT was non-significantly thicker (0.872 +/- 0.01 mm) in diabetic patients who had ever smoked than never smokers (0.842 +/- 0.01 mm) after controlling for age, gender and other potential confounders (P = 0.08). The negative effects of ever smoking (P = 0.01 for interaction), number of cigarettes smoked daily (P = 0.003 for interaction) and duration of smoking (P = 0.03 for interaction) on carotid IMT were accentuated with longer duration of diabetes. CONCLUSION: Smoking is associated with subclinical atherosclerosis in diabetic persons and interacts with duration of diabetes to accentuate atherosclerosis. The association between carotid IMT and duration of diabetes increases with both the frequency and duration of smoking.

Adult↗

Enhanced intracellular glutathione synthesis and excretion capability of Candida utilis by using a low pH-stress strategy.

AIMS: To study the effect of low pH stress on glutathione (GSH) synthesis and excretion capability of GSH fermentation production in Candida utilis. METHODS AND RESULTS: When C. utilis WSH 02-08 was cultivated in a glucose-ammonium sulfate medium without pH control, GSH leakage occurred when the pH of the medium decreased to 1.5. However, analysis of the cell viability indicated that the cells were not lysed. To further study the effect of low pH stress on GSH production, pH-controlled batch cultures were conducted, where the pH was switched from 5.5 to 1.2 at 24 h and maintained at 1.2 for 6 h. Nearly all intracellular GSH was leaked into the medium and the cell viability decreased dramatically, conceiving a long-term exposure of strain WSH 02-08 at low pH environment led to a complete cell lysis. A critical point (treated at pH 1.2 for 3 h) was experimentally determined, where most cells were alive but suffering a low pH stress. Low pH-stressed C. utilis cells displayed an increased intracellular GSH synthesis and export capability, which protected the cells against short-term low pH treatment. CONCLUSIONS: Using this knowledge, a low pH-stress strategy was developed and applied in fed-batch production of GSH and 197.3 mg l-1 of GSH was secreted into the medium. The GSH-specific production yield could be increased from 2.11 to 2.67% (w/w), and the total GSH concentration could reach 737.1 mg l-1 and increased by 24.9%. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of GSH secretion of C. utilis at low pH. This study demonstrated the importance of the physiology-based fermentation strategy in the production of useful metabolites.

Candida↗