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Biomedical subjects

L Zhao

Publications and source records attributed to L Zhao.

At least 37 records · Page 2Linked to original sources
PubMed2005

Antioxidant activity of gallic acid from rose flowers in senescence accelerated mice.

The activities of the antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx) in the blood and liver of the aging model induced by injection of different doses of D-gal into normal mice, and in senescence accelerated mice (SAM) of different ages, were determined. The results showed that the enzyme activities in the D-gal treated mice did not alter appreciably but the enzyme activities in blood of the SAM declined significantly with the increase in age, especially in the 9-month-old SAM. When gallic acid purified from rose flowers was used to treat the 9-month-old male SAM, it not only reinstated the activities of CAT and GPx but also significantly reduced the amount of malondialdehyde (MDA) in the liver, brain and kidney. The results demonstrated that 9-month-old male SAM represent an appropriate animal model to evaluate the antioxidant activities of natural products.

Aging↗
PubMed2005

Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation.

Aminoglycosides are commonly used antibiotics that often induce ototoxicity leading to permanent hair cell loss and hearing impairment. We hereby examined whether minocycline protects hair cells from gentamicin-induced hair cell damage. Two millimolar gentamicin significantly induced outer hair cell damage and the addition of minocycline to gentamicin-treated explants significantly increased hair cell survival in a dose-dependent manner. Additionally, we demonstrated that gentamicin induced p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation in these cells and these remarkable changes were blocked by minocycline treatments. Furthermore, we showed that the inhibitor of p38 MAPK or the inhibitor of caspase 3 only partially blocked gentamicin-induced hair cell damage, and the pretreatment of explants with the inhibitor of p38 MAPK and the inhibitor of caspase 3 together exerted a synergic protective effect against gentamicin-induced hair cell damage. Our results suggest that minocycline blocks gentamicin-induced hair cell loss possibly by inhibition of three mechanisms: p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation. This finding may explain why minocycline has protective activity in a variety of apoptotic models. Therapeutic intervention by using minocycline or related drugs may be a novel means for preventing inner ear injury following the use of aminoglycoside.

Animals↗
PubMed2005

17beta-estradiol induces Ca2+ influx, dendritic and nuclear Ca2+ rise and subsequent cyclic AMP response element-binding protein activation in hippocampal neurons: a potential initiation mechanism for estrogen neurotrophism.

Previous studies from our laboratory have shown that 17beta-estradiol (E2) promotes neurite outgrowth in hippocampal and cortical neurons. The neurotrophic effect of E2 seen in vitro has also been observed in vivo by other investigators who found that E2 enhances the density of dendritic spines involved in neuronal synaptic connection. To investigate the rapid upstream mechanisms initiating the E2 neurotrophic effect, we tested the hypothesis that E2 would directly activate Ca2+ influx in primary hippocampal neurons, which would result in activation of the transcription factor, cyclic AMP response element-binding protein (CREB), and regulate E2 enhancement of neurite outgrowth. Using fura-2 ratiometric and fluo-3 Ca2+ imaging, we demonstrated that E2 induced a significant rise in intracellular Ca2+ concentration ([Ca2+]i) through E2-induced Ca2+ influx. Interestingly, the rise in [Ca2+]i occurred not only in the cytoplasm, but also in the nucleus and dendrites of hippocampal neurons. Since CREB is activated by Ca2+-dependent kinases and is required for certain aspects of synaptic plasticity, we investigated whether E2 would lead to activation of CREB. Western immunoblotting and immunocytochemical analyses revealed that E2 induced rapid CREB activation consistent with rapid intracellular Ca2+ signaling, which was dependent on the influx of extracellular Ca2+. E2-induced increase in dendritic spine marker protein spinophilin was abolished following treatment with a small interfering RNA against CREB, indicating that E2-induced neurotrophic effect requires the upstream CREB activation. Results of these analyses indicate that E2-induced neurotrophic responses are mediated by a Ca2+ signaling cascade that is dependent upon extracellular Ca2+ and CREB activation. These data provide insights into the initiating mechanisms required to activate the estrogen neurotrophic response and provide a mechanistic framework for determining the neurotrophic efficacy of existing and emerging estrogen therapies for the brain.

Aniline Compounds↗
PubMed2005

Clinical investigation on coexisting of duodenal ulcer and gastric cancer in China.

The aim of this study was to investigate the prevalence of coexistent duodenal ulcer and gastric cancer in China, then to explore the features of clinical manifestations, endoscopy, pathology and possible pathogenesis. A retrospective analysis has been made on medical records in Remin Hospital, Wuhan University, Hubei Province, China from January 1991 to December 2002. 37 cases of coexistent duodenal ulcer and gastric cancer were found. 24.3% (9/37) had previous history of duodenal ulcer. 81.0% (30/37) of them lack alarm symptoms or signs and 87.1% (27/31) had alleviation in abdominal pain by acid inhibitor. Duodenal ulcer was single in all cases with seven in A1 stage, three in A2 stage, one in H1 stage, one in H2 stage, seven in S1 stage and 18 in S2 stage. 89.2% (33/37) of concurrent gastric cancer were in the corpus and antrum, with 78.1% (29/37) of them belonging to Bormann type II and 87.1% (27/37) being moderately differentiated adenocarcinoma. 83.7% of patients (31/37) had positive rapid urease test. The coexisting gastric cancer in patients with duodenal ulcer is infrequent but not rare. Gastroscopy screening and routine follow-up are necessary for patients with duodenal ulcer. Helicobacter pylori may be important pathogen for it. Helicobacter pylori eradication is recommended in patients with duodenal ulcer to reduce the risk of contaminant gastric cancer.

Aged↗
PubMed2005

Rose (Rosa rugosa)-flower extract increases the activities of antioxidant enzymes and their gene expression and reduces lipid peroxidation.

The effects of rose-flower extract on antioxidant enzymes were studied. The activities of catalase (CAT) and glutathione peroxidase (GPx) in 9-month-old senescence-accelerated mice (SAM mice) were lower than those in 6-month-old SAM mice. Therefore, 9-month-old SAM mice were the most appropriate targets for treatment with the rose-flower extract. The activities of CAT and GPx in SAM mice treated with rose-flower extract showed a marked increase in whole blood and liver. At the same time, the gene-expression level of CAT and GPx was upregulated in the liver, while malondialdehyde content in liver and brain decreased. Male SAM mice were more sensitive than female SAM mice. The mean and the longest lifespan of SAM mice were longer after treatment with rose-flower extract.

Aging↗
PubMed2005

Alterations in net glucose uptake and in the pancreatic B-cell GLUT2 transporter induced by diazoxide and by secretory stimuli.

The pancreatic B-cell GLUT2 transporter and glucose metabolism were examined in isolated rat islets subjected to treatments affecting insulin secretion. Diazoxide was used to inhibit, while glipizide or depolarization of the plasma membrane with a high extracellular K(+) concentration were used to stimulate insulin release in short-term experiments. Islet GLUT2 and insulin were determined by quantitative immunohistochemistry and GLUT2 was also determined by Western blot analysis. Islet net glucose uptake and glucose oxidation were measured using radioactively labelled glucose. Exposure of the islets to diazoxide was associated with a marked increase in the B-cell plasma membrane staining for GLUT2 and increased net glucose uptake. Glucose oxidation was not changed, which may reflect a lowered energy requirement. Conversely, islets subjected to a stimulated insulin secretion with glipizide or a high extracellular K(+) concentration showed a reduced staining of the GLUT2 transporter. The net glucose uptake and glucose oxidation were also reduced. In islets exposed to the high K(+) concentration no change in the molecular weight or phosphorylation of GLUT2 was observed but a lesser amount of the transporter was found by Western blot analysis. Thus, GLUT2 and glucose uptake in the pancreatic B-cell are modified by the secretory process, which suggests that changes in the glucose transporter have a functional role in normal B-cell physiology.

Animals↗
PubMed2004

Computer-identified nuclear localization signal in exon 1A of the transporter DMT1 is essentially ineffective in nuclear targeting.

Divalent metal transporter 1 (DMT1; also called DCT1, Nramp2, or SLC11A2) has multiple isoforms that localize differently in many cell types. DMT1 +IRE species (encoded by mRNA with an iron-responsive element) are limited to the plasma membrane and cytosolic vesicles. In neural cells, -IRE isoforms of DMT1 (encoded by mRNA lacking an IRE) localize to the nucleus, plasma membrane, and cytosolic vesicles. In considering nuclear compartmentalization of -IRE isoforms, we hypothesized that the newly identified exon 1A in the N-terminus of this transporter might contain a nuclear localization signal. DNA constructs starting with exon 1A and ending with exons encoding alternative isoforms were made and transiently transfected into HEK293T and PC12 cells as well as rat sympathetic neurons. None of the constructs appeared in the nucleus despite the presence of exon 1A. Antibody specific for exon 1A was also used in both immunostaining and Western blots to investigate localization of exon 1A expressed both endogenously and ectopically in cells. Again, nuclear localization of DMT1 containing exon 1A was not observed. Our data suggest that exon 1A is neither sufficient nor necessary for DMT1 to appear in the nucleus.

Animals↗
PubMed2004

Quantum magneto-oscillations in a supramolecular Mn(II)-[3 x 3] grid.

The magnetic grid molecule Mn(II)-[3 x 3] has been studied by high-field torque magnetometry at 3He temperatures. At fields above 5 T, the torque versus field curves exhibit an unprecedented oscillatory behavior. A model is proposed which describes these magneto-oscillations well.

Journal Article↗
PubMed2004

Anti-apoptotic activity of the glutathione peroxidase homologue encoded by HIV-1.

The third reading frame of the envelope gene from HIV-1 codes for a protein homologous to the human selenoprotein glutathione peroxidase (GPX). Cells stably or transiently transfected with a HIV-1 GPX construct are protected against the loss of the mitochondrial transmembrane potential and subsequent cell death induced by exogenous reactive oxygen species (ROS) as well as mitochondrion-generated ROS. However, HIV-1 GPX does not confer a general apoptosis resistance, because HIV-1 GPX-transfected cells were not protected against cell death induced by staurosporine or oligomycin. The inhibition of cell death induced by the ROS donor tert-butylhydroperoxide was also observed in cells depleted from endogenous glutathione (GSH), suggesting that GSH is not the sole electron acceptor for HIV-1 GPX. Clinical HIV-1 isolates from long-term non-progressors (untreated patients with diagnosed HIV-1 infection for > 10 years, with CD4 T cell count of > 500 cells/mm3) mostly possess an intact GPX gene (with only 18% of loss-of-function mutations), while HIV-1 isolates from patients developing AIDS contain non-functional GPX mutants in 9 out of 17 cases (53%). Altogether, these data suggest that HIV-1 GPX possesses a cytoprotective, pathophysiologically relevant function.

Amino Acid Sequence↗
PubMed2004

Interrelationship between methionine and cystine of early Peking ducklings.

A 4 x 5 factorial experiment containing 4 cystine levels (0.325, 0.406, 0.487, or 0.568%) and 5 methionine levels (0.285, 0.385, 0.485, 0.585, or 0.685%) was conducted to evaluate the interrelationship between methionine and cystine in corn-peanut meal diet for Peking ducklings from hatch to 21 d of age. Eight hundred 1-d-old male white Peking ducklings were assigned to 20 experimental treatments. All treatments were replicated 4 times using 10 ducklings per pen. As dietary methionine level increased, weight gain and feed intake increased and then decreased; the quadratic response of weight gain was significant (P < 0.05). The methionine requirement for maximum efficiency of feed utilization (0.585%) was higher than for maximum weight gain (0.485%). According to the quadratic model, the optimal methionine requirement of Peking ducklings from hatch to 21 d of age was 0.481% (95% of the level at maximum response). The plasma uric acid concentration was very low (P < 0.05) when dietary methionine was 0.485%. When dietary methionine was excessive (0.685%), the plasma homocysteine concentration increased (P < 0.05). On the other hand, the cystine requirement of ducklings from hatch to 21 d of age was not more than 0.325%. A high level of cystine (0.568%) depressed weight gain and feed intake (P < 0.05), but cystine supplementation in the diets lowered the plasma homocysteine concentration (P < 0.05). There were no significant interactions between methionine and cystine on growth performance, plasma uric acid, and plasma homocysteine.

Animal Feed↗
PubMed2004

A gallic acid derivative and polysaccharides with antioxidative activity from rose (Rosa rugosa) flowers.

In this study, the major antioxidant components of rose flower were identified. An aqueous extract of rose flowers was chromatographed on CM-cellulose in ammonium acetate buffer (10 mM, pH 4.5) to yield three un-adsorbed peaks F1, F2 and F3. Each of these peaks was subjected to gel filtration on Sephadex G75. F1 yielded two peaks, whereas both F2 and F3 gave rise to only a single peak. Spectroscopic studies using NMR and FTIR revealed that F3 is a gallic acid derivative. It exhibited the highest antioxidative potency. F1-a derived from F1 by gel filtration is mainly a polysaccharide-peptide complex with less potent antioxidative activity. F2 is a polysaccharide also with reduced antioxidant activity. This study demonstrates, for the first time, the presence of both gallic acid derivatives and polysaccharides as major antioxidant principles of the aqueous extract of rose flowers.

Animals↗
PubMed2004

Association of habitual long-distance running with the thickness of skeletal muscles and subcutaneous fat in the body extremities and trunk in middle-aged men.

AIM: We investigated the association of habitual long-distance running with the thickness of skeletal muscles and subcutaneous fat in the body extremities and trunk in middle-aged men using ultrasonography. METHODS: Three groups of healthy middle-aged men [mean (SD), 62.1 (2.8) years] took part in this investigation: a high-level group of 11 master runners who had competed in a 42.195 km race and run 51.6 (21.7) km every week, an intermediary-level group of 10 master runners who had competed in a 5-20 km race and run 9.3 (4.9) km every week, and a low-level group of 7 untrained men who continued to do no systematic training. The muscle thickness at 8 sites and the subcutaneous fat thickness at 10 sites were measured by B-mode ultrasonography, and were compared among the 3 groups. RESULTS: The high-level group had 10.0(-1)5.2% higher values for muscle thickness at the erector spinae, hamstrings, tibialis anterior, and triceps surae, compared with the intermediary-level and the low-level groups (p<0.05-0.001). The thickness of the subcutaneous fat about the rectus abdominis and external oblique was lower in the high-level group than in the intermediary-level and the low-level groups (p<0.05). CONCLUSIONS: Middle-aged male master athletes who habitually run at a high level have more muscle thickness in the lower extremities and trunk, and less subcutaneous fat thickness in the central regions of the body than do middle-aged men who habitually run at an intermediary level or do not run at all.

Abdominal Muscles↗
PubMed2003

Mutational analysis of roles for extracellular cysteine residues in the assembly and function of human alpha 7-nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChR) containing alpha7 subunits self-assemble into simple, homopentameric complexes. However, successful heterologous expression of functional alpha7-nAChR has only been achieved in a few host cell types, such as the SH-EP1 human epithelial cell line. All ionotropic glycine receptor, GABA(A) receptor, 5-HT(3) receptor, and nAChR subunits contain a pair of highly conserved cysteine residues (C150 and C164 for alpha7 subunits) in their N-terminal extracellular domain. These residues are thought to be involved in the formation of a conserved cystine loop that is critical to the proper folding and assembly of subunits. However, nAChR alpha7 (and alpha8) subunits also contain a third cysteine residue, C138, N-terminal to the conserved cysteine pair. Using SH-EP1 cells as a host for heterologous expression, we evaluated the roles of C138, C150, and C164 in subunit folding, assembly, and cell surface expression and function of alpha7-nAChR. Results indicate that mutation of C138, but not of C150 or C164, yields an nAChR that can assemble to form (125)I-labeled alpha-bungarotoxin binding sites expressed on the cell surface. Further, whole-cell patch clamp recordings demonstrate that mutation of C138 to alanine does not alter the function of the fully assembled alpha7-nAChR. These results indicate that C150 and C164 are required for surface expression, but that C138 is neither necessary for nor inhibitory toward the surface expression and function of human alpha7-nAChR. These results suggest that disulfide bond formation between C138 and either C150 or C164, if it occurs, has no significant effect on alpha7-nAChR assembly or function.

Alanine↗
PubMed2003

INTERMAP: the dietary data--process and quality control.

The aim of this report is to describe INTERMAP standardized procedures for assessing dietary intake of 4680 individuals from 17 population samples in China, Japan, UK and USA: Based on a common Protocol and Manuals of Operations, standardized collection by centrally trained certified staff of four 24 h dietary recalls, two timed 24-h urines, two 7-day histories of daily alcohol intake per participant; tape recording of all dietary interviews, and use of multiple methods for ongoing quality control of dietary data collection and processing (local, national, and international); one central laboratory for urine analyses; review, update, expansion of available databases for four countries to produce comparable data on 76 nutrients for all reported foods; use of these databases at international coordinating centres to compute nutrient composition. Chinese participants reported 2257 foods; Japanese, 2931; and UK, 3963. In US, use was made of 17,000 food items in the online automated Nutrition Data System. Average time/recall ranged from 22 min for China to 31 min for UK. Among indicators of dietary data quality, coding error rates (from recoding 10% random samples of recalls) were 2.3% for China, 1.4% for Japan, and UK; an analogous US procedure (re-entry of recalls into computer from tape recordings) also yielded low discrepancy rates. Average scores on assessment of taped dietary interviews were high, 40.4 (Japan) to 45.3 (China) (highest possible score: 48); correlations between urinary and dietary nutrient values--similar for men and women--were, for all 4680 participants, 0.51 for total protein, range across countries 0.40-0.52; 0.55 for potassium, range 0.30-0.58; 0.42 for sodium, range 0.33-0.46. The updated dietary databases are valuable international resources. Dietary quality control procedures yielded data generally indicative of high quality performance in the four countries. These procedures were time consuming. Ongoing recoding of random samples of recalls is deemed essential. Use of tape recorded dietary interviews contributed to quality control, despite feasibility problems, deemed remediable by protocol modification. For quality assessment, use of correlation data on dietary and urinary nutrient values yielded meaningful findings, including evidence of special difficulties in assessing sodium intake by dietary methods.

Adult↗
PubMed2003

Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study.

The purpose of the study was to compare nutrient intakes among Chinese, Japanese, UK, and US INTERMAP samples, and assess possible relationships of dietary patterns to differential patterns of cardiovascular diseases between East Asian and Western countries. Based on a common Protocol and Manuals of Operations, high-quality dietary data were collected by four standardized 24-h dietary recalls and two 24-h urine collections from 17 population samples in China (three samples), Japan (four samples), UK (two samples), and USA (eight samples). There were about 260 men and women aged 40-59 years per sample--total N=4680. Quality of dietary interview and data entry were monitored and enhanced by extensive systematic ongoing quality control procedures at local, country, and international level. Four databases on nutrient composition of foods from the four countries were updated and enhanced (76 nutrients for all four countries) by the Nutrition Coordinating Center, University of Minnesota, in cooperation with Country Nutritionists. The mean body mass index was much higher for Western than East Asian samples. Macronutrient intakes differed markedly across these samples, with Western diet higher in total fat, saturated and trans fatty acids, and Keys dietary lipid score, lower in total carbohydrate and starch, higher in sugars. Based on extensive published data, it is a reasonable inference that this pattern relates to higher average levels of serum total cholesterol and higher mortality from coronary heart disease in Western than East Asian populations. The rural Chinese diet was lower in protein, especially animal protein, in calcium, phosphorus, selenium, and vitamin A. Dietary sodium was higher, potassium lower, hence Na/K ratio was higher in the Asian diet, especially for Chinese samples. This pattern is known to relate to risks of adverse blood pressure level and stroke. At the end of the 20th century, East Asian and Western diets remain significantly different in macro- and micronutrient composition. Both dietary patterns have aspects that can be regarded, respectively, as adverse and protective in relation to the major adult cardiovascular diseases. In both Asian and Western countries, public efforts should be targeted at overcoming adverse aspects and maintaining protective patterns for prevention and control of cardiovascular diseases.

Adult↗
PubMed2003

Computer simulation of Clostridium botulinum strain 56A behavior at low spore concentrations.

It is generally assumed that spore behavior is independent of spore concentration, but recently published mathematical models indicate that this is not the case. A Monte Carlo simulation was employed in this study to further examine the independence assumption by evaluating the inherent variance in spore germination data. All simulations were carried out with @Risk software. A total of 500 to 4,000 iterations were needed for each simulation to reach convergence. Lag time and doubling time from a higher inoculum concentration were used to simulate the time to detection (TTD) at a lower inoculum concentration under otherwise identical environmental conditions. The point summaries of the simulated and observed TTDs were recorded for the 26 simulations, with kinetic data at the target inoculum concentration. The ratios of the median (R(m) = median(obs)/median(sim)) and 90% range (R(r) = 90% range(obs)/90% range(sim)) were calculated. Most R(m) and R(r) values were greater than one, indicating that the simulated TTDs were smaller and more homogeneous than the observed ones. R(r) values departed farther from one than R(m) values. Ratios obtained when simulating 1 spore with 10,000 spores deviated the farthest from one. Neither ratio was significantly different from the other when simulating 1 spore with 100 spores or simulating 100 spores with 10,000 spores. When kinetic data were not available, the percent positive observed at the 95th percentile of the simulated TTDs was obtained. These simulation results confirmed that the assumption of independence between spores is not valid.

Clostridium botulinum↗
PubMed2002

Time-to-detection, percent-growth-positive and maximum growth rate models for Clostridium botulinum 56A at multiple temperatures.

We previously developed models for the influence of inoculum size on the growth kinetics (time-to-detection and maximum growth rate) and percent-growth-positive samples of Clostridium botulinum 56A with factors of inoculum size (1, 100, and 10,000 spores/sample). pH (5.5. 6.0 and 6.5) and sodium chloride concentration (0.5%, 2% and 4%) at 30 degrees C. In this present study, data were collected at two more temperatures (15 and 22 degrees C), making the final design a complete 3 X 3 X 3 X 3 factorial with a total of 81 conditions. Growth was followed hourly as change in A620. The Gompertz equation was fit to the growth data, and the parameters derived were used to calculate the maximum growth rate and time-to-detection. Linear regression with polynomial terms was used to analyze the effect of environmental factors on time-to-detection and maximum growth rate. Logistic regression with polynomial terms was used to analyze the data for percent-growth-positive. Despite the fact that the variance is larger in this extended data set (which includes two temperatures that are further away from the optimum), the inoculum size effect is clearly demonstrated. When inoculum size increased, the percent-growth-positive samples increased and the time-to-detection decreased. When the inoculum was 1000 spores/sample or higher, little additional effect on time-to-detection was observed. Inoculum size might influence results through simple probability or quorum sensing. Our results show that the observed effect of inoculum size from the previous report at a single temperature is not restricted to a specific growth condition, but rather a general phenomenon. The maximum growth rate was independent of inoculum levels, confirming our previous results.

Clostridium botulinum↗