Biomedical subjects

Li Zhu

Publications and source records attributed to Li Zhu.

At least 73 records · Page 4Linked to original sources

PubMed2005

Polypeptide from Chlamys farreri inhibits murine thymocytes apoptosis and modulates UVB induced signaling pathway activation.

Polypeptide from Chlamys farreri (PCF) has been identified as a potent antioxidant and photoprotective agent. In this study, we investigated whether PCF could inhibit apoptosis of murine thymocytes induced by ultraviolet B (UVB) and modulate UVB induced the mitogen-activated protein kinases (MAPKs) cascade in vitro. Our results show that PCF inhibit UVB-induced apoptotic cell death in murine thymocytes. We also found that PCF potently stimulated the phosphorylation of ERKs, which is involved in the cell survival-signaling cascade. Furthermore, the specific inhibition of the ERKs pathways by PD98059 reduced the cytoprotective effect of PCF. On the other hand, the JNKs and p38 inhibitor SP600125 and SB203580 additively enhanced the cytoprotective effect of PCF. We concluded that the activation of JNKs and p38 kinase played an important role in UVB-induced apoptosis, and PCF likely exerted its cytoprotective effect in thymocytes through ERKs activation. These suggested that part of the antiapoptotic effect of PCF might be mediated by its ability to modulate the MAPKs cascade.

Analysis of Variance↗

PubMed2005

Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer.

Cyclooxygenase (COX)-2 and its product prostaglandin (PG) E2 underlie an immunosuppressive network that is important in the pathogenesis of non-small cell lung cancer. CD4+ CD25+ T regulatory (Treg) cells play an important role in maintenance of immunologic self-tolerance. CD4+ CD25+ Treg cell activities increase in lung cancer and appear to play a role in suppressing antitumor immune responses. Definition of the pathways controlling Treg cell activities will enhance our understanding of limitation of the host antitumor immune responses. Tumor-derived COX-2/PGE2 induced expression of the Treg cell-specific transcription factor, Foxp3, and increased Treg cell activity. Assessment of E-prostanoid (EP) receptor requirements revealed that PGE2-mediated induction of Treg cell Foxp3 gene expression was significantly reduced in the absence of the EP4 receptor and ablated in the absence of the EP2 receptor expression. In vivo, COX-2 inhibition reduced Treg cell frequency and activity, attenuated Foxp3 expression in tumor-infiltrating lymphocytes, and decreased tumor burden. Transfer of Treg cells or administration of PGE2 to mice receiving COX-2 inhibitors reversed these effects. We conclude that inhibition of COX-2/PGE2 suppresses Treg cell activity and enhances antitumor responses.

Animals↗

PubMed2005

PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells.

Control of apoptosis is fundamental for dendritic cell (DC) homeostasis. Numerous factors maintain DC viability throughout their lifespan, including inhibitor of apoptosis proteins. Among them, survivin is overexpressed in many human malignancies, but its physiological function in normal cells has not been fully delineated. Prostaglandin E2 (PGE2), also overproduced in several malignancies, has shown to induce proapoptotic and antiapoptotic effects in different cell types, including immune cells. In DC, PGE2 predominantly affects maturation and modulates immune functions. Here, we show that exposure of monocyte-derived DC to PGE2 (10(-5) M) for 72 h significantly increased DC survivin mRNA and protein expression. In contrast, DC, matured with lipopolysaccharide or tumor necrosis factor alpha, did not reveal survivin induction in response to PGE2. Following exposure to apoptotic stimuli, DC treated with PGE2 exhibited an overall increased viability compared with control DC, and this effect was correlated inversely with caspase-3 activation. Moreover, PGE2-treated, survivin-deficient DC demonstrated reduced viability in response to apoptotic stimuli. Further analysis indicated that PGE2 induced DC survivin expression in an E prostanoid (EP)2/EP4 receptor and phosphatidylinositol-3 kinase-dependent manner. These findings suggest that PGE2-dependent regulation of survivin is important in modulating apoptosis resistance in human DC.

Apoptosis↗

PubMed2005

Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo.

The retinoid cycle is a recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. Photoreceptor-specific retinol dehydrogenase (prRDH) catalyzes reduction of all-trans-retinal to all-trans-retinol and is thought to be a key enzyme in the retinoid cycle. We disrupted mouse prRDH (human gene symbol RDH8) gene expression by targeted recombination and generated a homozygous prRDH knock-out (prRDH-/-) mouse. Histological analysis and electron microscopy of retinas from 6- to 8-week-old prRDH-/- mice revealed no structural differences of the photoreceptors or inner retina. For brief light exposure, absence of prRDH did not affect the rate of 11-cis-retinal regeneration or the decay of Meta II, the activated form of rhodopsin. Absence of prRDH, however, caused significant accumulation of all-trans-retinal following exposure to bright lights and delayed recovery of rod function as measured by electroretinograms and single cell recordings. Retention of all-trans-retinal resulted in slight overproduction of A2E, a condensation product of all-trans-retinal and phosphatidylethanolamine. We conclude that prRDH is an enzyme that catalyzes reduction of all-trans-retinal in the rod outer segment, most noticeably at higher light intensities and prolonged illumination, but is not an essential enzyme of the retinoid cycle.

Alcohol Oxidoreductases↗

PubMed2005

The role of G proteins in the activity and ethanol modulation of glycine-induced currents in rat neurons freshly isolated from the ventral tegmental area.

In freshly isolated neurons of the ventral tegmental area of young rats, we first examined the role of G proteins in the functional modulation of the glycine receptor (GlyR). GTP-gamma-S [guanosine-5'-0-(2-thiotriphosphate)] (2 mM) or GDP-beta-S [guanosine 5'-0-(2-thiodiphosphate)] (2 mM) was added to the pipette solution of whole-cell recordings to regulate G protein activities. GTP-gamma-S enhanced the amplitude of glycine-induced current (I(Gly)), suggesting modulation of GlyRs via a G protein-coupled pathway. GDP-beta-S suppressed I(Gly), suggesting that basal G protein activity positively modulates the GlyRs. We next examined effects of G proteins in ethanol potentiation of GlyR function. Activation of G proteins with 2 mM GTP-gamma-S attenuated, but did not eliminate, ethanol-induced potentiation of I(Gly). These results suggest that GTP-gamma-S and ethanol share the same pathway of activating GlyRs. When G proteins are maximally activated by GTP-gamma-S, the action of ethanol was partially occluded. When 2 mM GDP-beta-S was added in pipette solution, ethanol-induced potentiation of I(Gly) was significantly attenuated, suggesting that GDP-beta-S partially blocked the action of ethanol. However, the inability of GTP-gamma-S (or GDP-beta-S) to eliminate completely the potentiating effect of ethanol indicates that some other factors, in addition to G proteins, may also contribute to the action of ethanol on GlyRs.

Acetaldehyde↗

PubMed2005

Additive bone-protective effects of anabolic treatment when used in conjunction with RANKL and tumor necrosis factor inhibition in two rat arthritis models.

OBJECTIVE: To investigate whether the bone-preserving effects of a RANKL antagonist or a tumor necrosis factor (TNF) antagonist could be further improved by the addition of a bone anabolic agent in inflammatory arthritis. METHODS: Lewis rats with either adjuvant-induced arthritis (AIA) or collagen-induced arthritis (CIA) were treated for 10 days with PEGylated soluble tumor necrosis factor receptor type I (PEG sTNFRI), interleukin-1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), parathyroid hormone (PTH), or combinations of these agents starting on day 4 after disease onset. Treatment effects were assessed clinically, radiologically, and histologically, and by morphometry for the extent of paw swelling, bone erosive changes, and synovial inflammation. RESULTS: Paw swelling and synovial inflammation were significantly inhibited by PEG sTNFRI in AIA and CIA, and by IL-1Ra in CIA. OPG and PTH had no significant effect on these parameters. Analysis of bone erosion revealed a significant bone-sparing effect of monotherapy with PEG sTNFRI or OPG in both models, whereas IL-1Ra was only effective in CIA. PTH treatment alone did not show a bone-protective effect in either model. With the combination of PEG sTNFRI and PTH, erosion scores (-74% in AIA and -61% in CIA versus controls) were significantly lower than those elicited by PEG sTNFRI alone (-41% and -29%, respectively, versus controls). Similar results were also obtained with the combination of OPG and PTH (-88% in AIA and -73% in CIA, compared with -70% and -55%, respectively, with OPG monotherapy). Coadministration of IL-1Ra and PTH had no synergistic bone-sparing effect. Morphometric analysis revealed that the addition of PTH to PEG sTNFRI or OPG resulted in higher bone volume and higher osteoblast numbers in both AIA and CIA. CONCLUSION: The bone-protective effects resulting from RANKL or TNF antagonism can be further improved by the addition of a bone anabolic agent.

Animals↗

PubMed2005

Analysis of the kinetics of osteoclastogenesis in arthritic rats.

OBJECTIVE: To analyze the kinetics of osteoclastogenesis in 2 models of chronic immune-mediated arthritis and 1 model of acute arthritis. METHODS: Adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) in Lewis rats were used as models of chronic arthritis. Acute arthritis was induced in Lewis rats by injecting carrageenan into the hind paw. Osteoclasts were identified by cathepsin K immunohistochemistry at various time points after the onset of arthritis. The location, size, and nucleation of osteoclasts were also analyzed. RESULTS: In both AIA and CIA, multinucleated and cathepsin K-positive osteoclasts first were observed on the day of disease onset. Initially, osteoclasts were localized at the periosteum next to the synovial membrane and in subchondral bone channels. The number, size, and nucleation of osteoclasts rapidly increased, leading to severe bone loss within days after disease onset. In addition, numerous mononucleated cathepsin K-positive osteoclast precursor cells emerged in the synovial membrane. All osteoclasts (cathepsin K-positive, multinucleated, attached to bone) and osteoclast precursors (cathepsin K-positive, mononucleated or multinucleated, within synovial tissue) were also positive for a macrophage-specific marker. Upon induction of acute arthritis with carrageenan, osteoclasts formed transiently in subchondral bone, but regressed 7 days after disease onset. CONCLUSION: Functional osteoclasts are generated at the earliest stage of arthritis, and new precursors are continuously formed in the synovial membrane to replenish the osteoclast pool. These data indicate that anti-resorptive therapies may provide the most effective bone protection, when treatment is started soon after the onset of arthritis.

Acute Disease↗

PubMed2005

Effects of development and iron status on ceruloplasmin expression in rat brain.

The increased iron content in the brain of subjects with aceruloplasminemia has implicated ceruloplasmin (CP) as a major factor in the regulation of regional brain iron content. In this study, we investigated the effects of age and iron on CP expression in rat brain. In all four regions, the iron concentrations increased with developmental age. There is a similar trend in age-induced changes in CP mRNA and protein. The CP mRNA and protein levels were both lowest at postnatal day (PND) 7. The expression increased gradually with age, reaching the highest at PND196 in the striatum and substantia nigra, and at PND21 and PND63 in the cortex and hippocampus, respectively. This suggests the existence of an age-dependent pre-transcriptional regulation and a regionally specific effect of age on CP expression in the brain. Although total iron in all four regions was significantly lower in the rats fed with a low-iron diet for 6 weeks and higher in the rats with a high-iron diet than those in the control animals, no significant between-group differences in CP mRNA and protein were found in these animals, except in the substantia nigra where a significant increase in CP protein in high-iron rats was observed, and the reverse in low-iron rats. These findings suggested that the effects of iron on CP expression in the brain may be region-specific, and that regulation of CP expression by iron in the substantia nigra was at the post-transcriptional level.

Aging↗

PubMed2005

Narrow QRS tachycardia with ventriculoatrial dissociation mediated by a left fasciculoventricular fiber.

A 30-year-old man presented with narrow QRS tachycardia. The intracardiac electrocardiogram showed an atrial-HIS (AH) interval of 75 msec and a HIS-ventricular (HV) interval of 44 msec during baseline. Atrial incremental pacing revealed HV shortening, with apparent incomplete right bundle branch block (RBBB) morphology without QRS complex axis deviation. The induced tachycardia exhibited several QRS morphologies: a narrow QRS, complete RBBB and complete left bundle branch block (LBBB) morphology. Spontaneous conversion of the QRS pattern from wide to narrow was observed. The cycle length of the tachycardia was significantly shortened (from 316 to 272 ms) from LBBB morphology to narrow QRS complex. The atrial activation was dissociated from the ventricular activation during all tachycardias. Each QRS complex during tachycardia was preceded by a HIS deflection and HV interval was 35 ms, which was shorter than that of sinus rhythm. HIS deflection was earlier than right bundle potential during all kinds of tachycardia. This tachycardia is most likely mediated by a left fasciculoventricular fiber which connects the HIS bundle below the atrioventricular node to the myocardial tissue of the left ventricle. The HIS-Purkinje system is used as an antegrade conduction limb and the fasciculoventricular fiber as a retrograde limb in the tachycardia circuit.

Adult↗

PubMed2005

Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain.

The DMT1(Nramp2/DCT1) is a newly discovered proton-coupled metal-ion transport protein. The cellular localization and functional characterization of DMT1 suggest that it might play a role in physiological iron transport in the brain. In the study, we evaluated effects of dietary iron and age on iron content and DMT1 expression in four brain regions: cortex, hippocampus, striatum, substantia nigra. Total iron content in all regions was significantly lower in the low-iron diet rats and higher in the high-iron diet rats than that in the control animals, showing that dietary iron treatment for 6-weeks can alter brain iron levels. Contrary to our expectation, there was no significant alternation in DMT1(+IRE) and (-IRE) mRNA expression and protein content in all brain regions examined in spite of the existence of the altered iron levels in these regions after 6-weeks' diet treatment although TfR mRNA expression and protein level were affected significantly, as was expected. The data demonstrates that expression of DMT1(+IRE) and (-IRE) was not regulated by iron in these regions of adult rats. The lack of response of DMT1 to iron status in the brain suggests that the IRE of brain DMT1 mRNA might be not really iron-responsive and that DMT1-mediated iron transport might be not the rate-limiting step in brain iron uptake in adult rats. Our findings also showed that development can significantly affect brain iron and DMT1(+IRE) and (-IRE) expression but the effect varies in different brain regions, indicating a regionally specific regulation in the brain.

Age Factors↗

PubMed2005

Drug 'hot-spots', alcohol availability and violence.

Ecological studies have shown a relationship between alcohol outlet densities and violence and between the location of crimes related to illicit drug use (so-called 'hot spots') and violence. To date, no study has compared the effects of alcohol outlets and drug hot spots on rates of violence. The present study examined this relationship in the City of Houston, Texas. An ecological study design was employed, using a sample of 439 census tracts from Houston, Texas. Neighborhood socio-structural, alcohol outlet density, drug crime density and violent crime density data were collected from archival sources and analyzed using multivariate and spatial statistics. Using ordinary least-squares analysis, the neighborhood socio-structural covariates explained about 40% of the variability in violent crime. Adding alcohol outlet density in the target census tracts explained an additional 6%, while the addition of drug crime density explained an additional 32%. In the final model, that controlled for the effects of autocorrelated error, both drug crime density in the target and adjacent census tracts remained significant predictors of violent crime, while only off-sale density in the target census tract remained significant in the model. The findings indicate that drug crime density explained a greater amount of variance in violent crime rates than the alcohol outlet density. The methodological and policy implications of these findings are discussed, along with the shortcomings of the analysis presented.

Alcohol Drinking↗

PubMed2005

Minding the gaps to promote thrombus growth and stability.

Efforts to understand the role of platelets in hemostasis and thrombosis have largely focused on the earliest events of platelet activation, those that lead to aggregation. Although much remains to be learned about those early events, this Review examines a later series of events: the interactions between platelets that can only occur once aggregation has begun, bringing platelets into close contact with each other, creating a protected environment in the gaps between aggregated platelets, and fostering the continued growth and stability of the hemostatic plug.

Animals↗

PubMed2005

Antioxidant effects of dehydroepiandrosterone are related to up-regulation of thioredoxin in SH-SY5Y cells.

Neuroprotective effects of dehydroepiandrosterone (DHEA) have been shown to be associated with its antioxidant properties, but the mechanisms remain unknown. Considering that the thioredoxin (Trx) system, an important cellular redox modulation system, changes under oxidative stress and could exert protective effects, the relationship between the antioxidant effects of DHEA and the Trx system regulation was explored. Using MTT assay and morphological observation, the effects of DHEA in the model of H2O2-induced oxidative stress in SH-SY5Y cells were analyzed, then RT-PCR and Western blot assay were used to detect the alteration in mRNA and protein level of Trx. The results showed that a pre-treatment of DHEA (10-100 nM) protected cells against the toxicity induced by H2O2 in a dose-dependent manner, which could be confirmed in morphological observation by phase-contract microscope. In addition, Trx mRNA transcription was inhibited by H2O2 (300 microM), which could be reversed by the pre-administration of DHEA in various concentrations (0.1100 nM). Western blot assay confirmed that protein level of Trx could be elevated by the pre-treatment of DHEA (10100 nM) with the exposure of H2O2. Taken together, these data suggest that DHEA may be useful in treating age-related neurodegenerative diseases based on its up-regulating effects on an antioxidant and neuroprotective protein thioredoxin, a substrate in the Trx redox system.

Antioxidants↗

PubMed2005

[Anatomic study on the recurrent laryngeal nerve in thyroid surgery].

OBJECTIVE: To study the anatomic characteristic and dissecting approach of recurrent laryngeal nerve in thyroid surgery. METHOD: A retrospective review of surgical data of consecutive 56 patients undertook thyroid surgery was conducted, in which total 63 recurrent laryngeal nerves were identified. RESULT: A nerve bifurcation was found in 48 recurrent laryngeal nerves. Twenty-nine nerves were deep to the inferior thyroid artery, 19 were superficial to the artery, 8 were between the arteries. The inferior thyroid artery was not found in 7 cases. CONCLUSION: Correct identification and safe dissection of the recurrent laryngeal nerve are essential in thyroid surgery.

Adult↗

PubMed2005

[Prevention of Rhodiola-astragalus membranaceus compounds against simulated plateau hypoxia brain injury in rat].

OBJECTIVE: To observe the protective effects of Rhodiola-astragalus membranaceus mixture against brain damage during hypoxia under simulated plateau environment and the mechanisms maybe involved in. METHOD: Adult SD rats were randomly divided into 3 groups, which were normoxic control, simulated plateau hypoxia, and Rhodiola-astragalus membranaceus mixture pretreatment group. Rats in the latter two groups were exposed to simulated 8000 m altitude in a hypobaric chamber for 7 h. Water content, Na+, K(+)-ATPase activity and SOD activity in cerebral tissue, malondialdehyde (MDA) and lactic acid content in cerebral homogenate and serum were measured. RESULT: As compared with control group, cerebral water content was significantly higher in hypoxia group, while it was obviously lower in pretreatment group. MDA contents of hypoxia group both in cerebral homogenate and serum were higher than that of control group, while the pretreatment group they were both decreased obviously. Lactic acid content of hypoxia group in cerebral and in serum increased markedly and decreased drastically in pretreatment group compared to that of hypoxic group. CONCLUSION: Rhodiola-astragalus membranaceus mixture has preventive effects on hypoxic damage induced by simulated plateau environment. This prevention may be related to the antagonistic effect on membrane lipid peroxidation and the inhibition on the accumulation of lactic acid in brain tissue and serum.

Adenosine Triphosphatases↗

PubMed2005

[The genetic effects of MyoG gene].

The PCR-RFLP technique was applied in this study to analyze the MspI polymorphism in the 3-UTR of MyoG gene. The relationship between different genotypes and corresponding traits and the genetic effects of different allele were analyzed. The results indicated that the N allele has highly significant genetic effects in improving carcass lean percent and the loin eye area, and decreasing the fat content (P<0.01). But no significant influence was found to the FOM carcass traits (P>0.05). As meat quality traits being considered, the N allele highly significantly decreased the pH value, meat color, intramuscular fat content, increased the drip loss (P<0.01) and caused the worse of meat quality. When considering genetic values of different traits, it was found that the N allele had additive effects of 3.929% to carcass lean percent, 2.0985 cm2 to loin eye area, -3.0245% to the fat content, -0.167 to the pH1 value, 0.558% to the drip loss and -0.963% to intramuscular fat content. But no effect was observed to the carcass grading traits.

Alleles↗

PubMed2005

[A field trial for evaluating the safety of recombinant human interferon alpha-2b for nasal spray].

OBJECTIVE: To evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections. METHODS: Field epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days. RESULTS: During the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies. CONCLUSION: Using recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Abdominal Pain↗

PubMed2005

[The genetic diversity and genetic effects of Myf-6 gene in different pig breeds].

As a member of MRFs, Myf-6 gene plays an important role in the progress of myogenesis. The PCR-RFLP technique was applied in this study to analyze the distribution of Myf-6 gene in 12 different pig breeds and hybrid breeds. The genetic effects of Myf-6 gene on muscle fiber, carcass quality, carcass grading traits and meat quality traits were analyzed. The results indicated that: The polymorphisms of Myf-6/Ava I genotypes (intron1) were not abundant. Most of Chinese native pigs were AA homozygotes. B allele can be found only in foreign pig breeds and hybrid pigs originated from foreign pig breeds. Although no BB individuals were found in the experiment, the carcass lean percent of AB individuals (50.344 %) was significantly higher than that of AA individuals (45.875 %)(P<0.01), the loin eye area of AB individuals (27.097 cm2) was significantly larger than that of AA individuals (22.572 cm2)(P<0.01), and the carcass fat content of AB individuals (39.889 %) was significantly lower than that of AA individuals (44.503 %)(P<0.01). That means that the B allele can increase carcass lean percent and loin eye area, and decrease the carcass fat content, thus cause better carcass quality. No significant effects of the genotypes were found on the muscle fiber, FOM carcass grading traits and meat quality traits (P>0.05).

Alleles↗