Biomedical subjects

Ji Li

Publications and source records attributed to Ji Li.

At least 55 records · Page 3Linked to original sources

PubMed2004

Elevated gadd153/chop expression and enhanced c-Jun N-terminal protein kinase activation sensitizes aged cells to ER stress.

The endoplasmic reticulum (ER), as a processing plant for the folding and posttranslational modification of proteins, is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed 'ER stress', can perturb ER functions, leading to the activation of a complex response known as the unfolded protein response. Here, we investigated the response of hepatocytes derived from young (4-5 months) and aged (24-26 months) rats to two agents, thapsigargin (TG) and tunicamycin (TM), which act via different mechanisms to induce ER stress. Old hepatocytes displayed greater cell death than young cells following treatment with TG or TM, associated with higher expression of the pro-apoptotic gene gadd153 (also known as chop) and enhanced c-Jun N-terminal protein kinase (JNK) activation. Pharmacologic inhibition of JNK decreased the expression of TG-stimulated gadd153 in old cells and reduced their sensitivity to TG-induced cell death. Inhibition of p38, on the other hand, enhanced TG-induced gadd153 expression and JNK activation, and augmented TG-induced cell death. Additional experiments implicated the PERK/eIF-2 alpha signaling pathway as a contributor to the higher Gadd153 expression and JNK activation, and greater sensitivity of old cells to ER stress.

Aging↗

PubMed2004

Post-traumatic bilateral facial palsy: a case report and literature review.

Bilateral facial paralysis due to basilar skull fracture involving the temporal bone is rare and, unlike unilateral facial palsy, it can be difficult to recognize because of a lack of facial asymmetry. Thorough clinical history and physical exam, high-resolution CT scan and electrodiagnostic tests can help to make the diagnosis of bilateral facial nerve palsy and early detection, evaluation and intervention may be important for optimal functional recovery. A 16-year-old male sustained closed head injury after motor vehicle collision. The initial head CT scan showed bilateral temporal bone fractures. On admission to the neurotrauma intensive care unit, his Glasgow Coma Score was 9T. On post-injury day 4, the patient was noted to have incomplete closure of both eyes and 3 days later he had difficulty with bilateral facial muscle movement during a feeding trial. Electrodiagnostic testing confirmed the diagnosis of bilateral facial nerve injury without evidence of significant distal axonal degeneration. A high-resolution CT scan showed bilateral temporal bone fractures without involvement of the fallopian canals. There was no surgical intervention based on the high-resolution CT scan and the delayed onset of facial palsy. A short course of prednisone was administered. By 10 months, the patient showed nearly complete recovery of his bilateral facial nerve function. Early detection, evaluation and intervention are important for optimal functional recovery after facial nerve injury. When the temporal bone is fractured, high suspicion for facial nerve injury, either unilateral or bilateral, is warranted.

Adolescent↗

PubMed2004

AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury.

AMP-activated protein kinase (AMPK) is an important regulator of diverse cellular pathways in the setting of energetic stress. Whether AMPK plays a critical role in the metabolic and functional responses to myocardial ischemia and reperfusion remains uncertain. We examined the cardiac consequences of long-term inhibition of AMPK activity in transgenic mice expressing a kinase dead (KD) form of the enzyme. The KD mice had normal fractional shortening and no heart failure, cardiac hypertrophy, or fibrosis, although the in vivo left ventricular (LV) dP/dt was lower than that in WT hearts. During low-flow ischemia and postischemic reperfusion in vitro, KD hearts failed to augment glucose uptake and glycolysis, although glucose transporter content and insulin-stimulated glucose uptake were normal. KD hearts also failed to increase fatty acid oxidation during reperfusion. Furthermore, KD hearts demonstrated significantly impaired recovery of LV contractile function during postischemic reperfusion that was associated with a lower ATP content and increased injury compared with WT hearts. Caspase-3 activity and TUNEL-staining were increased in KD hearts after ischemia and reperfusion. Thus, AMPK is responsible for activation of glucose uptake and glycolysis during low-flow ischemia and plays an important protective role in limiting damage and apoptotic activity associated with ischemia and reperfusion in the heart.

AMP-Activated Protein Kinases↗

PubMed2004

Inhibitors of 5-lipoxygenase inhibit expression of intercellular adhesion molecule-1 in human melanoma cells.

AIM: To study the effect of 5-lipoxygenase inhibitors on the expression of intercellular adhesion molecule-1 (ICAM-1) in melanoma cells. METHODS: ICAM-1 protein of human melanoma cell a375 was detected by enzyme-linked immunosorbent, flow cytometry and Western blot analysis. Level of ICAM-1 mRNA in a375 was evaluated by Northern blot analysis. Adhesion of a375 to endothelial cell EC304 was analyzed by isotopic tracing. RESULTS: 5-Lipoxygenase inhibitors nordihydroguaiaretic acid, AA861 and MK886, could suppress the expression of ICAM-1 protein as well as of its mRNA in a375 cells and reduce the adhesion of a375 to EC304. CONCLUSION: 5-Lipoxygenase inhibitors can inhibit the expression of ICAM-1 in human melanoma cells and may be valuable for treatment of melanoma metastasis.

Benzoquinones↗

PubMed2004

[Pathologic diagnosis and differential diagnosis of pulmonary Langerhans' cell histiocytosis].

OBJECTIVE: Morphologic findings of pulmonary Langerhans' cell histiocytosis were analyzed in order to delineate diagnostic features. METHODS: H&E staining and immunohistochemical studies were performed on 7 cases of pulmonary Langerhans' cell histiocytosis. RESULTS: Infiltration by Langerhan's cells was obvious in all 7 cases. Inflammatory cell infiltrates, interstitial fibrosis and focal necrosis may also be seen. The cells expressed S-100 (7/7), CD68 (3/7), and CD1a (5/5). CONCLUSIONS: In case there is radiologic suspicion of Langerhans' cell histiocytosis, pulmonary biopsy is strongly advised for a definitive diagnosis. S-100 and CD1a immunostaining is also helpful in this respect.

Adolescent↗

PubMed2004

[The study on expression of bFGF and quantity of mast cell in infant hemangiomas of grandulae parotid gland].

The qualitative and quantitative study on mast cells and bFGF in 40 cases of infant hemangiomas of the grandulae parotid and 5 cases of normal grandulae parotid tissues were investigated by special mast cell staining methods, immunohistochemistry and image analysis technique. The quantity, area and average density of MC remarkably increased, there were significant differences. The mast cells mainly distributed around premature blood vessels and in parotid gland leaves; bFGF was highly expressed in infant hemangiomas of grandulae parotid. Its immuno-reactivity was present in the cytoplasm of endotheliocytes,mainly in extracellular matrix, distributed in light reticulation. It is concluded that there was a close relationship between bFGF and mast cell in proliferation of infant hemangiomas of grandulae parotid.

Female↗

PubMed2003

IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms.

IL-27, a novel heterodimeric cytokine produced by antigen-presenting cells, signals through the T cell cytokine receptor (TCCR)/WSX-1 expressed on naïve CD4+ T cells and natural killer cells. TCCR/WSX-1 deficiency results in delayed T helper type 1 (TH1) development through an unresolved mechanism. We report here that IL-27 stimulation in developing murine T helper cells potently induces the expression of the major TH1-specific transcription factor T-bet and its downstream target IL-12R beta2, independently of IFN gamma. In addition, IL-27 suppresses basal expression of GATA-3, the critical TH2-specific transcription factor that inhibits TH1 development by down-regulating signal transducer and activator of transcription (Stat) 4. IL-27 signaling through TCCR/WSX-1 induces phosphorylation of Stat1, Stat3, Stat4, and Stat5. Stat1 is required for suppression of GATA-3, but T-bet induction by IL-27 can also be mediated through a Stat1-independent pathway. Despite its TH1-like signaling profile, IL-27 is not sufficient to drive the differentiation of CD4+ T cells into IFN gamma-producing cells. Similarly, IL-27 induces T-bet expression in primary natural killer cells, but this does not result in an increase of IFN gamma production or cytotoxic activity. Therefore, although IL-27 is unable to drive IFN gamma production on its own, it plays an important role in the early steps of TH1 commitment by contributing in a paracrine manner to the control of IL-12 responsiveness.

Animals↗

PubMed2003

The muscle integrin binding protein (MIBP) interacts with alpha7beta1 integrin and regulates cell adhesion and laminin matrix deposition.

Integrins are alphabeta transmembrane receptors that function in key cellular processes, including cell adhesion, differentiation, and extracellular matrix deposition through interactions with extracellular, membrane, and cytoplasmic proteins. We previously identified and cloned a muscle beta1 integrin cytoplasmic binding protein termed MIBP and found that the expression level of MIBP is critical in the decision-making process of terminal myogenic differentiation. We report here that MIBP interacts with the alpha7beta1 integrin but not the alpha5beta1 integrin in C2C12 myoblasts, suggesting an important role of integrin alpha chains in the regulation of the beta1-MIBP interaction. Furthermore, consistent with its selective binding activity toward the alpha7beta1 laminin receptor, we have found that overexpression of MIBP in C2C12 myoblasts resulted in a significant reduction of cell adhesion to laminin and inhibition of laminin matrix deposition. By contrast, neither cell adhesion to fibronectin nor fibronectin matrix deposition was significantly altered in cells overexpressing MIBP. Finally, we show that both the protein level and tyrosine phosphorylation of paxillin, a key signaling molecule involved in the cellular control of myogenic differentiation, are increased by MIBP. These results suggest that MIBP functions in the control of myogenic differentiation by regulating alpha7beta1 integrin-mediated cell interactions with laminin matrix and intracellular signaling through paxillin.

Amino Acid Sequence↗

PubMed2003

Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance.

Although recent evidence suggests that leptin can directly regulate a wide spectrum of peripheral functions, including fat metabolism, genetic examples are still needed to illustrate the physiological significance of direct actions of leptin in a given peripheral tissue. To this end, we used a technical knock-out approach to reduce the expression of leptin receptors specifically in white adipose tissue. The evaluation of leptin receptor reduction in adipocytes was based on real time PCR analysis of the mRNA levels, Western blot analysis of the proteins, and biochemical analysis of leptin signaling capability. Despite a normal level of leptin receptors in the hypothalamus and normal food intake, mutant mice developed increased adiposity, decreased body temperature, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and insulin sensitivity, as well as elevated hepatic and skeletal muscle triglyceride levels. In addition, a variety of genes involved in regulating fat and glucose metabolism were dysregulated in white adipose tissue. These include tumor necrosis factor-alpha, adiponectin, leptin, fatty acid synthase, sterol regulatory element-binding protein 1, glycerol kinase, and beta3-adrenergic receptor. Furthermore, the mutant mice are significantly more sensitive to high fat feeding with regard to developing obesity and severe insulin resistance. Thus, we provide a genetic model demonstrating the physiological importance of a peripheral effect of leptin in vivo. Importantly, this suggests the possibility that leptin resistance at the adipocyte level might be a molecular link between obesity and type 2 diabetes.

Adipocytes↗

PubMed2003

Common mechanisms for declines in oxidative stress tolerance and proliferation with aging.

Aging is often characterized by reduced stress tolerance and decreased proliferative capacity, but little is known about the effects of aging on signaling pathways important in regulating these responses. Recent studies from our laboratory have implicated impairments in epidermal growth factor receptor (EGFR) signaling and extracellular signal-regulated kinase (ERK) activation to both effects in rat hepatocytes. Here we investigated the responsiveness of hepatocytes derived from young (4-5 months) and aged (24-29 months) mice to proliferative signals (low concentrations of H2O2 and epidermal growth factor [EGF] stimulation), and oxidant injury (high H2O2 concentrations). Old hepatocytes displayed lower levels of DNA synthesis in response to low H(2)O(2) concentrations (5-10 microM) and EGF stimulation, and reduced survival following treatment with high H2O2 concentrations (20-50 microM). Both effects were associated with reduced activation of ERK and diminished phosphorylation of EGFR tyrosine residue 1173. p38 was also activated by H2O2, but to a greater extent in old cells. Pharmacologic inhibition of ERK increased the sensitivity of young cells to H2O2-induced cell death, while inhibition of p38 decreased the sensitivity of old cells. Our findings suggest that impairments in common signaling events underlie age-related declines in proliferative capacity and oxidative stress tolerance in mouse hepatocytes, and that an imbalance in ERK and p38 activities contributes to the greater sensitivity of aged cells to H2O2.

Aging↗

PubMed2003

Expression of the pro-apoptotic gene gadd153/chop is elevated in liver with aging and sensitizes cells to oxidant injury.

Aging is generally accompanied by reduced tolerance to oxidative stress and altered responsiveness to proliferative signals. We have shown that hepatocytes derived from aged rats (24-26 months) exhibit greater sensitivity to H(2)O(2) treatment and reduced proliferation following epidermal growth factor (EGF) treatment than cells of young adult rats (5-6 months). Here we examined the effects of aging and calorie restriction (CR) on expression of the oxidative stress-inducible and pro-apoptotic gene gadd153 (chop) in these hepatocytes, and we investigated its influence on sensitivity to oxidants. We show that aging was associated with elevated expression of gadd153, both basally and in response to H(2)O(2) treatment. CR, which attenuates age-associated declines in stress tolerance, prevented the age-related increase in gadd153 expression. EGF treatment also resulted in gadd153 induction in old cells. This effect was absent in young cells and in old cells of CR rats. gadd153 induction by EGF was reactive oxygen species-dependent and correlated with heightened sensitivity to subsequent H(2)O(2) treatment, suggesting that elevated Gadd153 contributes to the greater sensitivity of EGF-pretreated old cells to oxidative stress. Additional support for this hypothesis was provided by experiments with Rat1 fibroblasts in which conditional expression of Gadd153 conferred increased sensitivity to H(2)O(2). We propose a model whereby the diminished ability of old hepatocytes to overcome an EGF-triggered reactive oxygen species load leads to induction of the proapoptotic gene gadd153, which, in turn, sensitizes the cells to oxidant injury. Our findings point to gadd153 expression levels as an important factor in liver aging.

Aging↗

PubMed2003

Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts.

Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including proto-oncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK- selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process.

Acetylation↗

PubMed2003

Application of intake fraction to population exposure estimates in Hunan Province of China.

This article developed a new method, based on the concept of "intake fraction", to assess population exposure to primary and secondary fine particle matters from site-specific sources. This method was illustrated by a set of 17 power plants (totally 24 stacks) in Hunan Province of China. The CALPUFF long-range atmospheric dispersion model was used to simulate ambient concentrations of fine particles, and the GIS technology was used to generate a population distribution database from county-level population statistical data. An integrated computer program package was developed to carry out numerical integration of dispersion results over the population data, and produce intake fractions. The resulting average intake fractions within 500 km were 9.73 x 10(-6), 2.39 x 10(-6), and 2.47 x 10(-6) for primary fine particles, sulfate and nitrate respectively. Regression analyses were performed to explore the relationships between intake fractions and potential variables. Results showed that the stack height and aggregate populations could be used to predict intake fractions of fine particles. R2 of the regression equations were 0.83, 0.64, and 0.74 for primary fine particles, sulfate and nitrate respectively. Iso-intake fractions presenting geographical distributions of intake fractions in Hunan Province were mapped, showing a factor of about 2 between the highest values in the northeast and the lowest in the southwest of Hunan Province.

Air Pollutants↗

PubMed2003

The free deltoid flap: microscopic anatomy studies and clinical application to oral cavity reconstruction.

The deltoid free flap is a fasciocutaneous flap that should be thin, hairless, of an adequate size, and capable of sensory reinnervation. Because of its excellent color-matching and texture-matching characteristics, it has recently been widely used for the reconstruction of soft-tissue defects during oral and maxillofacial surgery. Furthermore, a characteristic of oral and maxillofacial soft-tissue defects is that they are not large; therefore, flap size will be small, allowing the donor site to be directly closed. Because of natural variation in parts of the anatomy, there has sometimes been great difficulty in clinical application. The authors decided to study this by performing anatomical studies of the deltoid region on 21 cadavers. The result indicates that the pedicle of the deltoid free flap penetrates the "quadrangular space" in 90 percent of cases but passes and does not penetrate the quadrangular space in the remaining cases. The authors also confirmed that the skin has a vascular network comprising five layers and, furthermore, that the vascular network of the deep fascia is dense. The authors also report six cases of its clinical use complicated by anatomic variation and local infection in which the deltoid flap showed a completely successful outcome.

Aged↗

PubMed2003

[Population exposure to air pollutant emissions in Human Province].

Estimate of population exposure to air pollution is necessary to health impact assessment. Based on the concept of intake fraction, a rapid population exposure assessment method was developed in this paper. The CALPUFF atmospheric dispersion model was applied to estimate intake fractions of primary and secondary fine particles emitted from a set of 17 power plants in Hunan Province. Results showed that within 500 km from the emission source, average values of intake fraction were 9.73 x 10(-6) for PM2.5, 2.39 x 10(-6) for sulfate and 2.47 x 10(-6) for nitrate. From regression analysis, good correlations were found for the relations among intake fraction of PM2.5, stack height, and population (R2 = 0.83), and intake fraction of SO(4)2- and population (R2 = 0.64), and intake fraction of NO3-, stack height and population (R2 = 0.74). Iso-intake fraction maps were produced based on the regression equations and population distribution, which reflected the differentiation of population density and enabled simple impact assessment for emission sources in this region.

Air Pollution↗

PubMed2003

[Effects of brain-derived neurotrophic factor on H2O2-induced apoptosis of human arterial smooth muscle cell].

OBJECTIVE: To investigate the protective effects of brain-derived neurotrophic factor (BDNF) on hydrogen peroxide (H2O2) induced apoptosis of human arterial smooth muscle cells (SMC). METHODS: The hBDNF cDNA was transfected into the SMC mediated by Lipofect- AMINE, and ectopic expression in SMC was driven by the regulatory elements of I type collagen gene(COLIA1). The cell proliferation was measured with a colorimetric assay based on the cleavage of the tetrazolium salt MTT. Microscopic analysis of cell apoptosis was performed with fluorescent stain of acridine orange (AO). Apoptosis rate of SMC was tested by flow cytometry (FCM). DNA pattern was examined by agarose gel electrophoresis. RESULTS: Exposure of growing SMC to 100-800 mumol/L H2O2 for 24 h remarkably suppressed the cell proliferation. After treatment of the cells with 200 mumol/L H2O2 for 24 h, morphological and biochemical changes of classic apoptosis such as condensation of cytoplasm, fragmentation of the nuclear chromatin, DNA "ladder" pattern after electrophoresis were observed. Yet, the above-mentioned apoptosis changes were not observed and the apoptosis rate was reduced obviously in the BDNF-transfected SMC treated with the same concentration of H2O2. CONCLUSION: H2O2 can induce apoptosis of SMC, but BDNF inhibits H2O2-induced SMC apoptosis markedly and has strong anti-apoptotic activity.

Apoptosis↗

PubMed2003

Estimating health damage cost from secondary sulfate particles--a case study of Hunan Province, China.

China's coal-dominated energy pattern has resulted in large amount of SO2 emissions. Estimate of the sulfur-related health damage cost is necessary to help perform systematic cost-benefit analysis and set national energy and emissions control priorities. Current researches were confined to gaseous SO2 in urban areas; however, secondary sulfate (SO4(2-)) particles can exert serious impact in a wider region. Based on the concept of "intake fraction", CALPUFF long-range dispersion model and 180 sample emission sources, multiple regression equation was obtained with good correlation( r = 0.85), which illustrates that populations were key parameters to determine intake fraction but source characteristics were insignificant. Based on the formula and the population distribution data, county-level intake fractions were mapped for Hunan Province(range: 1.1 x 10(-6) - 3.2 x 10(-6)) of China. A combination of county-level SO2 emissions with the intake fractions yields a total 1.98 tons of sulfate(SO4(2-)) inhalation, and resulting total health damage cost to be 0.76(willingness to pay approach, WTP) or 0.16 (human capital approach, HC) billion USD in 1997, about 2.1% or 0.45% of GDP in Hunan in 1997. Average health damage cost per ton of SO2 emission is 930(WTP) or 200 USD(HC). The results demonstrated that more stringent regulation should be forced.

Air Pollutants↗

PubMed2002

Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages.

Exposure of macrophages to LPS elicits the production of proinflammatory cytokines, such as TNF-alpha, through complex signaling mechanisms. Mitogen-activated protein (MAP) kinases play a critical role in this process. In the present study, we have addressed the role of MAP kinase phosphatase-1 (MKP-1) in regulating proinflammatory cytokine production using RAW264.7 macrophages. Analysis of MAP kinase activity revealed a transient activation of c-Jun N-terminal kinase (JNK) and p38 after LPS stimulation. Interestingly, MKP-1 was induced concurrently with the inactivation of JNK and p38, whereas blocking MKP-1 induction by triptolide prevented this inactivation. Ectopic expression of MKP-1 accelerated JNK and p38 inactivation and substantially inhibited the production of TNF-alpha and IL-6. Induction of MKP-1 by LPS was found to be extracellular signal-regulated kinase dependent and involved enhanced gene expression and increased protein stability. Finally, MKP-1 expression was also induced by glucocorticoids as well as cholera toxin B subunit, an agent capable of preventing autoimmune diseases in animal models. These findings highlight MKP-1 as a critical negative regulator of the macrophage inflammatory response, underscoring its premise as a potential target for developing novel anti-inflammatory drugs.

Animals↗