Search PubMed⌕ Search

Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

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

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

Animals↗
PubMed2005

Radial elasticity of multiwalled carbon nanotubes.

We report an experimental and a theoretical study of the radial elasticity of multiwalled carbon nanotubes as a function of external radius. We use atomic force microscopy and apply small indentation amplitudes in order to stay in the linear elasticity regime. The number of layers for a given tube radius is inferred from transmission electron microscopy, revealing constant ratios of external to internal radii. This enables a comparison with molecular dynamics results, which also shed some light onto the applicability of Hertz theory in this context. Using this theory, we find a radial Young modulus strongly decreasing with increasing radius and reaching an asymptotic value of 30+/-10 GPa.

Journal Article↗
PubMed2005

Arthrobacter ardleyensis sp. nov., isolated from Antarctic lake sediment and deep-sea sediment.

Three psychrotrophic Arthrobacter strains, isolated from Antarctic lake sediment (An24, An25T) and deep-sea sediment (ZX6) were studied. Their 16S rRNA gene sequences showed highest similarities (97.0-97.9%) with those of A. nicotianae and A. protophormiae. All three strains underwent rod-coccus morphological change, had high mol% G+C content, were aerobic to slightly anaerobic, and grew between 0 degrees C and 30 degrees C, with optimal growth temperature around 25 degrees C. The cell wall peptidoglycan was A4alpha variant. DNA-DNA hybridization, physiological and chemotaxonomic studies indicated that these three strains constituted a new homogeneous genomic species within the genus Arthrobacter, for which the name Arthrobacter ardleyensis, with the type strain An25T (CGMCC 1.3685, JCM 12921) was proposed.

Aerobiosis↗
PubMed2005

Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity.

AIMS/HYPOTHESIS: Beta cell inflammation and cytokine-induced toxicity are central to autoimmune diabetes development. Lipid mediators generated upon lipoxygenase (LO) activation can participate in inflammatory pathways. 12LO-deficient mice are resistant to streptozotocin-induced diabetes. This study sought to characterise the cellular processes involving 12LO-activation lipid inflammatory mediator production in cytokine-treated pancreatic beta cells. METHODS: Islets and beta cell lines were treated with a combination of IL-1beta, IFN-gamma and TNF-alpha, or the 12LO product 12(S)-hydroxyeicosatetraenoic acid (HETE). Insulin secretion was measured using an enzyme immunoassay, and cell viability was evaluated using an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. 12LO activity was evaluated and 12LO protein levels were determined using immunoblotting with a selective leucocyte type 12LO antibody. Cellular localisation of 12LO was evaluated using immunocytochemistry. RESULTS: Basal expression of leucocyte type 12LO protein was found in human and mouse islets and in several rodent beta cell lines. In mouse beta-TC3 cells, and in human islets, cytokines induced release of 12-HETE within 30 min. Cytokine addition also induced a rapid translocation of 12LO protein from the cytosol to the nucleus of beta-TC3 cells as shown by subcellular fractionation and immunostaining. Cytokine-induced cell death and inhibition of insulin secretion were partially reversed by baicalein, a 12LO inhibitor. 12(S)-HETE inhibited beta-TC3 cell insulin release in a time- and concentration-dependent manner. Incubating beta-TC3 cells with 100 nmol/l of 12(S)-HETE resulted in a 57% reduction in basal insulin release (6 h), and a 17% increase in cell death (18 h) as compared with untreated cells. 12(S)-HETE activated the stress-activated protein kinase c-Jun N-terminal kinase and p38 within 15 min, as judged by increased kinase protein phosphorylation. CONCLUSIONS/INTERPRETATION: The data suggest that inflammatory cytokines rapidly activate 12LO and show for the first time that cytokines induce 12LO translocation. The effects of 12-HETE on insulin secretion, cytotoxicity and kinase activation were similar to the effects seen with cytokines. The results provide mechanistic information of cytokine-induced toxic effects on pancreatic beta cells and support the hypothesis that blocking 12LO activation could provide a new therapeutic way to protect pancreatic beta cells from autoimmune injury.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2005

A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.

Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4'-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4'-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 microM, as compared to the value of greater than 50 microM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 microM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 microM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.

Apoptosis↗
PubMed2005

Clinical [corrected] and pathological characteristics of Chinese patients with antineutrophil cytoplasmic autoantibody associated systemic vasculitides: a study of 426 patients from a single centre.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) are serological markers of ANCA associated systemic vasculitides (AASV), which is one of the most common multisystem autoimmune diseases. Features of Chinese patients with AASV have not been fully investigated. OBJECTIVE: To analyse the clinical and pathological characteristics of Chinese patients with AASV. METHODS: 426 Chinese patients with AASV diagnosed in the past eight years were retrospectively studied and their clinical and pathological data were analysed. RESULTS: Of the 426 patients, 87 (20.4%) were Wegener's granulomatosis, 337 (79.1%) were microscopic polyangiitis and two (0.5%) were Churg-Strauss syndrome. Only 201 of 426 (47.2%) patients were diagnosed within three months. Clinically, the patients had multisystem involvement. Altogether 371 of 426 (87.1%) had kidney involvement and 260 of 426 (61.0%) had lung involvement. The prevalences of renal involvement and fatigue were significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA; the prevalences of ophthalmic, nasal involvement, rash, and arthragia were significantly higher in patients with PR3-ANCA than those in patients with MPO-ANCA. The one and five year death rates were 13.1% and 22.4%, respectively. The percentage of patients progressing to end stage renal disease at one and five years was 15.9% and 27.1%, respectively. CONCLUSIONS: AASV is not a rare autoimmune disease in Chinese people. Kidney and lung were the most vulnerable organs. For patients with multiorgan damage, an ANCA test should be performed to make an early diagnosis and to start treatment in time.

Adolescent↗
PubMed2005

Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in a 2-year carcinogenicity study is consistent with a rat-specific mechanism of thyroid neoplasia.

The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control), 0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the treatment, increased incidences of thyroid follicular cell hyperplasia and neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There were no other treatment-related effects and no tumors at other sites. Results from previous studies indicated a number of effects in the liver and thyroid, as well as metabolic profiles that suggested nelfinavir might cause thyroid hyperplasia/neoplasia secondary to hormone imbalance by altering thyroid hormone disposition. To investigate this hypothesis, the effects of nelfinavir on gene expression in rat hepatocytes and liver slices (in vitro), thyroxine plasma clearance, and thyroid gland function were evaluated. Compared to controls, gene expression analyses demonstrated an increased expression of glucuronyltransferase (UDPGT) and CYP450 3A1 in nelfinavir-treated rat hepatocytes and liver slices. In rats treated with nelfinavir (1000 mg/kg per day) for 4 weeks, liver weights and centrilobular hepatocellular hypertrophy were increased and minimal to mild diffuse thyroid follicular cell hypertrophy and follicular cell hyperplasia were evident in the thyroid gland. Thyroid-stimulating hormone (TSH) levels were significantly increased (three-fold), while tri-iodothyronine (T3)/tetra-iodothyronine (T4) and reverse T3(rT3) levels were unchanged, indicating that a compensated state to maintain homeostasis of T3/T4 had been achieved. Plasma 125I-thyroxine clearance was increased and the plasma thyroxine AUC0-48 was decreased (24%) compared to control. In conclusion, these data indicate that thyroid neoplasms observed in the nelfinavir-treated rats were secondary to thyroid hormone imbalance. Increased thyroxine clearance contributes to the effects of nelfinavir on thyroid gland function and is probably a result of UDPGT induction that leads to elevated TSH levels in the rat and eventual thyroid neoplasia. These results are consistent with a well-recognized rat-specific mechanism for thyroid neoplasms.

Adenocarcinoma, Follicular↗
PubMed2005

Heat stress-induced modulation of host defense against Toxoplasma gondii infection in mice.

This study examined the effects of burn injury on murine immune response against Toxoplasma gondii infection. Male C57BL/6 mice were divided into 3 groups: T. gondii infection (group T), burn injury (group B), and burn injury followed by T. gondii infection (group BT). The survival of group BT was significantly lower than those of group B and group T. Parasite abundance in the tissues was determined by quantitative competitive-polymerase chain reaction. Group BT exhibited significantly higher numbers of T. gondii than group T. Antibody production against T.g.HSP30 in group BT was significantly lower than that in group T, whereas no significant difference was observed in SAG1-specific antibody production. Delayed-type hypersensitivity (DTH) specific for 2,4-dinitrofluorobenzene (DNFB) of both group B and group BT was significantly lower than that of group T. One week after infection, serum interferon-gamma (IFN-gamma) and interleukin (IL)-10 levels in group BT were significantly lower, whereas serum IL-6 levels were significantly higher than in group T Serum TNF-alpha levels in both group T and group BT were elevated at 1 wk after infection, although there was no significant difference between them. Serum IFN-gamma, IL-10, and TNF-alpha levels in group B were not elevated during the experimental term. In conclusion, the impaired antigen-specific antibody production and DTH response, together with the modulated patterns of cytokine responses, seemed to be strongly involved in the development of burn-induced immunosuppression and the consequent increased susceptibility to T. gondii infection in mice.

Animals↗
PubMed2004

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity.

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

Journal Article↗
PubMed2004

Constraints on nucleon decay via invisible modes from the Sudbury Neutrino Observatory.

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to "invisible" modes, such as n-->3nu. The analysis was based on a search for gamma rays from the deexcitation of the residual nucleus that would result from the disappearance of either a proton or neutron from 16O. A limit of tau(inv)>2 x 10(29) yr is obtained at 90% confidence for either neutron- or proton-decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton-decay modes and 400 times more stringent than similar neutron modes.

Journal Article↗
PubMed2004

Failure to confer cardioprotection and to increase the expression of heat-shock protein 70 by preconditioning with a kappa-opioid receptor agonist during ischaemia and reperfusion in streptozotocin-induced diabetic rats.

AIMS/HYPOTHESIS: The aim of this study was to determine the effects of preconditioning on injury and expression of heat shock proteins 70 in diabetic rat hearts. METHODS: Diabetes was induced by an intraperitoneal injection of 65 mg kg(-1) streptozotocin. Daily subcutaneous injection of 4 IU insulin started 2 weeks after streptozotocin treatment for 4 weeks. Rats were preconditioned by intravenous injection of 10 mg kg(-1) U50,488H, a selective kappa-opioid receptor agonist (U50,488H preconditioning). The effects of U50,488H preconditioning had previously been shown to be blocked by a selective kappa-opioid receptor antagonist, nor-binaltorphimine. Twenty-four hours later, rats were subjected to 30 min of regional ischaemia by occlusion of the left coronary artery followed by 4 h of reperfusion. Infarct size was determined at the end of reperfusion. Stress-inducible and constitutive heat shock proteins 70 were analysed at the end of ischaemia and reperfusion by Western blotting. RESULTS: Myocardial infarcts induced by ischaemia and reperfusion were greater in diabetic rats. U50,488H preconditioning significantly reduced the infarct size and increased the expression of stress-inducible heat-shock protein 70 in normal rats. The effects of U50,488H preconditioning were abolished in streptozotocin-induced diabetic rats, but restored by insulin replacement. CONCLUSION/INTERPRETATION: In addition to a greater susceptibility to ischaemic insults, the delayed cardioprotection of U50,488H preconditioning was lost, which could at least partly be due to impaired synthesis of stress-inducible heat-shock protein 70 in diabetic rats.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2004

Risk factors and clinical outcomes of nosocomial multi-drug resistant Pseudomonas aeruginosa infections.

Risk factors for multi-drug resistant Pseudomonas aeruginosa (MDRP) infections were investigated using a case-control study design involving MDRP patients (N = 44) and controls (N = 68). A retrospective cohort study was performed to study the predictive factors of clinical outcome in MDRP patients. Multivariate analysis demonstrated that previous exposure to imipenem/meropenem [odds ratio (OR), 44.8] and mechanical ventilation (OR 8.2) were risk factors for nosocomial infections of MDRP. Of 44 cases of MDRP infections, 20 patients died directly from P. aeruginosa infections. Pulsed-field gel electrophoresis (PFGE) analysis on serial isolates from three patients showed that profiles of isolates from the same patient were closely related or indistinguishable. Multivariate analysis demonstrated that patients with adverse clinical outcomes were more likely to have been treated with mechanical ventilation (OR 12.8), and more likely to have MDRP resistance patterns that did not change during treatments (OR 26.5). We concluded that mechanical ventilation and previous exposure to imipenem/meropenem were independent risk factors for MDRP infections, while mechanical ventilation and antibiotic resistance switch were predictive factors of outcomes of MDRP infections.

Adult↗
PubMed2004

Assessment of human pancreatic islets after long distance transportation.

Pancreatic islet transplantation can replace functional insulin-secreting beta cells for patients with type 1 diabetes. More than 300 patients who have received islet transplantation have returned to a euglycemic condition without using insulin. Therefore, islet transplantation has gained public attention and interest. Unfortunately, shortages in organ donations, suboptional antirejection regimens, and difficulties in islet isolation limit clinical utilization of this therapy. Recently, successful islet transplantation has been reported using a centralized islet isolation facility. The advantage of this experience is that it avoids the high costs in building an isolation facility and maintaining an experienced technical team. However, a private airplane carrier was required for transporting islets back to the transplantation site in a remote hospital. The cost of this specialized transportation was still too high to be considered as a routine procedure. In this study, we report our experience using commercial carriers to deliver isolated human islets from an established isolation facility to a remote medical center.

Animals↗
PubMed2004

Inflammation blockade improves pancreatic islet function.

Pancreatic islet transplantation can replace insulin-secreting beta cells in patients with diabetes mellitus. However, current methodology for isolating islets from a pancreas only retrieves a portion of the total islets. Within these limited number of islets, nearly 50% of beta cells lose biological function before transplantation. Protecting and improving beta-cell viability and function was the goal of this study. Previously we observed that an anti-inflammatory compound, lisofylline (LSF), protects beta cells from cytotoxicity during diabetes development. In this study, we demonstrated that human islets treated in vitro with LSF retained beta-cell glucose responsiveness and insulin secretion in the presence of multiple proinflammatory cytokines. In addition, LSF treatment in vitro enhanced basal insulin production in beta cells, suggesting that LSF can directly improve beta-cell function. LSF reduced beta-cell apoptosis induced by proinflammatory cytokines by 50%. Importantly, 30% fewer LSF-treated islets were sufficient to achieve insulin independence in a murine islet transplantation model. These results demonstrate the ability of LSF-like compounds to protect and enhance beta-cell function, suggesting the potential of using LSF or its analogs in islet transplantation.

Animals↗
PubMed2004

Impact of donor immune cells in pancreatic islet transplantation.

Autoimmune-mediated cytotoxicity may cause pancreatic islet transplant failure, leading to recurrent diabetes. Protection of islet grafts depends on immunosuppressive control, which may also prevent autoimmune recurrence of diabetes. In this study, we compared the survival of syngeneic islet transplants using different strains of donor mice. We observed extended functional survival in the islet grafts from donors lacking the genetic background and potential of autoimmunity. Without immunosuppression, the islet grafts of NOR and immune-deficient NOD. Scid donors functioned up to 3 weeks in syngeneic islet transplants compared to 3-day survivals with the grafts from NOD donors. T-cell proliferation and activation markers, CD44 and CD69, were upregulated in NOD donors, suggesting that T-cell activation had occurred prior to pancreas procurement. Systemic delivery of a recombinant adenoassociated viral vector (AAV) encoding the viral (vIL-10) IL-10 gene (AAV vIL-10) in NOD recipients protected syngeneic islets from autoimmune destruction. Alternatively, pretreatment of NOD donor mice with AAV vIL-10 prolonged islet graft survival in untreated NOD recipients. Both studies indicate the effectiveness of vIL-10 gene therapy in autoimmune regulation. These results suggest that a donor factor may exist in autoimmune-prone donors. Therefore, autoimmune recurrence of diabetes may result from donor immune cells transferred during islet transplantation. The AAV vIL-10 gene therapy suppressed previously activated donor T cells and protected the grafted islets from autoimmune-mediated destruction.

Animals↗