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Biomedical subjects

Li Feng

Publications and source records attributed to Li Feng.

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

Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma.

Mitochondrial DNA (mtDNA) mutations and deletions are frequently observed in cancer, and contribute to altered energy metabolism, increased reactive oxygen species (ROS), and attenuated apoptotic response to anticancer agents. The mechanisms by which cells maintain mitochondrial genomic integrity and the reason why cancer cells exhibit more frequent mtDNA mutations remain unclear. Here, we report that the tumor suppressor molecule p53 has a novel role in maintaining mitochondrial genetic stability through its ability to translocate to mitochondria and interact with mtDNA polymerase gamma (pol gamma) in response to mtDNA damage induced by exogenous and endogenous insults including ROS. The p53 protein physically interacts with mtDNA and pol gamma, and enhances the DNA replication function of pol gamma. Loss of p53 results in a significant increase in mtDNA vulnerability to damage, leading to increased frequency of in vivo mtDNA mutations, which are reversed by stable transfection of wild-type p53. This study provides a mechanistic explanation for the accelerating genetic instability and increased ROS stress in cancer cells associated with loss of p53.

Cell Line, Tumor↗
PubMed2005

Apoptosis in budding yeast caused by defects in initiation of DNA replication.

Apoptosis in metazoans is often accompanied by the destruction of DNA replication initiation proteins, inactivation of checkpoints and activation of cyclin-dependent kinases, which are inhibited by checkpoints that directly or indirectly require initiation proteins. Here we show that, in the budding yeast Saccharomyces cerevisiae, mutations in initiation proteins that attenuate both the initiation of DNA replication and checkpoints also induce features of apoptosis similar to those observed in metazoans. The apoptosis-like phenotype of initiation mutants includes the production of reactive oxygen species (ROS) and activation of the budding-yeast metacaspase Yca1p. In contrast to a recent report that activation of Yca1p only occurs in lysed cells and does not contribute to cell death, we found that, in at least one initiation mutant, Yca1p activation occurs at an early stage of cell death (before cell lysis) and contributes to the lethal effects of the mutation harbored by this strain. Apoptosis in initiation mutants is probably caused by DNA damage associated with the combined effects of insufficient DNA replication forks to completely replicate the genome and defective checkpoints that depend on initiation proteins and/or replication forks to restrain subsequent cell-cycle events until DNA replication is complete. A similar mechanism might underlie the proapoptotic effects associated with the destruction of initiation and checkpoint proteins during apoptosis in mammals, as well as genome instability in initiation mutants of budding yeast.

Apoptosis↗
PubMed2005

Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia.

Cancer cells generally exhibit increased glycolysis for ATP generation (the Warburg effect) due in part to mitochondrial respiration injury and hypoxia, which are frequently associated with resistance to therapeutic agents. Here, we report that inhibition of glycolysis severely depletes ATP in cancer cells, especially in clones of cancer cells with mitochondrial respiration defects, and leads to rapid dephosphorylation of the glycolysis-apoptosis integrating molecule BAD at Ser(112), relocalization of BAX to mitochondria, and massive cell death. Importantly, inhibition of glycolysis effectively kills colon cancer cells and lymphoma cells in a hypoxic environment in which the cancer cells exhibit high glycolytic activity and decreased sensitivity to common anticancer agents. Depletion of ATP by glycolytic inhibition also potently induced apoptosis in multidrug-resistant cells, suggesting that deprivation of cellular energy supply may be an effective way to overcome multidrug resistance. Our study shows a promising therapeutic strategy to effectively kill cancer cells and overcome drug resistance. Because the Warburg effect and hypoxia are frequently seen in human cancers, these findings may have broad clinical implications.

Adenosine Triphosphate↗
PubMed2005

Activation of budding yeast replication origins and suppression of lethal DNA damage effects on origin function by ectopic expression of the co-chaperone protein Mge1.

Initiation of DNA replication in eukaryotes requires the origin recognition complex (ORC) and other proteins that interact with DNA at origins of replication. In budding yeast, the temperature-sensitive orc2-1 mutation alters these interactions in parallel with defects in initiation of DNA replication and in checkpoints that depend on DNA replication forks. Here we show that DNA-damaging drugs modify protein-DNA interactions at budding yeast replication origins in association with lethal effects that are enhanced by the orc2-1 mutation or suppressed by a different mutation in ORC. A dosage suppressor screen identified the budding yeast co-chaperone protein Mge1p as a high copy suppressor of the orc2-1-specific lethal effects of adozelesin, a DNA-alkylating drug. Ectopic expression of Mge1p also suppressed the temperature sensitivity and initiation defect conferred by the orc2-1 mutation. In wild type cells, ectopic expression of Mge1p also suppressed the lethal effects of adozelesin in parallel with the suppression of adozelesin-induced alterations in protein-DNA interactions at origins, stimulation of initiation of DNA replication, and binding of the precursor form of Mge1p to nuclear chromatin. Mge1p is the budding yeast homologue of the Escherichia coli co-chaperone protein GrpE, which stimulates initiation at bacterial origins of replication by promoting interactions of initiator proteins with origin sequences. Our results reveal a novel, proliferation-dependent cytotoxic mechanism for DNA-damaging drugs that involves alterations in the function of initiation proteins and their interactions with DNA.

Antineoplastic Agents, Alkylating↗
PubMed2005

Cerebellopontine angle epidermoids presenting with trigeminal neuralgia.

We studied the clinical characteristics of cerebellopontine angle (CPA) epidermoids presenting with trigeminal neuralgia (TN). Twenty-four patients were analyzed retrospectively and the literature reviewed with regard to clinical manifestation, imaging features, surgical procedures and prognosis. TN may be the initial symptom of CPA epidermoid, particularly in young patients. Epidermoids are characteristically hypodense nonenhancing lesions on CT scans, while on MRI they exhibit long T1 and T2 relaxation times. Although complete removal is ideal in the surgical management of CPA epidermoid, proximity to cranial nerves and the brain stem may pose technical difficulties in complete resection. In addition to complete resection of the tumour, arterial compression at the root entry zone (REZ) of the trigeminal nerve should be sought, and if found, a microvascular decompression (MVD) should be performed. Cranial nerve dysfunction and aseptic meningitis are the most common operative complications.

Adult↗
PubMed2005

Probing lipid-protein interactions using lipid microarrays.

Lipids are central to the regulation and control of several cellular functions. They form many of the important structural features of cells, and are critical members of cellular signal transduction pathways. Cellular dysfunction is often caused by errors in lipid signaling; therefore, the proteins that interact with, synthesize or metabolize the lipids are potential therapeutic targets. Characterizing the contingent of cellular lipids and their abundance and how this is associated with disease will facilitate understanding how to intervene to correct diseases caused by dysfunctional lipid signaling. Since lipid-signaling networks involve several classes of proteins it is essential to determine the identity and role of these proteins in order to understand the networks. These proteins may be receptors, effectors, transporters or enzymes. We present tools, specifically, a lipid microarray platform, to uncover lipid-binding effector proteins that function in lipid signaling pathways. Lipid microarrays will allow researchers to obtain a comparable fingerprint of the proteins from a cell or tissue that bind to lipids, and also enable the identification of functionally important lipid-binding proteins. By applying a systematic approach to the quantification of lipid-protein interactions, lipid microarrays will provide an integrated knowledge base for the human lipidome. These tools have the potential to identify and validate targets to improve personalized medicine and health.

Animals↗
PubMed2005

Isolation of avian infectious bronchitis coronavirus from domestic peafowl (Pavo cristatus) and teal (Anas).

Coronavirus-like viruses, designated peafowl/China/LKQ3/2003 (pf/CH/LKQ3/03) and teal/China/LDT3/2003 (tl/CH/LDT3/03), were isolated from a peafowl and a teal during virological surveillance in Guangdong province, China. Partial genomic sequence analysis showed that these isolates had the S-3-M-5-N gene order that is typical of avian coronaviruses. The spike, membrane and nucleocapsid protein genes of pf/CH/LKQ3/03 had >99 % identity to those of the avian infectious bronchitis coronavirus H120 vaccine strain (Massachusetts serotype) and other Massachusetts serotype isolates. Furthermore, when pf/CH/LKQ3/03 was inoculated experimentally into chickens (specific-pathogen-free), no disease signs were apparent. tl/CH/LDT3/03 had a spike protein gene with 95 % identity to that of a Chinese infectious bronchitis virus (IBV) isolate, although more extensive sequencing revealed the possibility that this strain may have undergone recombination. When inoculated into chickens, tl/CH/LDT3/03 resulted in the death of birds from nephritis. Taken together, this information suggests that pf/CH/LKQ3/03 might be a revertant, attenuated vaccine IBV strain, whereas tl/CH/LDT3/03 is a nephropathogenic field IBV strain, generated through recombination. The replication and non-pathogenic nature of IBV in domestic peafowl and teal under field conditions raises questions as to the role of these hosts as carriers of IBV and the potential that they may have to transmit virus to susceptible chicken populations.

Animals↗
PubMed2005

Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates.

Severe acute respiratory syndrome (SARS) was caused by a novel virus now known as SARS coronavirus (SARS-CoV). The discovery of SARS-CoV-like viruses in masked palm civets (Paguma larvata) raises the possibility that civets play a role in SARS-CoV transmission. To test the susceptibility of civets to experimental infection by different SARS-CoV isolates, 10 civets were inoculated with two human isolates of SARS-CoV, BJ01 (with a 29-nucleotide deletion) and GZ01 (without the 29-nucleotide deletion). All inoculated animals displayed clinical symptoms, such as fever, lethargy, and loss of aggressiveness, and the infection was confirmed by virus isolation, detection of viral genomic RNA, and serum-neutralizing antibodies. Our data show that civets were equally susceptible to SARS-CoV isolates GZ01 and BJ01.

Animals↗
PubMed2005

Hepatoprotective activity of the constituents in Swertia pseudochinensis.

A new xanthone derivative was isolated together with other 13 known constituents from a Chinese natural medicine, Swertia pseudochinensis HARA. Their structures were determined based on the spectral and chemical evidences. Furthermore, respective hexane, ethyl acetate, 1-BuOH, MeOH and water extracts of S. pseudochinensis, and purified compounds were respectively evaluated for their hepatoprotective activities against hepatocyte injury induced by CCl4. All the extracts and isolated compounds exhibited significant hepatoprotective activities at a dose showing no hepatoxicity.

Animals↗
PubMed2005

[Effects of YM injection on oxidative stress injury in renal warm ischemia/reperfusion].

OBJECTIVE: This study was undertaken to determine whether YM injection would attenuate warm I/R injury in mice. METHODS: Renal warm I/R was induced in C57BL/6 males, and the mice were sacrificed 24 hours post-reperfusion. YM was given intraperitoneally 12 hours and 30 min before I/R. The effects of YM on oxidative stress and proinflammatory mediators caused by renal I/R injury were assayed. RESULTS: Renal I/R caused severe injuries in the kidneys of mice. In the presence of YM at doses of 5, 15 and 25 mg/kg, the kidney malondialdehyde (MDA) content reduced by 16.6%, 25.0% and 35.5% respectively, and the kidney superoxide dismutase (SOD) activities were elevated by about 38.7%, 48.3% and 76.1% respectively. ICAM-1 expression was dramatically suppressed in the presence of YM (25 mg/kg). CONCLUSION: YM attenuates the renal warm I/R injury at least partially via decreasing the neutrophils infiltration and suppressing the over-expression of adhesion molecules.

Animals↗
PubMed2005

[Cardioprotective effects of K(ATP) channel opener nicorandil during ischemia/ reperfusion in dogs].

OBJECTIVE: To further confirm the effect of nicorandil in reducing the area of myocardial infarct is through the mediation of activation of the KATP channel but not by its nitrate-like properties, and to determine whether the protective effect is the same or not when the drug is either given immediate after infarction or after reperfusion. METHODS: Thirty-five dogs were randomly divided into five groups as follows. Ischemia/reperfusion (IR) group: the dogs were subjected to 90 minutes of left anterior descending coronary artery(LAD) occlusion followed by 120 minutes reperfusion. Pre-nicorandil (PNIC) group: nicorandil(NIC) 100 microg/kg was administrated by intravenous injection 10 minutes before occlusion, followed by infusion of 10 microg x kg(-1) x min (-1) of the drug till the end of reperfusion. Ischemia nicorandil(INIC) group: NIC 100 microg/kg was administered by intravenous injection 15 minutes after occlusion and 10 microg x kg(-1) x min (-1) of drug intravenously till the end of reperfusion. In the Onset reperfusion treated with nicorandil(RNIC) group: NIC 100 microg/kg was administered intravenously at the onset of reperfusion followed by 10 microg x kg(-1) x min (-1)of drug intravenously up to the end of reperfusion. Glibenclamide(GLIB)+INIC group: before NIC was administered, dogs were pretreated with GLIB 0.3 mg/kg for 10 minutes, and other treatment was the same as INIC group. Hemodynamics data were determined as baseline, 60 minutes post-occlusion, and 120 minutes post-reperfusion. By using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, the infarct areas were analyzed with image analyzer. RESULTS: The results showed that at 60 minutes post-occlusion, cardiac output (CO) was reduced in every group compared with baseline (all P<0.01), CO value recovered at 120 minutes after reperfusion in both PNIC and INIC group (P>0.05). There were no significant differences in heart rate (HR), mean artery pressure(MAP), mean pulmonary artery pressure(MPAP), pulmonary capillary wedge pressure(PCWP) values among all the groups. A marked reduction in the infarct area was found in PNIC group and INIC group (P<0.01) compared with IR group. Administration of GLIB before INIC shows to have no protective effect (P>0.05). CONCLUSION: Our study shows that nicorandil which is a K ATP channel activator, could mimic the effect of ischemic pre-conditioning of the myocardium, by reducing the area of myocardial infarct.

Animals↗
PubMed2004

A new photochromic tetrahydroindolizine.

The title compound, dimethyl 10b'-(4-fluorostyryl)-8',9'-dimethoxy-4-nitro-5',6'-dihydrospiro[9H-fluorene-9,1'(10b'H)-pyrrolo[2,1-a]isoquinoline]-2',3'-dicarboxylate, C38H31FN2O8, is a new photochromic tetrahydroindolizine. One of the C-C bonds at the spiro C atom is very long [1.630 (2) A], thus explaining the photochromic behaviour.

Journal Article↗
PubMed2004

The protective mechanism of Yisheng Injection against hepatic ischemia reperfusion injury in mice.

AIM: Hepatic ischemia/reperfusion injury may cause acute inflammatory, significant organ damage or dysfunction, and remains an important problem for liver transplantation. Our previous in vivo and in vitro studies demonstrated that Yisheng injection (YS), a traditional Chinese medicine, had protective effect on ischemia/reperfusion injury. In this study, we examined whether YS had protective effect for hepatic ischemia/reperfusion injury and explored its protective mechanism. METHODS: Hepatic warm ischemia/reperfusion was induced in mice. YS at different doses (5, 10, 20 mg/kg) was injected intraperitoneally 24 h and 1 h before ischemia and a third dose was injected intravenously just before reperfusion. The hepatocellular injury, oxidative stress, neutrophil recruitment, proinflammatory mediators and adhesion molecules associated with hepatic ischemia/reperfusion injury were assayed by enzyme-linked immunosorbent assay (ELISA), immunohistochemical assay and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Undergoing 90 min of ischemia and 6 h of reperfusion caused dramatical injuries in mouse livers. Administration of YS at doses of 5, 10 and 20 mg/kg effectively reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), from 3 670+/-463 U/L, 2 362+/-323 U/L and 12 752+/-1 455 U/L in I/R group to 1 172+/-257 U/L, 845+/-193 U/L and 2 866+/-427 U/L in YS (20 mg/kg) treated group, respectively (P<0.01). The liver myeloperoxidase (MPO) and malondialdehyde (MDA) contents were decreased from 1.1+/-0.2 (U/mg protein) and 9.1+/-0.7 (nmol/mg protein) in I/R group to 0.4+/-0.1 (U/mg protein) and 5.5+/-0.9 (nmol/mg protein) in YS (20 mg/kg) treated group, respectively (P<0.01). Moreover, the serum levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 55+/-9.9 (pg/mL) in I/R group to 16+/-4.2 (pg/mL) (P<0.01). Furthermore, the over-expressions of TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) were suppressed by YS treatment in a dose-dependent manner. CONCLUSION: YS attenuates hepatic warm ischemia/reperfusion injury by reducing oxidative stress and suppressing the over-expression of proinflammatory mediators and adhesion molecules.

Animals↗
PubMed2004

Expression profiling using a hexamer-based universal microarray.

We describe a transcriptional analysis platform consisting of a universal micro-array system (UMAS) combined with an enzymatic manipulation step that is capable of generating expression profiles from any organism without requiring a priori species-specific knowledge of transcript sequences. The transcriptome is converted to cDNA and processed with restriction endonucleases to generate low-complexity pools (approximately 80-120) of equal length DNA fragments. The resulting material is amplified and detected with the UMAS system, comprising all possible 4,096 (4(6)) DNA hexamers. Ligation to the arrays yields thousands of 14-mer sequence tags. The compendium of signals from all pools in the array-of-universal arrays comprises a full-transcriptome expression profile. The technology was validated by analysis of the galactose response of Saccharomyces cerevisiae, and the resulting profiles showed excellent agreement with the literature and real-time PCR assays. The technology was also used to demonstrate expression profiling from a hybrid organism in a proof-of-concept experiment where a T-cell receptor gene was expressed in yeast.

3' Untranslated Regions↗
PubMed2004

Predicting treatment noncompliance among criminal justice-mandated clients: a theoretical and empirical exploration.

Compliance with therapeutic regimens constitutes an important but infrequently studied precursor of treatment engagement and is a necessary condition of successful treatment. This study builds on recent treatment process research and provides a theory-driven analysis of treatment compliance. Five hypotheses are formulated to predict treatment noncompliance among criminal justice-mandated clients. These hypotheses tap different determinants of treatment progress, including physical prime, supportive social network, conventional social involvement, treatment motivation, and risk-taking propensity. Data from 150 addicted felons participating in a diversion program are analyzed to test the hypotheses. Predictors related to these hypotheses correctly identify 58% of the fully compliant clients and 55-88% of the noncompliant clients. Most hypotheses are at least partially corroborated and a few strong correlates emerge across analyses. Clients in their physical prime, those with poorer social support, and those lacking internal desires for change were found especially likely to violate treatment program rules. Clinical implications are discussed.

Criminal Law↗
PubMed2004

[Treatment performance of submerged membrane bioreactor treating brewery wastewater].

Under the condition of keeping the influent COD: TN: TP = 100:5:1, submerged MBR has an excellent treatment performance for COD and NH4+ -N, and the removals for COD and NH4+ -N are both beyond 90% under steady state, in addition, MBR has a strong adaptation ability for shock organics loading rate. When the organic loading rate was increased from 0.27g/(g x d) to 0.54g/(g x d) suddenly, there was no big fluctuation for COD in effluent. According to the results of GC/MS, the remaining organics in effluent was mainly alkyl hydrocarbon, and the membrane modules played a main role in stabling permeation quality. When the sludge in MBR was at the multiplication stage, the system has a removal of about 40% for TN because of biosynthesis and simultaneous nitrification and de-nitrification, in addition, a certain removal for TP was also observed. When the sludge was at the steady stage, the removal for TN decreased to about 30% due to simultaneous nitrification and de-nitrification, whereas, the removal efficiency for TP was very little, and sometimes even below zero.

Beer↗
PubMed2003

Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism.

Cancer cells are under intrinsic increased oxidative stress and vulnerable to free radical-induced apoptosis. Here, we report a strategy to hinder mitochondrial electron transport and increase superoxide O2. radical generation in human leukemia cells as a novel mechanism to enhance apoptosis induced by anticancer agents. This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I. Partial inhibition of mitochondrial respiration enhances electron leakage from the transport chain, leading to an increase in O2. generation and sensitization of the leukemia cells to anticancer agents whose action involve free radical generation. Using leukemia cells with genetic alterations in mitochondrial DNA and biochemical approaches, we further demonstrated that As2O3, a clinically active anti-leukemia agent, inhibits mitochondrial respiratory function, increases free radical generation, and enhances the activity of another O2.-generating agent against cultured leukemia cells and primary leukemia cells isolated from patients. Our study shows that interfering mitochondrial respiration is a novel mechanism by which As2O3 increases generation of free radicals. This novel mechanism of action provides a biochemical basis for developing new drug combination strategies using As2O3 to enhance the activity of anticancer agents by promoting generation of free radicals.

2-Methoxyestradiol↗