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Biomedical subjects

Nan Li

Publications and source records attributed to Nan Li.

At least 37 records · Page 2Linked to original sources

Crystal structure of AmyA lacks acidic surface and provide insights into protein stability at poly-extreme condition.

Here we report the first crystal structure of a protein, AmyA, a secretory alpha-amylase isolated from Halothermothrix orenii, which is both halophilic and thermophilic. The crystal structure was determined at 1.6 A resolution. AmyA lacks the conserved acidic surface, which is considered essential for protein stability at high salinity. Sedimentation velocity and CD experiments on AmyA reveal the formation of unique reversible poly-dispersed oligomers that show unusually high thermal stability. These studies provide valuable insight into the structural elements that contribute to the stability of AmyA at both physical and chemical extremes and their functional implications.

Acids↗

Frequency of infarct-related artery with myocardial bridging in patients with ST-elevation myocardial infarction and its impact upon percutaneous coronary intervention.

BACKGROUND: Myocardial bridging (MB) as a congenital condition with a reported frequency of 5% - 12% in diagnostic coronary angiography may be an important factor causing myocardial ischemia. However, its frequency in the infarct-related artery (IRA) of patients with ST-elevation myocardial infarction (STEMI) and the impact upon percutaneous coronary intervention (PCI) remain undetermined. In this study, we investigated MB frequency and its impact upon primary PCI in patients with STEMI. METHODS: The data of coronary angiography for 554 consecutive patients with STEMI who had undergone successful primary PCI were retrospectively analyzed to identify a frequency of MB in the IRA and its association with gender and age. According to the angiographic findings, the patients were divided into MB patients and non-MB patients. The endpoints of this study included immediate angiographic findings after primary PCI and 6-month major adverse cardiac events (MACE) (death, recurrent myocardial infarction, target lesion or vessel revascularization) between the MB patients and the non-MB patients. RESULTS: A frequency of MB in the IRA of 46 patients (8.3%) was identified in this series; it was more common in patients > or = 65 years old (36/206) than in those < 65 years old (10/348) (17.5% vs 2.9%, P < 0.001). The trend of MB in the IRA was observed more frequently in women without significant difference than in men (10.2% vs 7.8%). TIMI grade III flow was achieved in 91.9% (509/554) of all patients following primary PCI, in 60.9% (28/46) of the MB patients and in 94.7% (481/508) of the non-MB patients respectively (P < 0.001). The in-hospital mortality was 4.7% (26/554) in this series including 13.0% (6/46) of the MB patients and 3.9% (20/508) of the non-MB patients (P < 0.001). A significant difference in 6 months MACE was seen between the MB patients (19%) and the non-MB patients (6.2%) (P < 0.001). CONCLUSIONS: MB in the IRA is relatively common in elderly patients with STEMI with a more evident trend in women, suggesting that arteriosclerosis and plaque rupture occurs more easily in the proximal artery to MB than in younger patients. Poor TIMI grade flow in patients with MB in the IRA after primary PCI may contribute to a high in-hospital mortality rate (13%) and 6-month MACE (19%) in the MB patients.

Adult↗

A novel CFTR mutation found in a Chinese patient with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is rare in Chinese. We investigated the mutations in the gene of cystic fibrosis transmembrane conductance regulator (CFTR) in a Chinese CF patient and reviewed the clinical features, gene mutations in Chinese CF cases. METHODS: Blood samples were collected from a previously reported CF girl and her parents. The 24 coding exons of CFTR of the proband were amplified and sequenced. RESULTS: A Chinese girl of 16 years old was diagnosed as CF at the age of 14. She had recurrent productive cough with bronchiectasis in bilateral upper lobes, parasinusitis and otitis media, but without pancreatic involvement. Her sweat chloride was (108.9 +/- 3.3) mmol/L. A heterozygous novel missense mutation of 699 C --> A which results in the amino acid change of N189K was identified in exon 5. In addition, a heterozygous 3821 - 3823 delT mutation in exon 19 was found in CFTR. The mutation 699C --> A was inherited from her father, and the 3821 - 3823 delT mutation was from her mother. Twenty patients with CF in Chinese reported from 1974 to 2004 were also reviewed. DelF508 mutation was not found in the nine cases whose CFTR mutations were analyzed. CONCLUSIONS: The CF proband carries two heterozygous mutations (699C --> A and 3821 - 3823 delT) in CFTR. 699C --> A mutation is a novel mutation which is not reported previously. Review of reported Chinese cases suggests that the genotype of Chinese CF may be different from those of white cases. More studies are needed to understand the spectra of CFTR and clinical CF features in Chinese.

Adolescent↗

Lactobacillus rhamnosus GG decreases lipopolysaccharide-induced systemic inflammation in a gastrostomy-fed infant rat model.

OBJECTIVES: A gastrostomy-fed rat infant "pup-in-a-cup" model was used to test the hypothesis that enterally administered Lactobacillus rhamnosus GG (LGG) decreases the proinflammatory response induced by Escherichia coli lipopolysaccharide (LPS) in the developing infant rat small intestine, plasma, lung and liver. METHODS: Two groups of 6- to 7-day-old pups were fed a rat milk substitute with LPS added via the gastrostomy tube for 6 days. One of the rat milk substitute-fed groups received supplemental LGG; another group received LPS without LGG. Age-matched mother-fed rat pups were used as controls. RESULTS: LPS treatment blunted body growth, but LGG supplementation had no effect on weight increments. LGG decreased LPS-induced inflammation in intestinal tissue; CINC-1 (rodent IL-8 equivalent) production in plasma, liver, lung and distal small intestine; and tumor necrosis factor alpha (TNF-alpha) production in plasma and lung. Cytokine multiplex assay showed lung interleukin (IL)-1beta, IL-6, IL-10, IL-18, growth-related oncogene (GRO)/KC (rat CINC-1) and TNF-alpha were significantly higher in gastrostomy-fed, LPS-treated pups than in mother-reared pups, and LGG significantly blunted the LPS-induced elevation of IL-1beta, IL-10, IL-18, GRO/KC and TNF-alpha; liver GRO/KC was significantly higher in gastrostomy-fed, LPS-treated pups than in mother-reared pups, and LGG significantly blunted the LPS-induced elevation of GRO/KC. CONCLUSIONS: LGG provided by the enteral route is able to downregulate LPS-induced proinflammatory mediators. This effect is not only present in the splanchnic organs, that is, the intestine and the liver, but extends to the plasma and a distal organ, the lung.

Animals↗

Histopathological study of vascular changes after intra-arterial and intravenous injection of N-butyl-2-cyanoacrylate.

OBJECTIVE: To assess the histopathological vascular changes after injection of N-butyl-2-cyanoacrylate into the vessels of adult rabbits. METHODS: The animals used were 42 pure-blood New Zealand white rabbits weighing 2-3 kg. 0.2 mL cyanoacrylate with lipiodol was injected into the external jugular vein and femoral artery of each rabbit. Tissue specimens were obtained for histopathological study at 3 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months and 3 months after injection. RESULTS: The vessels were obliterated immediately after the injection. The main manifestation of histopathology at 3 days to 2 weeks was an acute inflammatory reaction; this progressed to subacute vasculitis at 3 weeks and a chronic granulomatous foreign body reaction developed at 4 weeks. The glue mass essentially disappeared in 2-3 months, replaced by fibrotic tissue with partial vascular recanalization. At 3 weeks after injection, the elastic fibrils of the arterial wall proliferated distinctly, resulting in narrowing of the lumen with subsequent obliteration, whereas the venous wall still showed inflammation and necrosis without hyperplasia of elastic fibrils. Extrusion of glue was observed over 1-3 months in both arteries and veins and was obvious in the latter. CONCLUSIONS: The histopathological changes after injection of N-butyl-2-cyanoacrylate were similar in the arteries and the veins with the exception of hyperplasia of elastic fibrils in the arterial wall and inflammation and necrosis in the venous wall at 2-3 weeks. Glue extrusion was seen in both arteries and veins.

Animals↗

The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.

PURPOSE: Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS: The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by real-time RT-PCR. RESULTS: Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82%+/-7% (P<0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64%+/-9% (P<0.001). CONCLUSIONS: Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP.

Angiogenesis Inhibitors↗

Brain natriuretic peptide: a potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

Adult↗

[Distribution of STR locus DXS8027 polymorphism in the Han population in Qinba mountain areas].

To investigate the genetic polymorphism at DXS8027 STR locus for Han population in Qinba Mountain Areas and construct a preliminary population genetics database for this locus. We collected 550 venous blood samples from unrelated Han individuals of the Qinba Mountain Areas, Blood was treated with anticoagulant EDTA, and genomic DNA was obtained by phenol-chloroform extraction. Target fragments for the DXS8027 were amplified by PCR, separated on 8% non-denaturing polyacrylamide gel. electrophoresis and stained with 0.1% silver nitrate (AgNO3). Nine alleles were observed among the total samples, and the allele frequencies were in accordance with Hardy-Weinberg equilibrium (P>0.05) with relatively high heterozygosity (Het=0.7968). The results showed that there was a significant difference in the distribution of DXS8027 allele frequency between males and females (Chi 2=30.242, P<0.01), but the difference was not significant in the same gender groups of the two areas (Chi 2=4.703, P >0.05; Chi 2=14.952, P >0.05), or between the two areas regardless of gender (Chi 2=15.2, P >0.05). There was a very significant difference in DXS8027 allele frequency in populations of the Qinba Mountain Areas and the European populations, (Chi 2=37.572, P<0.01). It provides database to further study this STR locus in different population.

Asian People↗

[Effects of routine early amniotomy on labor and health status of foetus and neonate: a meta-analysis].

OBJECTIVE: To analyze the effects of routine early amniotomy on labor and health status of foetus and neonate. METHODS: The results of Early amniotomy increases the frequency of fetal heart rate abnormalities, A randomized controlled trial of early amniotomy, Effect of early amniotomy on the risk of dystocia in nulliparous women, The influence of elective amniotomy on fetal heart rate patterns and the course of labor in term patients: A randomized study, Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term and A randomized controlled trial and meta-analysis of active management of labour were analyzed using Mantel-Haenszel method (fixed effect model) in meta-analysis. RESULTS: (1) The routine early amniotomy can shorten 94.90 min of the first stage of labor, 95% CI (-119.17, -70.52). (2) The OR for cesarean section was 1.25, 95% CI (0.99-1.57), for instrumental vaginal delivery was 1.05, 95% CI (0.90-1.24). (3) There was no difference in abnormal fetal heart rate at first stage (OR = 0.95, 95% CI: 0.75-1.21), but there was increased abnormal fetal heart rate at second stage (OR = 1.28, 95% CI: 1.02-1.61). (4) The frequency of stained amniotic fluid and abnormal Apgar scores at 1 minute was not different significantly [OR = 1.17, 95% CI (0.78-1.73); OR = 0.71, 95% CI: (0.49-1.03)]. CONCLUSIONS: Routine early amniotomy appears to be associated with both benefits and risks. Beneficial effects include reductions in labor duration and possible decrease in frequency of abnormal Apgar score at one minute. Risks include increase in abnormal fetal heart rate at second stage and possible rise in cesarean section rate.

Amnion↗

[Cloning of F gene of Newcastle disease virus HeB02 isolate and the study of its DNA vaccine].

In order to amplify F gene of NDV HeB02 strain, one pair of primers was designed according to the GenBank sequence, and a 1.66 kb F gene fragment was obtained by RT-PCR. Sequence analysis indicated that the homologies of the nucleotide sequence of HeB02 strain to those of F48 E9, La Sota and Clone30 strains were 88.1%, 84.9% and 83.8% respectively. The expression plasmid pSV-F was constructed by inserting the F gene into the pVAX1 vector, and transfected into the cultured COS 7 cell line via liposomes. The specific 5.9 kD protein was detected by SDS-PAGE and the immunogenicity of the expressed F protein was confirmed by Western blot, ELISA and neutralization test. 3 week-old SPF chickens were subcutaneously immunized twice at week 0 and 3 with 50 microg DNA of plasmid pSV-F by electroporration. 5 weeks later, all chickenss were challenged with 100 x EID50 of NDV HeB02 strain, 1 week post challenge all chickenss were sampled by larynx swabbing to isolate virus and the HI level of NDV was measured. The results indicated that the virus isolation was negtive in all vaccinated chickenss and positive in all control chickens. The HI titres reached to 8.3log2 +/- 1.30 and 7.2log2 +/- 1.23 induced by NDV vaccine and positive cells (pSV-F), respectivily, the HI titres induced by Control cells (pVAX1) was not detected. Furthermore, the HI titres reached to 9.8log2 +/- 1.55 and 8.9log2 +/- 1.77 in vaccinated group with NDV vaccine and positive cells (pSV-F), respectivily, were sinificantly higher than that of the control cells (pVAX1) immunized group( HI titers was 3.0 log2 +/- 1.40, P < 0.01) after challenge. These results showed that the plasmid pSV-F could be as a candidate of DNA vaccine to provide protective immune response against NDV infection.

Animals↗

Anti-apoptotic hPEBP4 silencing promotes TRAIL-induced apoptosis of human ovarian cancer cells by activating ERK and JNK pathways.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cell lines but not typically in normal or nontransformed cells, which makes TRAIL a desirable therapeutic agent to fight cancer. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a recently identified anti-apoptotic molecule and has been shown to be highly expressed in breast and ovarian cancer cells. We demonstrate that silencing of hPEBP4 in CaoV-3 ovarian cancer cells potentiates TRAIL-induced apoptosis. We found that endogenous hPEBP4 interacts with Raf-1 and MEK1 in TRAIL-treated CaoV-3 cells by co-immunoprecipitation analysis. Simultaneously, silencing of hPEBP4 in CaoV-3 cells enhances TRAIL-induced ERK and JNK activation. Moreover, the inhibitors of MEK1 or JNK can reduce hPEBP4-silence-induced TRAIL sensitivity. Therefore, silencing of hPEBP4 in CaoV-3 ovarian cancer promotes TRAIL-induced apoptosis, and the increased MAPK activation is required for the apoptosis sensitization. All these data indicate that silencing of hPEBP4, an important potential target, may be a promising approach for the treatment of ovarian cancer.

Apoptosis↗

[Study on polymorphic Hind III restriction site of the Y chromosome and essential hypertension in Tangshan district].

OBJECTIVE: Since males are at higher risk of cardiovascular diseases than females, the aim of the study was to examine whether there is an association between BP and a polymorphic Hind III biallelic marker in nonrecombining region of Y chromosome in essential hypertension in Tangshan district in China. METHODS: In the study, 225 patients with essential hypertension and 187 healthy people were enrolled into this study as control group. DNA was extracted from white blood cell. Segments of polymorphic Hind III restriction site of the Y chromosome were amplified from DNA by polymerase chain reaction (PCR). PCR products were restricted with 10 U of Hind III for a night at 37 degrees C. The digested products were subjected to electrophoresis in 3% agarose gels, and stained with ethidium bromide. RESULTS: We amplified 178 controls (95.2%) and 216 essential hypertensive patients (96.0%) successfully. Hind III(-) genotype was found in 45.8% of the men in essential hypertension and in 32.0% of the men in the controlled group. The Hind III(-) genotype was significantly higher than that in the controls (chi2 = 7.782, P = 0.007). However, the Hind III(+) genotype was lower in SBP (133.16 mm Hg +/- 21.60 mm Hg vs. 143.58 mm Hg +/- 24.16 mm Hg, P < 0.001), DBP (82.82 mm Hg +/- 11.72 mm Hg vs. 86.82 mm Hg +/- 12.65 mm Hg, P = 0.001), pulse pressure (50.34 mm Hg +/- 14.31 mm Hg vs. 56.76 mm Hg +/- 14.20 mm Hg, P < 0.001) and mean arterial pressure (99.59 mm Hg +/- 14.19 mm Hg vs. 105.74 mm Hg +/- 15.31 mm Hg, P < 0.001) than the Hind III(-) genotype. CONCLUSION: Polymorphic Hind III restriction site of the Y chromosome seemed to be associated with essential hypertension in Tangshan district in China.

Case-Control Studies↗

[Screening of microorganism producing polyunsaturated fatty acids with sugarcane molasses].

A strain name LB1 producing polyunsaturated fatty acids with sugarcane molasses was screened form soil samples by the methods of Sudan Black B stain and the determination of PUFAs' iodine value. Based on the grass morphological and physiological characteristics and the sequence similarity of ribosomal DNA-ITS, the strain was identified as Mucor recurvus sp.. The results of L64 (4(3)) orthogonal experiments indicated when Mucor recurvus was cultivated at 28 degrees C for 5 days with 160 r/min, the yields of PUFAs with 10(0) BX sugarcane molasses (pH 6.0) were up to 80.49% content of total fatty acids. The total lipids content was 57.08% of fermentation biomass, which were composed of 15.42% Oleic acid, 14.38% Linolenic, 23.55% gamma-Linolenic, 3.06% alpha-Linolenic, 9.87% Arachidonic acid, 8.14% Eicosapentaenoic acid, 6.07% Docosahexaenoic acid, etc.

Chromatography, Gas↗

Primary hepatic malignant fibrous histiocytoma mimicking cystadenocarcinoma: a case report.

BACKGROUND: Malignant fibrous histiocytoma is the most common sarcoma of soft tissue, which occurs usually in the extremities, but less common in the retroperitoneal space, abdominal cavity or other sites. Primary malignant fibrous histiocytoma of the liver is extremely rare; only 28 cases have been reported to date in the English literature. METHODS: In this report, a case of primary malignant fibrous histiocytoma of the liver was described in terms of clinical presentations, diagnosis and treatment and outcome. RESULTS: A 50-year-old man had a large multicystic-mass lesion in the left lobe of the liver, which was inoperable by laparotomy. Pathological examination of biopsy specimen after operation confirmed a malignant fibrous histiocytoma of storiform-pleomorphic type. The tumor developed rapidly, and the patient died of hepatic failure 2 months after the surgery. CONCLUSIONS: Primary malignant fibrous histiocytoma of the liver is diagnosed in late stage because of its rarity and non-specific presentations. Surgical resection, if feasible, is the first step treatment. The prognosis of primary malignant fibrous histiocytoma of the liver is grim with a median survival of 3 months as reported. Surgeons should be alert to the existence of this type of soft tissue tumor in the liver.

Cystadenocarcinoma↗

[Reconstruction of bone defects with autograft after resection of upper extremity bone].

OBJECTIVE: To discuss the reconstructive method of the bone defect after resection of the upper extremity bone tumor and to assess the outcome of the autograft to reconstruct the bone defect after the bone tumor resection. METHODS: From August 1998 to March 2004, 16 patients aged 7-45 years suffering from bone tumor of the upper extremity were treated with the wide resection of the bone tumor and the reconstruction of the bone defect by the autograft. The following diagnoses were confirmed by pathological examination: Ewing's sarcoma and osteosarcoma of the proximal humerus in 1 patient each; Ewing's sarcoma of the distal humerus in 2 patients; giant cell tumor in 8 patients, high-grade chondrosarcoma in 2, malignant fibrohistiocytoma in 1; and osteosarcoma in 1 of the distal radius. Substitution of the proximal humerus with the clavicle was performed in 2 patients, and the distal humerus with the fibula in other 2 patients. Of the 12 patients with tumor in the distal radius, 1 was reconstructed with autograft of the iliac bone and 11 with autograft with the fibula. The functional outcome was evaluated by the MSTS score. RESULTS: The follow-up for 36 and 12 months respectively revealed that in the 2 patients undergoing the autograft with the clavicle in the proximal humerus, good shoulder functions of flexion and extension were obtained although the function of abduction was poor, with the MSTS scores of 23 and 22 respectively. In the 2 patients undergoing the autograft with the fibular in the distal humerus, good elbow function and bone union were observed according to the follow-up for 3 and 4 months respectively, with the MSTS scores of 24 and 19 respectively. Of the 12 patients undergoing the autograft in the distal radius, 11 had an excellent or good function with no complication, with the average MSTS score of 22.6 (ranging from 18 to 27), according to the follow-up for 6-75 months; only 1 had no bone union 10 months after operation and lost the follow-up afterwards. CONCLUSION: Reconstruction of the bone defect with the autograft after the wide resection of the upper extremity bone tumor is an ideal and reliable method for some suitable patients, especially for some children.

Adolescent↗

Enhanced and selective adsorption of mercury ions on chitosan beads grafted with polyacrylamide via surface-initiated atom transfer radical polymerization.

Enhanced and selective removal of mercury ions was achieved with chitosan beads grafted with polyacrylamide (chitosan-g-polyacrylamide) via surface-initiated atom transfer radical polymerization (ATRP). The chitosan-g-polyacrylamide beads were found to have significantly greater adsorption capacities and faster adsorption kinetics for mercury ions than the chitosan beads. At pH 4 and with initial mercury concentrations of 10-200 mg/L, the chitosan-g-polyacrylamide beads can achieve a maximum adsorption capacity of up to 322.6 mg/g (in comparison with 181.8 mg/g for the chitosan beads) and displayed a short adsorption equilibrium time of less than 60 min (compared to more than 15 h for the chitosan beads). Coadsorption experiments with both mercury and lead ions showed that the chitosan-g-polyacrylamide beads had excellent selectivity in the adsorption of mercury ions over lead ions at pH < 6, in contrast to the chitosan beads, which did not show clear selectivity for either of the two metal species. Mechanism study suggested that the enhanced mercury adsorption was due to the many amide groups grafted onto the surfaces of the beads, and the selectivity in mercury adsorption can be attributed to the ability of mercury ions to form covalent bonds with the amide. It was found that adsorbed mercury ions on the chitosan-g-polyacrylamide beads can be effectively desorbed in a perchloric acid solution, and the regenerated beads can be reused almost without any loss of adsorption capacity.

Adsorption↗

Reagentless biosensor for phenolic compounds based on tyrosinase entrapped within gelatine film.

A simple and new reagentless phenolic compound biosensor was constructed with tyrosinase immobilized in the gelatine matrix cross-linked with formaldehyde. The morphologies of gelatine and gelatine/tryosinase were characterized by SEM. The tyrosinase retains its bioactivity when being immobilized by the gelatine film. Phenolic compounds were determined by the direct reduction of biocatalytically liberated quinone at -0.1 V vs SCE. The process parameters for the fabrication of the enzyme electrode were studied. Optimization of the experimental parameters has been performed with regard to pH, operating potential, temperature and storage stability. This biosensor exhibits a fast amperometric response to phenolic compounds. The linear range for catechol, phenol, and p-Cresol determination was from 5 x 10(-8) to 1.4 x 10(-4) M, 5 x 10(-8) to 7.1 x 10(-5)M, and 1 x 10(-7) to 3.6 x 10(-5)M, with a detection limit of 2.1 x 10(-8) M, 1.5 x 10(-8) M, and 7.1 x 10(-8 )M, respectively. The enzyme electrode retained ca.77% of its activity after 7 days of storage at 4 degrees C in a dry state. The proposed sensor presented good repeatability, evaluated in terms of relative standard deviation (R.S.D.=8.6%) for eight different biosensors and was applied for determination in water sample. The recovery for the sample was from 99.0% to 99.8%.

Benzoquinones↗

Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest.

PURPOSE: The current therapeutic approach is not so effective in breast cancer patients. Alternative treatment protocols aimed at different targets need to be explored. We recently reported a novel phosphatidylethanolamine-binding protein, human phosphatidylethanolamine-binding protein 4 (hPEBP4), as an antiapoptotic molecule. The finding led us to explore a promising approach for breast cancer therapy via silencing the expression of hPEBP4. EXPERIMENTAL DESIGN: hPEBP4 expression in clinical breast specimens was examined by Tissue Microarrays. RNA interference was used to silence hPEBP4 expression in MCF-7 breast carcinoma cells and the effects on cell proliferation, cell cycle progression, apoptosis, as well as underlying mechanisms, were investigated. RESULTS: hPEBP4 was found to be expressed in up to 50% of breast cancers but in only <4% of normal breast tissues. Silencing of hPEBP4 potentiated tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis and cell cycle arrest in MCF-7 cells, which was due to the increased mitogen-activated protein kinase activation and the enhanced phosphatidylethanolamine externalization. Further investigation showed that silencing of hPEBP4 in MCF-7 cells promoted TNF-alpha-induced stability of p53, up-regulation of phospho-p53ser15, p21waf/cip, and Bax, and down-regulation of Bcl-2 and Bcl-xL, which were shown to depend on extracellular signal-regulated kinase 1/2 and c-jun NH2-terminal kinase activation by hPEBP4 silencing. Moreover, the increased proportion of cells in the G0-G1 phase of cell cycle was observed in hPEBP4-silenced MCF-7 cells on TNF-alpha treatment and the expression of cyclin A and cyclin E was down-regulated more significantly. CONCLUSIONS: The antiapoptotic effect and the preferential expression pattern in breast cancer tissues make hPEBP4 a new target for breast cancer therapy. Silencing of hPEBP4 expression may be a promising approach for the treatment of breast carcinoma.

Apoptosis↗