Flexible wurtzite-type ZnS nanobelts with quantum-size effects: a diethylenetriamine-assisted solvothermal approach.
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DEET↗
Biomedical subjects
Jing Li
Publications and source records attributed to Jing Li.
Study on the therapeutic mechanism of the active principle of the Chinese drug Paeoniae Radix 801 through affinity biosensors IAsys plus quartz crystal microbalance.
OBJECTIVE: To study the targeted point and mechanism of the function of the blood-activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its cardiovascular protective effects and its specific binding with endothelin 1 (ET-1) as well as the dynamics of the two's interactive function by means of using affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM). METHODS: ET-1 was immobilized on the surfaces of IAQCM by using the new surface modification methods. The PR801 in the solution was detected by modified substrates and the specific binding between PR801 and ET-1 was studied. RESULTS: The curves went up or down after adding PR801. There is specific binding between PR801 and ET-1. The bound mass were 0.458 ng/mm(2) and 133.54 ng/cm(2), respectively. There exists relatively good stability with these two methods. CONCLUSION: The affinity biosensors: IAQCM can be used to study the interaction mechanism between PR801 and ET-1, providing a new way to study the interaction mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore, ET-1 is another target that PR801 can bind specifically besides thromboxane A(2).
Biosensing Techniques↗
Tra2alpha promotes RA induced neural differentiation of P19 cells.
The present study demonstrates a high level of the nuclear Transformer 2alpha (Tra2alpha) protein in adult mouse brain relative to other tissues, including muscle, heart, liver, lungs, kidney and small intestine, suggesting the potential importance of Tra2alpha in neural function. The level of Tra2alpha in mouse cerebrum is developmentally regulated, peaking at neonate stage. In P19 carcinoma cells, Tra2alpha is transiently up-regulated upon retinoic acid (RA) treatment. Although over-expression of Tra2alpha protein alone does not elicit P19 differentiation, under these conditions the response of P19 cells to RA is significantly increased. The results suggest that Tra2alpha proteins may act as a mediator in the signal pathway associated with RA-induced differentiation in P19 cells.
Animals↗
Significant intestinal excretion, one source of variability in pharmacokinetics of COL-3, a chemically modified tetracycline.
PURPOSE: This study was undertaken to examine the disposition of COL-3, a chemically modified tetracycline, in order to elucidate its major route of elimination as one possible source of the variability in pharmacokinetics of COL-3 in vivo. METHODS: The disposition profile of COL-3 in vivo was assessed by examining the urinary and fecal excretion of the unchanged drug and/or its metabolites in rats after single intravenous and oral administration. The biliary excretion of COL-3 administered orally in bile duct-cannulated rats was also examined. In addition, plasma protein binding and cytochromes P450-mediated metabolism were explored along with erythrocyte partitioning in vivo. Furthermore, transport of COL-3 across Caco-2 monolayers was performed to elucidate the mechanism of intestinal excretion of COL-3 in vivo. RESULTS: COL-3 was extensively bound to plasma protein in rat (98%) and human plasma (95%). The affinity of rat blood cells for COL-3, as measured by the ratio of drug concentration in blood cells to that unbound in plasma, was about 36. Of the single intravenous and oral doses, less than 0.2% and 0.03% were excreted unchanged in rat urine, respectively; while 32.1 +/- 9.9% and 38.8 +/- 6.1% were recovered unchanged in rat feces, respectively, within 48 h postdosing. Of the oral dose, 1.36 +/- 0.66% and 2.97 +/- 0.88% were excreted in rat bile as the unchanged COL-3 and the total of COL-3 and its glucuronide conjugate, respectively, within 24 h after dosing. COL-3 had insignificant cytochrome P450-mediated metabolism but underwent phase II metabolism (i.e., glucuronidation) in a minor quantity. COL-3 was not a substrate of P-glycoprotein. Its transport across Caco-2 monolayers was significantly affected by protein binding and pH. CONCLUSIONS: Intestinal excretion, a route different from biliary excretion, is the major route of elimination for COL-3 in rats. Variability in intestinal excretion, due to extreme variable intestinal contents (food and digestive fluids), could be one source of variability in COL-3 pharmacokinetics in vivo in addition to the dissolution rate-limited absorption.
Animals↗
Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia.
OBJECTIVE: Does the use of nifedipine and magnesium sulfate together increase serious magnesium-related effects? STUDY DESIGN: This was a retrospective chart review of women who were admitted to BC Women's Hospital and Health Centre (1997-2001) and were given intravenous magnesium sulfate for preeclampsia. Serious magnesium-related effects were compared among 162 cases who received magnesium sulfate and contemporaneous nifedipine and 215 control subjects who received magnesium sulfate and either another antihypertensive (n=32 women) or no antihypertensive (n=183 women) medication. Chi-squared test, Fisher's exact test, or the Student t test was used for data comparison between cases and each control group. A probability value of <.05 was considered statistically significant. RESULTS: The cases had more severe preeclampsia and a longer magnesium sulfate infusion. However, cases had no excess of neuromuscular weakness (53.1%) versus control subjects who received antihypertensive medication (53.1%; P=.99) or control subjects who received no antihypertensive medication (44.8%; P=.13) or other serious magnesium-related effects. Cases versus control subjects who received antihypertensive medication had less neuromuscular blockade (odds ratio, 0.04; 95% CI, 0.002-0.80). Cases versus control subjects who received no antihypertensive medication had less maternal hypotension (41.4% vs 53.0%; P=.04). CONCLUSION: The use of nifedipine and magnesium sulfate together does not increase the risk of serious magnesium-related effects.
Adult↗
Characterization of conformational epitope of alginate-derived polymannuronates by surface plasmon resonance.
In the present study, we developed a mAb to alginate-derived polymannuronates (ADPM) and examined the antigenic epitopes using surface plasmon resonance (SPR) in conjunction with a large panel of oligomannuronate probes. We found that tetrasaccharide is the minimum-binding unit, and that increases in chain length from the tetrasaccharide to the heptsaccharide further enhance monovalent binding. A sharp increase in affinity was observed when increasing from the octasaccharide to the cosasaccharide, which is due to a further enhancement of the individual antigenic epitope combined with multivalency. Kinetic binding studies further suggested that the conformational epitope is discontinuous and infrequent and that a C6-carboxyl group is important in maintaining the conformational epitope. Moreover, CD analysis revealed there were conformational structures in epitopes. The data support our hypothesis that the conformational epitope for the mAb may be an extended helical segment of ADPM. ADPM exists mainly in linear form, but it can infrequently and spontaneously form extended helices. Although helices are not prevalent in ADPM, the immune system preferentially selects these conformational epitopes because they are unique. Together, our results indicate that the antigenic epitopes in beta-d-mannuronates are conformational and require C6-carboxyl groups.
Alginates↗
Relationship of systemic exposure to unbound docetaxel and neutropenia.
OBJECTIVE: Our objective was to evaluate the association between exposure to unbound docetaxel and neutropenia in patients with cancer and to identify factors influencing unbound docetaxel clearance. METHODS: Docetaxel was administered once every 3 weeks at a dose of 75 mg/m 2 to 49 patients with normal liver function (n = 40, group 1) or mild elevations in liver function test results (n = 9, group 2) or at a dose of 50 mg/m2 to patients with moderate elevations in liver function test results (n = 6, group 3). Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy. Total docetaxel concentrations were determined by HPLC and tandem mass spectrometry, and unbound docetaxel fraction was determined by equilibrium dialysis. RESULTS: In patients with normal liver function, unbound docetaxel disposition was characterized by mean (+/-SD) maximum plasma concentration (C max), area under the curve (AUC), and clearance values of 233 +/- 101 ng/mL, 32 +/- 143 ng/mL . h, and 565 +/- 329 L/h, respectively. Unbound clearance varied 8.5-fold; polysorbate 80 exhibited mean (+/-SD) C max , AUC, and clearance values of 451 +/- 221 microg/mL, 528 +/- 217 microg/mL . h, and 8.18 +/- 3.66 L/h, respectively; and clearance varied 6.7-fold. Unbound docetaxel clearance was reduced in patients with moderate liver impairment (groups 1 and 2 versus group 3, P = .020). From multiple linear regression analysis, only polysorbate 80 AUC and liver impairment were significantly associated with unbound docetaxel clearance. Both unbound docetaxel AUC and total AUC were correlated with the percentage decrements in absolute neutrophil count (P = .002 and P = .029, respectively), as well as the worst grade of neutropenia (P = .013 and P = .220, respectively), where higher exposure was associated with worse hematologic toxicity. CONCLUSIONS: Exposure to unbound docetaxel is closely related to drug-induced hematologic toxicity and should be considered in future pharmacologic investigations.
Adult↗
A geraniol-synthase gene from Cinnamomum tenuipilum.
Geraniol may accumulate up to 86-98% of the leaf essential oils in geraniol chemotypes of the evergreen camphor tree Cinnamomum tenuipilum. A similarity-based cloning strategy yielded a cDNA clone that appeared to encode a terpene synthase and which could be phylogenetically grouped within the angiosperm monoterpene synthase/subfamily. After its expression in Escherichia coli and enzyme assay with prenyl diphosphates as substrates, the enzyme encoded by the putative C. tenuipilum monoterpene synthase gene was shown to specifically convert geranyl diphosphate to geraniol as a single product by GC-MS analysis. Biochemical characterization of the partially purified recombinant protein revealed a strong dependency for Mg2+ and Mn2+, and an apparent Michaelis constant of 55.8 microM for geranyl diphosphate. Thus, a new member of the monoterpene synthase family was identified and designated as CtGES. The genome contains a single copy of CtGES gene. Expression of CtGES was exclusively observed in the geraniol chemotype of C. tenuipilum. Furthermore, in situ hybridization analysis demonstrated that CtGES mRNA was localized in the oil cells of the leaves.
Acyclic Monoterpenes↗
Effects of vacuum-assisted closure on wound microcirculation: an experimental study.
OBJECTIVE: To study the mechanism through which vacuum-assisted closure (VAC) induces an increase in blood flow and reduces oedema on skin wounds. METHODS: Thirty-two Japanese large-ear white rabbits were used. A round full-thickness skin defect (retaining the perichondrium), 2 cm in diameter, was created on each dorsal ear. The wound on the left ear was assigned to the experimental group, and the wound on the right ear to the control group. In the experimental group, the sterile foam dressing was trimmed to the appropriate size and geometry for the given wound and placed into the wound defect. The surface of the wound containing the foam dressing was covered with an adhesive drape to create an airtight seal. Afterwards, negative pressures of -5, -10, -15 and -20 kPa were exerted on the same wound, each lasting for 20 minutes, at intervals of 10 minutes. In the control group, the wound was treated with petrolatum gauze only. At different time points, the microcirculation microscope and image pattern analysis were used to observe the variation in wound microcirculation through a detective window. RESULTS: It was found that VAC promoted capillary blood flow velocity, increased capillary calibre and blood volume, stimulated endothelial proliferation and angiogenesis, narrowed endothelial spaces, and restored the integrity of the capillary basement membrane. CONCLUSION: By increasing capillary calibre and blood volume and by stimulating angiogenesis, VAC could improve blood circulation in wounds. By narrowing endothelial spaces and by restoring the integrity of capillary basement membranes, VAC could decrease the permeability of blood vessels and wound oedema.
Animals↗
The marine bromotyrosine derivatives.
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Alkaloids↗
Analysis of differential gene expression patterns in colon cancer and cancer stroma using microdissected tissues.
BACKGROUND AND AIMS: The surrounding cancer stroma is increasingly recognized as playing an important role in cancer proliferation, invasion, and metastasis. Here, we analyzed patterns of gene expression in colon cancer cells, surrounding stroma, and normal mucosa and normal stroma using laser capture microdissection. METHODS: Tissues were fixed from 11 patients undergoing colorectal resection for cancer, and laser capture microdissection was performed. Samples (4 per patient) were extracted for RNA, which was then used for focused gene arrays. In addition, protein expression of selected genes was determined by Western blot or immunohistochemistry. RESULTS: We showed differential expression patterns in cancer cells and surrounding stroma compared with their normal counterparts. Genes contributing to angiogenesis, cell cycle regulation, and proliferation were significantly increased in cancer cells compared with the adjacent normal mucosa. Genes contributing to angiogenesis, cancer invasion, and metastasis were significantly increased in surrounding cancer stromal cells compared with normal stroma. CONCLUSIONS: Delineating the differential patterns of gene expression between colon cancers and the surrounding reactive stroma will better determine the role of the stromal components in the progression of colon cancers and may lead to chemopreventive therapy targeted specifically to the stroma.
Adenocarcinoma↗
Polyphenol contents in grape-seed extracts correlate with antipica effects in cisplatin-treated rats.
BACKGROUND: Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting. MATERIALS AND METHODS: A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study. RESULTS: High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatin induced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001). CONCLUSIONS: The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.
Animals↗
Tannic acid stimulates glucose transport and inhibits adipocyte differentiation in 3T3-L1 cells.
Obesity is a major risk factor for Syndrome X and type II diabetes (T2D). However, most antidiabetic drugs that are hypoglycemic also promote weight gain, thus alleviating one symptom of T2D while aggravating a major risk factor that leads to T2D. Adipogenesis, the differentiation and proliferation of adipocytes, is a major mechanism leading to weight gain and obesity. It is highly desirable to develop pharmaceuticals and treatments for T2D that reduce blood glucose levels without inducing adipogenesis in patients. Previously, we reported that an extract from Lagerstroemia speciosa L. (banaba) possessed activities that both stimulated glucose transport and inhibited adipocyte differentiation in 3T3-L1 cells. Using glucose uptake assays and Western/Northern blot analyses as major tools and 3T3-L1 cells as a model, we showed that the banaba extract (BE) with tannin removed was devoid of the 2 activities, and tannic acid (TA), a major component of tannins, had the same 2 activities as BE. Inhibitors known to abolish insulin-induced glucose transport also blocked TA-induced glucose transport. We further detected that TA induced phosphorylation of the insulin receptor (IR) and Akt, as well as translocation of glucose transporter 4 (GLUT 4), the protein factors involved in the signaling pathway of insulin-mediated glucose transport. We also demonstrated that TA inhibited the expression of key genes for adipogenesis. Differences between samples with or without TA in all of the quantitative assays were significant (P < 0.05). These results suggest that TA may be useful for the prevention and treatment of T2D and its associated obesity. TA may have the potential to become the lead compound in the development of new types of antidiabetic pharmaceuticals that are able to reduce blood glucose levels without increasing adiposity.
3T3 Cells↗
Fluorescently tagged canine adenovirus via modification with protein IX-enhanced green fluorescent protein.
Canine adenovirus type 2 (CAV2) has become an attractive vector for gene therapy because of its non-pathogenicity and the lack of pre-existing neutralizing antibodies against this virus in the human population. Additionally, this vector has been proposed as a conditionally replicative adenovirus agent under the control of an osteocalcin promoter for evaluation in a syngeneic, immunocompetent canine model with spontaneous osteosarcoma. In this study, a CAV2 vector labelled with the fluorescent capsid fusion protein IX-enhanced green fluorescent protein (pIX-EGFP) was developed. Expression of the fluorescent fusion-protein label in infected cells with proper nuclear localization, and incorporation into virions, could be detected. The labelled virions could be visualized by fluorescence microscopy; this was applicable to the tracking of CAV2 infection, as well as localizing the distribution of the vector in tissues. Expression of pIX-EGFP could be exploited to detect the replication and spread of CAV2. These results indicate that pIX can serve as a platform for incorporation of heterologous proteins in the context of a canine adenovirus xenotype. It is believed that capsid-labelled CAV2 has utility for vector-development studies and for monitoring CAV2-based oncolytic adenovirus replication.
Adenoviruses, Canine↗
Haemopoietic mechanisms in murine allergic upper and lower airway inflammation.
Eosinophil recruitment to the airways, including involvement of haemopoietic eosinophil-basophil progenitors (Eo/B-CFU), is primarily regulated by interleukin-5 (IL-5) and eotaxin. In this study, we investigated the haemopoietic mechanisms in upper and lower airway eosinophilic inflammation. Ovalbumin (OVA) sensitized and challenged BALB/c mice were used to establish isolated upper (UAC), isolated lower (LAC), or combined upper and lower airway (ULAC) inflammation. Airway, blood and bone marrow responses were evaluated in each model. Numbers of airway eosinophils and CD4(+) cells were increased significantly in the nasal mucosa in UAC and ULAC mice, and in the lung tissue in LAC and ULAC groups. Levels of IL-5 and eotaxin were increased significantly in the nasal lavage fluid (NL) in UAC and ULAC mice, and in the bronchoalveolar lavage fluid (BAL) in LAC and ULAC groups. The proportion of IL-5-responsive bone marrow Eo/B-CFU was significantly higher than the control in all treatment groups, but peaked much earlier in the ULAC group. Kinetic studies revealed that IL-5 and eotaxin in NL, BAL and serum peaked between 2 and 12 hr after OVA challenge in ULAC mice, and at 24 hr in UAC mice, related to the timing of maximal progenitor responses. These data support the concept that the systemic mechanisms linking rhinitis to asthma depend on the location and extent of airway allergen exposure.
Animals↗
Effects of propyl gallate on interaction between TNF-alpha and sTNFR-I using an affinity biosensor.
AIM: To study the effects of propyl gallate on the interaction of tumor necrosis factor-alpha (TNF-alpha) with its soluble receptor, sTNFR-I. METHODS: Interactions between TNF-alpha and sTNFR-I were analyzed using an IAsys biosensor. sTNFR-I was immobilized on the carboxymethyl dextran (CMD) surface of the IAsys biosensor cuvettes, and TNF-alpha preincubated with different concentrations of propyl gallate was added to the cuvettes. The resonant angle shift caused by the binding between TNF-alpha and sTNFR-I was then recorded. RESULTS: sTNFR-I was immobilized on the CMD surface at a density of 2.76 ng/mm(2). TNF-alpha then bound the immobilized sTNFR-I specifically, and propyl gallate was able to enhance the binding between TNF-alpha and sTNFR-I in a dose-dependent manner. CONCLUSION: The binding between TNF-alpha and sTNFR-I is one of the targets that propyl gallate can act on in vivo. The IAsys biosensor offers a new clue as to the study on the mechanisms of action of propyl gallate.
Antioxidants↗
Non-invasive in situ simultaneous measurement of multi-parameter mechanical properties of red blood cell membrane.
The purpose of this study was to develop a new dynamic image analyzing technique that will give us the ability to measure the viscoelastic parameters of individual living red blood cells non-invasively, in situ and in real time. With this technique, the bending modulus KC, the shear elasticity mu and their ratio were measured under different temperatures, oxygen partial pressures and osmotic pressures. The results not only show the effects of external conditions on mechanical properties of cell membranes including deformability, flexibility, adhesive ability and plasticity, but also demonstrate that the technique can be used to measure cell membrane parameters continuously under several physiological and pathological conditions.
Adult↗
Abnormal glucose homeostasis and pancreatic islet function in mice with inactivation of the Fem1b gene.
Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively. Here, we have developed Fem1b knockout (Fem1b-KO) mice, with targeted inactivation of Fem1b, a homolog of the nematode fem-1 sex determination gene. We show that the Fem1b-KO mice display abnormal glucose tolerance and that this is due predominantly to defective glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion is also affected. The Fem1b gene is expressed in pancreatic islets, within both beta cells and non-beta cells, and is highly expressed in INS-1E cells, a pancreatic beta-cell line. In conclusion, these data implicate Fem1b in pancreatic islet function and insulin secretion, strengthening evidence that a genetic pathway homologous to nematode sex determination may be involved in glucose homeostasis and suggesting novel genes and processes as potential candidates in the pathogenesis of diabetes mellitus.
Animals↗