Elevated ApoB/ApoA-Ι ratio is associated with poor outcome in acute ischemic stroke.

BACKGROUND: Apolipoproteins are known atherogenic factors that play important roles in many mechanisms related to acute ischemic stroke (AIS). However, it is unclear whether the ApoB/ApoA-Ι ratio is related to the prognosis of patients with AIS. METHODS: We conducted a prospective cohort study in the Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University and investigated the association between ApoB/ApoA-Ι ratio and poor outcomes at 3 months of AIS. RESULTS: 1,247 patients that met the eligibility criteria were enrolled in our study. We found that ApoA-Ι (Adjusted odds ratios (adjOR) 0.529, 95 %CI 0.327-0.855), ApoB (adjOR 3.015, 95 %CI 1.746-5.207), and ApoB/ApoA-Ι ratio (adjOR 3.986, 95 %CI 2.220-7.155) were independently associated with poor outcomes in acute ischemic stroke. During subgroup analysis, the ApoB/ApoA-Ι ratio was more likely associated with poor AIS outcomes in males and patients younger than 80 with SAO(Small Artery Occlusion) and no history of diabetes or statin use. Restricted cubic spline analyses explored the correlation between poor outcomes and ApoB/ApoA-Ι ratio. CONCLUSIONS: Higher ApoB, lower ApoA-Ι, and higher ApoB/ApoA-Ι ratios were independently associated with poor outcomes in AIS. However, ApoB and ApoA-Ι were not related to hemorrhagic transformation in AIS.

Nomogram to predict 3-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. METHODS: We analyzed 258 patients with acute ischemic stroke who underwent MT from January 2018 to February 2021. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3-6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter's Z-test to assess the calibration performance of the risk prediction model. RESULTS: In our visual nomogram, gender (odds ratio [OR], 3.40; 95%CI, 1.54-7.54), collateral circulation (OR, 0.46; 95%CI, 0.28-0.76), postoperative mTICI (OR, 0.06; 95%CI, 0.01-0.50), stroke-associated pneumonia (OR, 5.76; 95%CI, 2.79-11.87), preoperative Na (OR, 0.82; 95%CI, 0.72-0.92) and creatinine (OR, 1.02; 95%CI, 1.01-1.03) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT. The area under the nomogram curve was 0.8791 with good calibration performance (P = 0.873 for the Spiegelhalter's Z-test). CONCLUSIONS: A novel nomogram consisting of gender, collateral circulation, postoperative mTICI, stroke-associated pneumonia, preoperative Na and creatinine can predict the 3-month unfavorable outcomes in stroke patients treated with MT.

Personalized antiplatelet therapy guided by clopidogrel pharmacogenomics in acute ischemic stroke and transient ischemic attack: A prospective, randomized controlled trial.

Background: Clopidogrel is frequently used in patients with ischemic stroke or transient ischemic attack (TIA), but its efficacy is hampered by inter-individual variability, due to genetic differences associated with clopidogrel metabolism. We conducted this randomized controlled trial to validate whether the personalized antiplatelet therapy based on clopidogrel pharmacogenomics and clinical characteristics leads to better clinical outcomes compared with standard treatment. Methods: Patients were randomly divided into the standard group or pharmacogenetic group, in which the pharmacogenetic group required the detection of the genotyping of CYP2C19*2, CYP2C19*3, and CYP2C19*17. Patients were followed up for 90 days for the primary efficacy endpoint of new stroke events, secondary efficacy endpoint of individual or composite outcomes of the new clinical vascular events, and the incidence of disability. The primary safety outcome was major bleeding. Results: A total of 650 patients underwent randomization, among which 325 were in the pharmacogenomics group while 325 were in the standard group. Our study found after a 90-day follow-up, the risk of stroke and composite vascular events in the pharmacogenomics group was lower than that in the standard group. The incidence of disability significantly decreased in the pharmacogenomics group. In addition, no statistically significant differences were observed in bleeding events between the two groups. Conclusion: The present study demonstrates that personalized antiplatelet therapy guided by clopidogrel pharmacogenomics and clinical characteristics can significantly improve the net clinical benefit of ischemic stroke or TIA patients during the 90-day treatment period without increasing bleeding risk.

Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin.

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel. Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models. Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07-0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06-0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08-0.72, P = 0.03 for 7-day Barthel Index, respectively]. Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone. Clinical Registration Number: 1800019911.

Left Atrial Enlargement is Associated with Stroke Severity with Cardioembolic and Cryptogenic Subtypes in a Chinese Population.

BACKGROUND: Left atrial enlargement is associated with increased risk for stroke. However, few studies that evaluated the correlation between left atrial size and ischemic stroke severity. In this study, we aim to evaluate the association between left atrial size and stroke severity, especially with cardioembolic and cryptogenic stroke in the Chinese population. METHODS: A total of 1271 patients with acute ischemic stroke were included in this study. Echocardiographic left atrial diameter was measured and indexed to height. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate-to-severe neurologic deficit was defined as NIHSS greater than or equal to 5. Patients were divided into mild, moderate, or severe abnormal left atrial size by tertile distribution. Binary logistic regression analysis was used to identify independent predictors of severe stroke after adjustment. RESULTS: Among all enrolled patients, 328 (25.8%) were classified into moderate-to severe stroke severity (NIHSS ≥ 5). In the multivariable model, compared with the lowest tertile of left atrial size, the odds ratio for moderate-to-severe neurologic deficit was 0.902 (95% CI, 0.644-1.264, P = .550) when left atrial size was the highest tertile. Of all patients, 190 patients were further categorized as cardioembolic and cryptogenic subtypes, and 70 (36.8%) were classified into moderate-to-severe stroke severity. After adjusting for confounders, compared with the lowest tertile, the top tertile of left atrial size was significantly associated with moderate-to-severe stroke (3.156, 95% CI, 1.143-8.711, P = .027). CONCLUSION: Left atrial enlargement was associated with more severe initial neurologic deficits of embolic subtypes (cardioembolic and cryptogenic stroke) in patients with acute ischemic stroke.

Intracranial Aneurysms After Intravenous Thrombolysis in Patient with Atrial Myxoma: A Case Study.

We administered intravenous thrombolytic therapy to a 51-year-old female patient with a 101-min stroke onset. The patient was unconscious during the manifestation of symptoms. Computed tomography angiography examination of the intracranial artery at the time of admission suggested that the left middle cerebral artery was occluded. The patient regained consciousness after the intravenous thrombolytic treatment was administered. On an urgent cerebral angiography, it was revealed that the recanalization of the left middle cerebral artery was successful. Although blood perfusion was restored, occlusion of the distal blood flow remained. The symptoms of the patient gradually improved after the treatment. However, 6 months after the onset of the condition, intracranial aneurysms formed distal to the recanalized arteries that were previously embolized. The full process underlying the development of cerebral embolism caused by atrial myxomas and subsequent formation of aneurysms is illustrated in this patient. Although the underlying mechanism remains unclear, intravenous thrombolysis can successfully restore cerebral blood flow in and may improve the prognosis of patients with cerebral embolism caused by cardiac myxoma. Despite the positive revascularization therapy, the occurrence of the complication of intracranial aneurysms is possible. Long-term follow-up to evaluate the progression of myxomatous aneurysms after cerebral embolism with conservative treatment may be a suitable strategy for managing such patients.

Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling.

BACKGROUND Glioblastoma, the most common and malignant glial tumor, often has poor prognosis. Tivantinib has shown its potential in treating c-Met-high carcinoma. No studies have explored whether tivantinib inhibits the development of glioblastoma. MATERIAL AND METHODS The correlation between c-Met expression and clinicopathological characteristics of glioblastoma was investigated. U251 and T98MG glioblastoma cells treated with tivantinib, PI3K inhibitor (LY294002), PI3K activator (740 Y-P), and/or mammalian target of rapamycin (mTOR) inhibitor were subjected to MTT assay or colony formation assay to evaluate cell proliferation. The expression of mTOR signaling and caspase-3 in tivantinib-treated glioblastoma cells was differentially measured by western blotting. RESULTS In a group of Chinese patients, expression of c-Met was elevated with the size of glioblastoma, but not with the other clinicopathological characteristics, including gender, age, grade, IDH status, 1p/19q status, and Ki67 status. High dose of tivantinib (1 µmol/L) obviously repressed the proliferation and colony formation of U251 and T98MG glioblastoma cells, but low dose (0.1 µmol/L) of tivantinib failed to retard cell proliferation. Tivantinib blocked PI3K/Akt/mTOR signaling but did not change the expression of cleaved caspase-3. PI3K activator 740 Y-P (20 µmol/L) significantly rescued tivantinib-induced decrease of cell proliferation. Tivantinib (1 µmol/L) in combination with PI3K inhibitor LY294002 (0.5 µmol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells. CONCLUSIONS c-MET inhibitor tivantinib blocks PIKE/Akt/mTOR signaling and hampers the proliferation of glioblastoma cells, which endows the drug a therapeutic effect.

Personalised antiplatelet therapy based on pharmacogenomics in acute ischaemic minor stroke and transient ischaemic attack: study protocol for a randomised controlled trial.

INTRODUCTION: Antiplatelet therapy combining aspirin and clopidogrel is considered to be a key intervention for acute ischaemic minor stroke (AIMS) and transient ischaemic attack (TIA). However, the interindividual variability in response to clopidogrel resulting from the polymorphisms in clopidogrel metabolism-related genes has greatly limited its efficacy. To date, there are no reports on individualised antiplatelet therapy for AIMS and TIA based on the genetic testing and clinical features. Therefore, we conduct this randomised controlled trial to validate the hypothesis that the individualised antiplatelet therapy selected on the basis of a combination of genetic information and clinical features would lead to better clinical outcomes compared with the standard care based only on clinical features in patients with AIMS or TIA. METHODS AND ANALYSIS: This trial will recruit 2382 patients with AIMS or TIA who meet eligibility criteria. Patients are randomly assigned in a 1:1 ratio to pharmacogenetic group and standard group. Both groups receive a loading dose of 300 mg aspirin and 300 mg clopidogrel on day 1, followed by 100 mg aspirin per day on days 2-365. The P2Y12 receptor antagonist is selected by the clinician according to the genetic information and clinical features for pharmacogenetic group and clinical features for the standard group on days 2-21. The primary efficacy endpoint is a new stroke event (ischaemic or haemorrhagic) that happens within 1 year. The secondary efficacy endpoint is analysed as the individual or composite outcomes of the new clinical vascular event (ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death). Baseline characteristics and outcomes after treatment will be evaluated. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Yangpu Hospital, Tongji University School of Medicine (No. LL-2018-KY-012). We will submit the results of this trial for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR1800019911; Pre-results.

Clinical characteristics and risk score for poor clinical outcome of acute ischemic stroke patients treated with intravenous thrombolysis therapy.

BACKGROUND: Tissue plasminogen activator (t-PA) is an effective therapy for acute ischemic stroke, but some patients still have poor clinical outcome. In this study, we investigated clinical characteristics of stroke patients and determined predictors for poor clinical outcome in response to t-PA treatment. METHODS: Clinical data from 247 patients were retrospectively reviewed. Clinical parameters that were associated with survival of patients were analyzed. Areas under receiver operating characteristic curves (ROC) were used to determine the feasibility of using various combinations of the clinical parameters to predict poor clinical response. The clinical outcome was defined according to the changes in Modified Rankin Scale. RESULTS: Overall, 145 patients had improved/complete recovery, 73 had no change, and 29 had worsening conditions or died during the in-clinic period. A univariate analysis showed that baseline characteristics including age, CRP, blood glucose level, systolic blood pressure, and admission NIHSS were significantly different (p < 0.05) among patients with different clinical outcome. A further multivariate analysis was then performed. Variables associated with poor clinical outcome (worsening/death) (p < 0.1) were included in the logistic regression model. Four parameters were retained in the model: Age, CRP, Blood glucose level, and Systolic blood pressure (ACBS). To allow a convenient usage of the ACBS classifier, the parameters were put into a scoring system, and the score at 7.7 was chosen as a cut-off. The ROC curve of this ACBS classifier has an area under the curve (AUC) of 0.7788, higher than other individual parameters. The ACBS classifier provided enhanced sensitivity of 69.2% and specificity of 74.3%. CONCLUSION: The ACBS classifier provided a satisfactory power in estimating the patients' clinical outcome. After further validating, the classifier may provide important information to clinicians for making clinical decisions.

Small RNA sequencing reveals dynamic microRNA expression of important nutrient metabolism during development of Camellia oleifera fruit.

To obtain insight into the function of miRNAs in the synthesis and storage of important nutrients during the development of Camellia oleifera fruit, Illumina sequencing of flower and fruit small-RNA was conducted. The results revealed that 797 miRNAs were significantly differentially expressed between flower and fruit samples of Camellia oleifera. Through integrated GO and KEGG function annotations, it was determined that the miRNA target genes were mainly involved in metabolic pathways, plant hormone signal transduction, fruit development, mitosis and regulation of biosynthetic processes. Carbohydrate accumulation genes were differentially regulated by miR156, miR390 and miR395 in the fruit growth and development process. MiR477 is the key miRNA functioning in regulation of genes and involved in fatty acid synthesis. Additionally, miR156 also has the function of regulating glycolysis and nutrient transformation genes.

Hierarchical Nanosheet-Built CoNi2S4 Nanotubes Coupled with Carbon-Encapsulated Carbon Nanotubes@Fe2O3 Composites toward High-Performance Aqueous Hybrid Supercapacitor Devices.

A hybrid supercapacitor system was designed with ternary Ni-Co sulfides (CoNi2S4) as cathode materials and Fe-based composites [carbon nanotubes (CNTs)@Fe2O3@C] as anode materials to achieve excellent overall electrochemical performance with high energy and power density as well as long lifespan. Here, hierarchical CoNi2S4 nanotubes were synthesized by a solvothermal route followed by sulfidation reaction for the first time, in which nanotubes were composed of interconnected ultrathin nanosheets. Consequently, such a unique nanosheet-built nanoarchitecture enables the CoNi2S4 cathode with multidimensional synergistic effect from one-dimensional nanotubes, two-dimensional nanosheets, and three-dimensional frameworks. Profiting from its structural merits, the as-prepared CoNi2S4 nanotubes deliver a high capacitance of 2552 F g-1 at 1 A g-1 with a high rate capacity of 81% at 25 A g-1. In addition, the CNTs@Fe2O3@C anode materials-incorporating carbon-encapsulated ultrafine Fe2O3 nanoparticles into CNT matrices-were achieved by atomic layer deposition and acetylene thermal decomposition, which realize excellent electrochemical properties (678 F g-1 at 1 A g-1 and capacity retention of 82% at 25 A g-1) that matched well with CoNi2S4 cathode materials. With the well-designed nanostructure and matching of materials and properties, the corresponding aqueous hybrid device exhibits a wide output voltage window of 0-1.75 V with a maximum energy density of 90.5 W h kg-1 at a power density of 1.84 kW kg-1. Meanwhile, a high energy density of 73.1 W h kg-1 can be retained at an ultrahigh power density of 26.9 kW kg-1. Moreover, the hybrid device has a stable cycling ability with 82.1% retention over 5000 cycles. This coordinative design strategy integrating the cathode and anode electrodes developed in this work provides a novel way to manufacture next-generation energy-storage device with high performance and safety.

Intrinsically fluorescent and highly functionalized polymer nanoparticles as probes for the detection of zinc and pyrophosphate ions in rabbit serum samples.

Intrinsically fluorescent polymer nanoparticles (F-PNPs) were synthetized from 2-hydroxy-5-methylisophthalaldehyde and melamine by solvothermal method. F-PNPs can emit strong yellow green fluorescence at 542 nm without the conjugation to any external fluorescent agent and surface modification. Owing to the abundant amino and hydroxyl groups on their surface, the F-PNPs possess multiple binding sites, good biocompatibility and excellent water-solubility. Addition of Zn2+ to the F-PNPs solution resulted in a blue shift (Δλ=40 nm) with obvious enhancement in the fluorescence intensity at 502 nm; while there was negligible change in the presence of other metal ions. The subsequent treatment with pyrophosphate (PPi) can cause fluorescence recovery of F-PNPs by pulling the Zn2+ out of the coordination cavity of F-PNPs-Zn2+ nanocomposites. No interference was observed from other anions and nucleotides, making the F-PNPs-Zn2+ ensembles highly sensitive and selective nanoprobes for PPi. The detection limit is 2.75 × 10-8 M/L and 7.63 × 10-8 M/L for Zn2+ and PPi, respectively. The proposed nanoprobes were then used for detecting the recovery of Zn2+ and PPi in rabbit serum samples, which were found to be 99.4-104.2% and 98.6-104.7%, respectively. The present strategy for the fabrication of nanoparticles may offer a new sight for the preparation of polymer nanostructures. The F-FNPs based probes can provide an accurate method for the detection of Zn2+ and PPi in serum samples.

Regio- and Stereoselective Hydrosulfonation of Alkynylcarbonyl Compounds with Sulfinic Acid in Water.

We report the atom-economic and environmentally friendly synthesis of Z-ß-sulfonyl-a,ß-unsaturated carbonyl compounds in water. The mechanism study reveals that the hydrosulfonylation of alkynylcarbonyl compounds with sulfinic acids proceeds via a mechanism that features a sulfinic acid molecule protonating an alkynyl motif to form the ethenium intermediate, which subsequently reacted with a sulfonyl anion to afford the desired products. The ethenium intermediate differentiated electronic and steric demands between the two substituents on the C≡C triple bond of the alkyne substrates to exhibit high regio- and stereoselectivity from a wide range of Z-ß-sulfonyl-a,ß-unsaturated carbonyl compounds.

A sensitive strategy for label-free and time-resolved fluorescence assay of thrombin using Tb-complex and unmodified gold nanoparticles.

Gold nanoparticles (GNPs) can effectively differentiate the unfolded and folded aptamer, and quench the fluorescence of terbium ternary complexes (Tb-complexes), thus the authors herein report a sensitive strategy for protein detection, using label-free aptamer, Tb-complexes and GNPs. In the presence of thrombin, the aptamer is inclined to form G-quartet, and the folded aptamer cannot adsorb on the surface of GNPs, inducing the GNPs aggregation in the presence of 0.5 mol L(-1) salt. After centrifugation at low speed to remove the aggregated GNPs, the quenching capability of the supernatant for Tb-complexes is decreased. The fluorescence intensity of Tb-complexes increases as the concentration of thrombin increases. Due to the highly specific recognition ability of the aptamer for thrombin and the strong quenching property of GNPs for Tb-complexes, the proposed protocol has good selectivity and high sensitivity for thrombin. Under the optimum conditions, a linear range from 1.0 × 10(-9) M to 1.0 × 10(-8) M is obtained with a detection limit of 0.14 nM, which is much lower than those commonly obtained for colorimetric sensors and some fluorescent sensors. The signal of Tb-complexes can be measured by time-resolved manner which made most of the unspecific fluorescent background signals be eliminated. The proposed sensor has been successfully applied in complicated biological samples for thrombin detection, and it can provide a promising potential for label-free aptamer-based protein detection.

catena-Poly[[[(5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane-κ(4)N)nickel(II)]-µ-oxido-[dioxidotungstate(VI)]-µ-oxido] tetra-hydrate].

In the title compound, {[NiWO(4)(C(16)H(36)N(4))]·4H(2)O}(n), the Ni(II) ion lies on an inversion center and is octahedrally coordinated by four N atoms of the tetradentate macrocyclic 5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane (L) ligand in the equatorial plane and two O atoms of [WO(4)](2-) anions in axial positions. Each [WO(4)](2-) anion bridges two adjacent [NiL](2+) cations, forming a chain along [001]. The chains are further connected via N-H⋯O, O-H⋯O and C-H⋯O hydrogen-bonding inter-actions, generating a three-dimensional structure.

Determination of ammonia-oxidizing bacteria based on time-resolved fluorescence and tandem probe.

To study the ecology of ammonia-oxidizing bacteria (AOB), quantitative techniques are essential. In this report, the authors introduced an innovative method based on time-resolved fluorescence to quantify AOB as a representative of the major functional microorganisms in sewage water treatment. A bifunctional europium complex with the characteristics of long lifetime and intense luminescence was used as labels in the experiments. In the detection, the capture probe and dye-labeled reporter probe could form a two-probe tandem with the target sequence, and the determination of target DNA was done by monitoring the time-resolved fluorescence signals of europium complex-labeled reporter probe left on the glass slide surface. The experiment conditions consisting of concentration of capture probe, hybridization temperature, hybridization time and washing time were optimized. This method presents satisfactory specificity to common bacteria such as Nitrobacter winogradskyi, Escherichia coli and Paenibacillus polymyxa. The detection limit was 3.65 × 10(-11)mol L(-1). This detection system enables us to rapidly and sensitively analyze the microbial population variety in sewage water treatment.

Synthesis of substituted-phenyl-1,2,4-triazol-3-thione analogues with modified D-glucopyranosyl residues and their antiproliferative activities.

A series of D-glucopyranosyl-1,2,4-triazole-3-thione derivatives 1a-1d were synthesized by the reaction of 1,2,4-triazole-3-thione Schiff bases 5a-5d with 2,3,4,6-tetra-O-acetyl-sigma-D-glucopyranosyl bromide. We demonstrate the conversion of 2 to 5, without the necessity of purification of both oxadiazole and triazole intermediates to afford the compounds 5. Their structures were confirmed by standard studies of (1)H NMR, IR, MS and elemental analysis. Analogues 5 and 1 have shown cytotoxic activity against human MCF-7 and Bel-7402 malignant cell lines.

Bacteria-modified amperometric immunosensor for a Brucella melitensis antibody assay.

A novel amperometric immunosensor setup is described which uses horseradish peroxidase (HRP) as a label in conjunction with a current-based Brucella sensor. The Bacteria modified immunosensor was constructed by using a biocomposite formed by dispersing graphite powder into a mixture of Brucella melitensis and silicate polymer gel. The enzyme-labeled antibody can readily diffuse toward the encapsulated antigen (Brucella melitensis), which retains its binding properties, and the association reaction is easily detected at the surface exposed to the solution. The use of an oaminophenol (o-AP) substrate and amperometric detection at -150 mV (vs. SCE) results in a relatively low detection limit of 3.5 ng/ml and a linear detection range of 3.5 ng/ml to 200 ng/ml. Based on an optimized parameter, the prepared sensor was used to detect the Brucella melitensis antibody in serum samples by using a competitive binding assay. The results demonstrate the feasibility of employing the proposed immunosensor for the detection for Brucella melitensis antibody in a clinical analysis.

Glycosylated metalloporphyrins as neutral carriers for PVC membrane electrodes.

In this paper, the synthesis of a novel ionophore, chloro[5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-beta-D-glucopyranosyl)-1-O-phenyl]porphinato]manganese (MnT(o-glu)PPCl), and its application as a neutral carrier for a PVC membrane electrode are described. The MnT(o-glu)PPCl-based PVC membrane electrode shows a potentiometric responses to SCN- over a concentration range of 3.4 x 10(-7) - 1.0 x 10(-1) mol L(-1) with a Nernstian slope and a response time of 20 s. The electrode exhibits an anti-Hofmeister selectivity toward SCN- with respect to common coexisting anions. As active materials, MnT(o-glu)PPCl shows better selectivity toward SCN- than chloro(tetraphenylporphinato)manganese (MnTPPCl). The effect of the electrode membrane compositions has been studied and the experimental conditions were optimized. The electrode was applied to the determination of SCN- in body fluids with satisfactory results.