Highly sensitive and selective photoelectrochemical detection of bis(2-ethylhexyl)phthalate on broad-spectrum responsive and interfacial electronic interaction induced p-n BiOI/ZnO nanoarrays heterojunction.

Bis(2-ethylhexyl)phthalate (DEHP), an endocrine disruptor, shows carcinogenic, teratogenic, mutagenic and estrogenic effects. It is easy to release from plastic materials and migrate to soil environment, causing serious pollution and posing a great threat to human health. In our work, a photoelectrochemical (PEC) sensing platform for DEHP detection was constructed using BiOI/ZnO nanoarrays (NRs) as the transducer species and the DEHP aptamers as the biological recognition elements. ZnO NRs with three-dimensional and large diameter area were prepared by hydrothermal method to increase the light absorption capacity. Coupling BiOI in a narrow band gap with ZnO NRs strengthened visible-light absorption, while promoting charge carrier separation and transportation. This was attributed to the generation of an internal electric field between BiOI and ZnO NRs, exhibiting obvious photocurrent response. The as-developed PEC sensing platform demonstrated great sensing performance for detection of DEHP. Furthermore, the photocurrent varied and the logarithm of DEHP concentration showed a linear relationship from 1.0 × 10-11 to 5.0 × 10-7 mol/L, and the limit of detection was estimated to be 3.8 × 10-12 mol/L. In the meantime, while evaluating its usage in real soil samples, satisfying outcomes were realized. Thus, the as-proposed PEC sensing platform provided a potential device to monitor DEHP in the environment.

Gold nanocluster-confined covalent organic frameworks as bifunctional probes for electrochemiluminescence and colorimetric dual-response sensing of Pb2.

The development of bifunctional signal probes based on a single component is highly desirable for sensitive and simple dual-mode detection of Pb2+. Here, novel gold nanocluster-confined covalent organic frameworks (AuNCs@COFs) were fabricated as a bisignal generator to enable electrochemiluminescence (ECL) and colorimetric dual-response sensing. AuNCs with both intrinsic ECL and peroxidase-like activity were confined into the ultrasmall pores of the COFs via an in situ growth method. On the one hand, the space-confinement effect of the COFs closed the ligand motion-induced nonradiative transition channels of the AuNCs. As a result, the AuNCs@COFs exhibited a 3.3-fold enhancement in anodic ECL efficiency compared to the solid-state aggregated AuNCs using triethylamine as the coreactant. On the other hand, due to the outstanding spatial dispersibility of the AuNCs in the structurally ordered COFs, a high density of active catalytic sites and accelerated electron transfer were obtained, leading to the promotion of the enzyme-like catalytic capacity of the composite. To validate its practical applicability, a Pb2+-triggered dual-response sensing system was proposed based on the aptamer-regulated ECL and peroxidase-like activity of the AuNCs@COFs. Sensitive determinations down to 7.9 pM for the ECL mode and 0.56 nM for the colorimetric mode were obtained. This work provides an approach for designing single element-based bifunctional signal probes for dual-mode detection of Pb2+.

Research progress on photoelectrochemical sensors for contamination analysis in agricultural fields.

The establishment of rapid and efficient contamination detection methods in agricultural fields is of great significance for safeguarding agricultural production and human health, and for ensuring the healthy development of agricultural industries. As a booming analytical method, photoelectrochemical (PEC) sensors, which combine the advantages of electrochemical analysis and optical analysis, have received increasing research attention. Due to the complete separation of the excitation source (light) and the detection signal (current), the background signal of PEC sensors is greatly decreased, and their sensitivity is high. This review aims to cover the advances in PEC sensors for contamination analysis in agricultural fields over the past 5 years, including the analysis of heavy metals, antibiotics, pesticides, and toxins. The future prospects in this field are also discussed.

Prevalence trend and risk factors for anemia among patients with human immunodeficiency virus infection receiving antiretroviral therapy in rural China.

OBJECTIVE: To estimate the prevalence trend and risk factors for anemia in patients with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) in rural China. METHODS: We conducted cross-sectional studies among the same population in 2010, 2012, and 2014, based on data from standard medical record registers. Factors associated with anemia were evaluated using a logistic regression model. RESULTS: The number of patients with HIV infection included in each cross-sectional study was 1456 in 2010, 1531 in 2012, and 1567 in 2014, and the prevalence of anemia was 44.3%, 34.7%, and 27.6%, respectively. The prevalence of anemia was lower in female patients in 2010 [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.55-0.85]; however, there was no difference by sex in 2012 (OR 0.90; 95% CI 0.72-1.11) and 2014 (OR 1.05; 95% CI 0.84-1.32). Patients with a higher level of education had a lower risk of anemia in 2014 (OR 0.72; 95% CI 0.56-0.92), but there was no difference in 2010 (OR 1.00; 95% CI 0.79-1.25) and 2012 (OR 0.99; 95% CI 0.79-1.24). Patients who had received a longer duration of ART had a higher risk of anemia in 2014 (OR 1.74; 95% CI 1.15-2.64), but there was no difference in 2010 and 2012 (P > 0.05). Patients receiving Traditional Chinese Medicine (TCM) therapy had a lower risk of anemia. CONCLUSION: The prevalence of anemia among patients with HIV infection receiving ART decreased between 2010 and 2014 in Henan Province but was still higher than the prevalence in the general population of China. TCM therapy can potentially decrease the risk of anemia among patients with HIV infection.

Prevalence of liver injury among patients with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy in China.

OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome (AIDS) who received highly active antiretroviral therapy (HAART) in rural Henan Province in China, and to explore whether Traditional Chinese Medicine (TCM) treatment based on HAART would increase this risk. METHODS: This was a retrospective cross-sectional study. We collected medical information on patients with AIDS from two treatment databases in 2014. Criteria established by the AIDS Clinical Trials Group in 1996 were used for grading liver injury, classified based on the limit of normal (ULN) for alanine transaminase and aspartate aminotransferase: grade 1 (1.25-2.5 × ULN); grade 2 (2.6-5 × ULN); grade 3 (5.1-10 × ULN); and grade 4 (> 10 × ULN). Factors associated with liver injury were evaluated using a logistic regression model. RESULTS: A total 6953 patients with AIDS (3324 male and 3629 female patients) were enrolled into this study. The prevalence of liver injury was 22.0% (18.0% grade 1, 3.1% grade 2, 0.9% grade 3). In multivariate analysis, patients aged 34-45 years were more likely to have liver injury than patients in other age groups [adjusted odds ratio (AOR), 1.39; 95% CI, 1.01-1.91)]. Other factors associated with liver injury included male sex (AOR, 1.64; 95% CI, 1.46-1.85), HIV infection via blood (AOR, 1.47; 95% CI, 1.19-1.82), hepatitis B virus antibody positive (AOR, 1.07; 95% CI, 0.85-1.36), and hepatitis C virus (HCV) antibody positive (AOR, 2.76; 95% CI, 2.28-3.34). CONCLUSION: The prevalence of liver injury was relatively high among HAART-experienced patients. Several factors associated with liver injury included male sex, age 35-45 years old, HIV infection through blood, and concurrent HCV infection. TCM had no relationship with liver injury in patients receiving HAART.

Prevalence of anaemia among HIV patients in rural China during the HAART era.

The prevalence of anaemia among HIV patients receiving highly active antiretroviral therapy (HAART) in China has not been extensively studied. The purpose of this study was to estimate the prevalence of anaemia among HIV patients receiving HAART in China. This cross-sectional study was conducted based on data in routine record registers. Factors associated with anaemia were evaluated by logistic regression model. Among the 8632 HIV patients in this analysis, the overall prevalence of anaemia was 39.2%, and the prevalence of mild, moderate, and severe anaemia were 27.2%, 10.8%, and 1.2%, respectively. Anaemia was more prevalence among male, older, little time taken HAART and lower CD4 cell count. Patients taken TCM had lower prevalence of anaemia. The prevalence of anaemia among the HIV patients receiving HAART was high in this study. HIV patients with anaemia who are older and have CD4 cells count lower than 200 cells/mL require more attention. Traditional Chinese medicine may be a potential method to lower the frequency of anaemia.

[Clinical application characteristics of Danggui-Chuanxiong herb pair in Chinese medicines on basis of real-world].

To analyze the clinical application characteristics of Danggui-Chuanxiong(DG-CX) herb pair in Chinese medicines on basis of real-world, and provide reference for explaining the inherent compatibility regularity and the relationship between clinical applications and disease species. From April 1, 2014 to June 30, 2014, a total of 8 792 prescriptions with both "DG"and "CX" in a large third-grade class-A traditional Chinese medicine(TCM) hospital were selected to establish the database for analyzing the ratio, dosage, and corresponding disease species of DG-CX herb pair. The results showed that, "DG-CX" with ratio "1∶1" had the highest frequency in clinical application(42.4%); the dosage was mainly of 15 g for both DG and CX; the disease species were mainly of encephalopathy and pulmonary diseases. "DG-CX" herb pairs with a ratio greater than "1∶1" accounted for 33.3% of all the prescriptions, and the ratio "3∶2" appeared to be most frequent among them; the dosage was mainly of 15 g for DG and and 10 g for CX; the disease species were mainly of encephalopathy diseases. "DG-CX" herb pairs with a ratio less than "1∶1" accounted for 24.3% of all the prescriptions, and the ratio "2∶3" appeared to be most frequent among them; the dosage was mainly of 10 g for DG and 15 g for CX; the disease species were mainly of encephalopathy diseases. Statistical method was applied to study the compatibility and application characteristics of Chinese herb pairs in clinical prescriptions, effectively discover the medication regularity, provide theoretical basis for clinical herbal prescriptions and provide scientific guidance and reliable data for modern research of Chinese herb pairs.

ABCB1-overexpressing MG63/DOX cell xenograft model: maintain the MDR phenotype in vivo.

CONTEXT: Multi-drug resistance (MDR) constitutes a major obstacle in the effectiveness of chemotherapy. P-Glycoprotein (P-gp), the product of ABCB1 gene, is a transmembrane transporter that actively pumps cytotoxic drugs out of tumor cells resulting in MDR. OBJECTIVE: We sought to establish an MG63/DOX cell xenografts model that maintained the MDR phenotype and molecular properties in vivo in order to screen for new P-gp inhibitors. MATERIALS AND METHODS: The cytotoxicities of doxorubicin, paclitaxel and cytarabine were evaluated by MTT assays. P-gp activity was measured by rhodamine 123 accumulation using flow cytometry. P-gp expression in MG63/DOX cells and tumor tissues was detected by western blotting and immunohistochemistry. RESULTS: Our results showed that MG63/DOX cells exhibited 70-fold resistance to doxorubicin and more than 150-fold resistance to paclitaxel compared with parent MG63 cells. Furthermore, the ABCB1 inhibitor verapamil (10 µM) effectively reversed doxorubicin and paclitaxel resistance by 90- and 200-fold, respectively. The intracellular accumulation of rhodamine 123 was significantly increased (8.35-fold) in MG63/DOX cell, as compared to MG63 cells, in the presence of 10 µM verapamil. MG63/DOX tumor chunk xenografts had a high formation rate (88%). Finally, we found that the ABCB1 gene was overexpressed in different generations of solid tumors. DISCUSSION AND CONCLUSION: These data demonstrated that MG63/DOX tumor chunk subculture in vivo retained their molecular properties. This model could serve as a convenient system for the preclinical investigation of drug combinations and the screening of new agents to reverse ABCB1-mediated MDR.

Evaluation of impact of Herba Erigerontis injection, a Chinese herbal prescription, on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis. AIM OF THE STUDY: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis. RESULTS: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down. CONCLUSIONS: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.

Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice.

It has been confirmed that diabetes mellitus (DM) carries increased oxidative stress. This study evaluated the effects of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. After induction of diabetes, diabetic mice were administered daily doses of 50, 100 and 200 mg/kg salidroside for 28 days. Body weights, fasting blood glucose (FBG), serum insulin, TC (total cholesterol), TG (triglyceride), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. Results showed that salidroside possessed hypoglycemic activity and protective effects against diabetes-induced oxidative stress, which could significantly reduce FBG, TC, TG and MDA levels, and at same time increase serum insulin levels, SOD, GPx and CAT activities. Therefore, salidroside should be considered as a candidate for future studies on diabetes.

Inhibitory effects of limonin on six human cytochrome P450 enzymes and P-glycoprotein in vitro.

Among the various possible causes for drug interactions, pharmacokinetic factors such as inhibition of drug-metabolizing enzymes and transporters, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp), are regarded as the most frequent and clinically important. Limonin is a widely used dietary supplement and one of the most prevalent citrus limonoids, which are known to have inhibitory effects on CYPs and P-gp. In this study, the in vitro inhibitory effects of limonin on the major human CYP isoenzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) activities in human liver microsomes were examined using liquid chromatography-tandem mass spectrometry. The inhibitory effects of limonin on P-gp activity in a human metastatic malignant melanoma cell line WM-266-4 were examined using a calcein-AM fluorometry screening assay. It demonstrates that limonin has negligible inhibitory effects on human CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and P-gp. However, potent inhibition of CYP3A4 by limonin is observed with IC50 values of 6.20 µM (CYP3A4/testosterone) and 19.10 µM (CYP3A4/midazolam). This finding has important implications with regard to food-drug interactions between limonin and several narrow therapeutic index drugs that are metabolized by CYP3A4.

[In vitro inhibition of five traditional Chinese medicine injections on rat liver microsomal CYP3A].

OBJECTIVE: Qingkailing injection (QKLI), Jinnaduo injection (JNDI), Shuxuetong injection (SXTI), Shenmai injection (SMI) and Kangai injection (KAI) are widely used in China. To predict the herb-drug interactions in clinical application, they were evaluated for their in vitro inhibition effect on CYP3A in rat liver microsomes. METHOD: The rat liver microsomes were incubated with different doses of 5 kinds of traditional Chinese medicine injections (TCMIs) in the present of testosterone, a specific substrate of CYP3A. 6beta-hydroxytestosterone, the metabolite of testosterone, was monitored by HPLC to compare the inhibition effect of 5 TCMIs on CYP3A in rat liver microsomes. Ketoconazole was used as a positive control. RESULT: 10% QKLI reduced the formation of 6beta-hydroxytestosterone by approximately 93.0%, which is more significant than other four TCMIs. The half maximal inhibitory concentration (IC50) and the enzyme-inhibitor constant K(i) were 1.0% and 0.7% respectively. CONCLUSION: QKLI showed much stronger inhibition activity against CYP3A, comparing to other 4 TCMIs. The results revealed that QKLI may be involved in herb-drug interactions by inhibition of CYP3A.

In vitro inhibition of Huanglian [Rhizoma coptidis (L.)] and its six active alkaloids on six cytochrome P450 isoforms in human liver microsomes.

Huanglian (Rhizoma Coptidis) as a popular herb has been used for the treatment of various diseases such as diarrhea, eye inflammation and women's abdominal ailments. Alkaloids are considered to be responsible for its pharmacological effects. In this investigation, Huanglian and its six alkaloids (coptisine, epiberberine, berberine, jateorrhizine, palmatine and magnoflorine) were systematically evaluated for their inhibition of six cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes by the LC-MS/MS method. Huanglian showed the strongest inhibition of CYP2D6, followed by CYP1A2 and CYP3A4_T. The IC50 values were 5.8 µg/mL, 36.8 µg/mL and 59.2 µg/mL, respectively. Of the constituents tested, coptisine and epiberberine showed strong inhibition of CYP2D6 with IC50 values of 4.4 µM and 7.7 µM; berberine, jateorrhizine and palmatine showed weak inhibition of CYP2D6 with IC50 values of 45.5 µM, 49.4 µM and 92.6 µM, respectively; jateorrhizine showed moderate inhibition of CYP3A4_T with an IC50 value of 13.3 µM; coptisine showed weak inhibition of CYP1A2 with an IC50 value of 37.3 µM. In addition, activation was observed in coptisine/CYP2C9 and palmatine/CYP2C9/CYP2C19. Other CYP450 isoforms were not affected markedly by the six alkaloids. In conclusion, Huanglian showed in vitro inhibition of CYP2D6, the inhibition might be contributed mostly by protoberberine alkaloids, especially coptisine and epiberberine. Herb-drug interactions may occur through the CYP2D6 inhibition.

Effect of regular organic solvents on cytochrome P450-mediated metabolic activities in rat liver microsomes.

The effects of regular organic solvents on the metabolic activities of various human cytochromes P450 (P450s) have been reported. However, very little is known about their influence on metabolic activities mediated by P450s in the rat liver microsomes (RLM). The purpose of this study was to investigate the effects of organic solvents such as methanol, acetonitrile, dimethyl sulfoxide (DMSO), acetone, and ethanol on CYP1A, CYP2C, CYP2D, CYP2E, and CYP3A-mediated metabolism using RLM. The results showed that the activities of most rat P450 enzymes appeared to be organic solvent-dependent, and the metabolism of the tested probes were remarkably reduced when the concentration of organic solvents was up to 5% v/v, whereas most organic solvents demonstrated no significant interference when the concentration was below 1%, with the exception of DMSO. In addition, organic solvents exhibited different inhibitory effects, for example, CYP2D and CYP2E showed a significant reduction of activities at lower concentrations of organic solvents. Hence, this phenomenon should be taken into consideration when designing in vitro metabolism studies of new chemical entities. Therefore, we recommend acetonitrile as the most suitable solvent for RLM incubations, and the content of organic solvent should be kept lower than 1% v/v.