Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor.

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

Study on the detection of anthrax by ICP-MS based on gold nanoparticle labeling.

BACKGROUND: In recent years, inductively coupled plasma mass spectrometry (ICP-MS) has been widely used in the field of molecular biology because of its unique advantages. Anthrax is a widespread and long-standing infectious disease, which affects and restricts people's work and life seriously. OBJECTIVE: The study goal is to develop a new method for the detection of anthrax. METHODS: A rapid, sensitive and accurate method for the detection of anthrax characteristic DNA was proposed by combing gold nanoparticles (AuNPs) and inductively coupled plasma mass spectrometry. RESULTS: The linear range of this method is 100-2500 pmol/L and the limit of detection of 16.61 pmol/L. CONCLUSION: The proposed method has numerous advantages, including simplicity of operation, high sensitivity, and specificity, which provides a new idea for the detection of anthrax. Importantly, this methodology has good potential for the detection of other biological substances such as bacteria and viruses by changing the modification sequence on the nanoparticle probe.

Preliminary study on the effect of ozone exposure on blood glucose level in rats.

BACKGROUND: In recent years, people have paid more and more attention to the health hazards caused by O3 exposure, which will become a major problem after fine particulate matter (PM). OBJECTIVE: To investigate the effects of ozone (O3) exposure on blood glucose levels in rats under different concentrations and times. METHODS: Eighty rats were divided into control group and three ozone concentration groups. Each group was continuously exposed for 1d, 3d and, 6d, and exposed for 6 hours daily. After exposure, GTT, FBG, and random blood glucose were measured. RESULTS: The FBG value increased significantly on the 6th day of 0.5 ppm and the 3rd and 6th days of 1.0 ppm exposure compared with the control group (P< 0.05). The random blood glucose value was significantly increased on the 3rd and 6th days of each exposure concentration (P< 0.05). When exposed to 1 ppm concentration, the 120 min GTT value of 1 d, 3 d and, 6 d was significantly higher than that of the control group (P< 0.05). CONCLUSION: After acute O3 exposure, the blood glucose level of rats was affected by the exposure concentration and time. The concentration of 0.1 ppm had no significant impact on FBG and random blood glucose, and O3 with a concentration of 0.1 ppm and 0.5 ppm had no significant impact on values of GTT at 90 min, and 120 min.

Potential of UK and US newspapers for shaping patients' knowledge and perceptions about antidiabetic medicines: a content analysis.

BACKGROUND: Information about how newspapers portray antidiabetic medicines to readers is lacking. This study investigated the reporting on antidiabetic medicines in the most widely circulated newspapers published in the United Kingdom (UK) and the United States (US) over a 10-year period. METHODS: The Nexis UK database was used to identify and select relevant articles. Systematic content analysis of the articles which met the inclusion criteria (articles of any format that contained reference to antidiabetic medicines) within the highest circulated newspapers in the UK and US between 2009 and 2018 was conducted. Inter-rater reliability of coding was established using a 10% sample of the identified articles. RESULTS: A total of 560 (369 UK and 191 US) relevant newspaper articles were retrieved. In the UK, the number of relevant articles showed a slightly increasing trend over the study period, while in the US, article numbers declined over the study period. Safety/risk of antidiabetic medicines was the most frequent theme covered by the articles (34.6%). Over one-third of the newspaper articles were written from a clinical perspective (37.7%). Insulin was the most commonly discussed class of antidiabetic medicine (23.1%). Control of blood sugar levels (53.1%) and side effects/toxicity (92.7%) were the most frequently reported benefit and risk of antidiabetic medicines, respectively. The most frequently reported organ systems harmed by antidiabetic medicines were the cardiovascular, endocrine and gastrointestinal systems. The UK newspapers were more likely to report the benefits of antidiabetic medicines (p = 0.005), while the US articles were more likely to report on harms/risks (p = 0.001). The majority of relevant articles (91.8%) were judged as having a balanced judgement, while 8.2% of the articles were rated as exaggerated. CONCLUSIONS: This study has revealed that antidiabetic medicines are indeed reported on by UK and US newspapers. As media portrayal has the potential to negatively or positively influence patients' views of their medication for diabetes, healthcare professionals should check on patients' beliefs and knowledge about their medication and proactively provide objective and balanced information (including promotion of medication adherence).

Adherence to metformin in adults with type 2 diabetes: a combined method approach.

BACKGROUND: Medication adherence, one of the most important aspects in the process of optimal medicines use, is unfortunately still a major challenge in modern healthcare, and further research is required into how adherence can be assessed and optimised. The aim of this study was to use a combined method approach of self-report and dried blood spot (DBS) sampling coupled with population pharmacokinetic (PopPK) modelling, to assess adherence to metformin in adult patients with type 2 diabetes. Further aims were to assess metformin exposure levels in patients, determine factors associated with non-adherence with prescribed metformin, and to explore the relationship between adherence and therapeutic outcomes. METHODS: A combined method approach was used to evaluate metformin adherence in patients with type 2 diabetes who had been prescribed metformin for a minimum period of 6 months. Patients were recruited from consultant-led diabetic outpatient clinics at three hospitals in Northern Ireland, UK. Data collection involved self-reported questionnaires [Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire and Centre for Epidemiologic Studies Depression Scale], direct measurement of metformin concentration in DBS samples, and researcher-led patient interviews. The DBS sampling approach was coupled with population pharmacokinetic (PopPK) modelling, which took account of patient characteristics, metformin dosage and type of formulation prescribed (immediate or sustained release). RESULTS: The proportion of patients considered to be adherent to their prescribed metformin, derived from self-reported MARS scores and metformin concentration in DBS samples, was 61.2% (74 out of 121 patients). The majority (n = 103, 85.1%) of recruited patients had metformin exposure levels that fell within the therapeutic range. However, 17 patients (14.1%) had low exposure to metformin and one patient (0.8%) had undetectable metformin level in their blood sample (non-exposure). Metformin self-administration and use of a purchased adherence pill box significantly increased the probability of a patient being classified as adherent based on logistic regression analysis. Both HbA1c and random glucose levels (representing poor glycaemic control) in the present research were, however, not statistically linked to non-adherence to metformin (P > 0.05). CONCLUSIONS: A significant proportion of participating patients were not fully adherent with their therapy. DBS sampling together with the use of a published PopPK model was a useful, novel, direct, objective approach to estimate levels of adherence in adult patients with type 2 diabetes (61.2%).

Impact of dietary aflatoxin on immune development in Gambian infants: a cohort study.

BACKGROUND: Chronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective was to investigate the impact of AF exposure on immune development in early infancy using thymic size and antibody (Ab) response to vaccination as indicators of immune function. METHODS: A total of 374 infants born between May 2011 and December 2012 were enrolled into the current study. These infants were recruited from a larger, randomised trial examining the impact of nutritional supplementation of mothers and infants on infant immune development (the Early Nutrition and Immune Development Trial). Thymic size (Thymic Index, TI) was measured by sonography at 1 week, 8 weeks, 24 weeks and 52 weeks of infant age. Infants were given the diphtheria-tetanus-pertussis (DTP) vaccine at 8 weeks, 12 weeks and 16 weeks of age, and Ab responses to each vaccine measured at 12 weeks and 24 weeks of age. AF-albumin (AF-alb) adduct levels in infant blood were measured by ELISA as the biomarker of AF exposure. RESULTS: The geometric mean (GM) level of AF-alb increased with age. Only half of infants had detectable AF-alb with a GM of 3.52 pg/mg at 24 weeks, increasing to 25.39 pg/mg at 52 weeks, when 98% of infants had AF-alb >limit of detection. Significant negative association of AF-alb level with TI was seen in infants during the first 24 weeks, especially at 8 weeks of age (p<0.001), which is the time point of fastest thymus growth. There were no associations between AF exposure level and Ab response to pertussis and tetanus, but a significant positive correlation was observed between AF-alb level and Ab titre to diphtheria (p<0.005). CONCLUSIONS: High levels of AF exposure during early infancy may impact on infant immune development. TRIAL REGISTRATION NUMBER: ISRCTN49285450.

A Fluorogenic and Chromogenic Probe Distinguishes Fluoride Anions and Thiols: Implications for Discrimination of Fluoride-Containing G Series and Sulfur-Containing V Series Nerve Agents.

A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, ß-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the µM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.

Development and characterisation of novel poly (vinyl alcohol)/poly (vinyl pyrrolidone)-based hydrogel-forming microneedle arrays for enhanced and sustained transdermal delivery of methotrexate.

Methotrexate (MTX) is one of the mainstays of treatment for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) and it is mainly administered either orally or by subcutaneous (SC) injection, which are not so satisfactory. While orally administered MTX is associated with variable bioavailability and causes gastrointestinal side effects, including nausea and vomiting, SC injection is painful and produces high peak blood levels of MTX. Transdermal delivery presents an attractive alternative administration route. However, MTX passive permeation through the skin is hindered by the skin barrier and MTX physicochemical properties. To address these issues, hydrogel-forming microneedle arrays (HFMN) and a patch-like reservoir loaded with MTX (MTX-RV) were developed and combined to form a minimally invasive patch to deliver MTX transdermally in a sustained manner. HFMN were prepared from an aqueous blend of poly (vinyl alcohol) (PVA) and poly (vinyl pyrrolidone) (PVP) which was crosslinked chemically with citric acid (CA) at 130˚C. MTX-RV was prepared from hydroxypropyl methylcellulose (HPMC) and glycerol. Both the HFMN and MTX-RV were fully characterised and then combined to form an integrated patch, which was evaluated ex vivo and in preclinical studies. The HFMN demonstrated a satisfactory mechanical strength and insertion capability into excised neonatal porcine skin, as well as moderate swelling properties. The MTX-RV incorporated a high dose of MTX (150.3 ± 5.3 µg/mg) without precipitation. The integrated patch delivered MTX at a steady-state flux of 506.8 ± 136.9 µg.cm2/h in an ex vivo setup. Furthermore, in preclinical studies performed in Sprague Dawley rats, MTX appeared in blood after 1 h from patch application at a concentration of 7.6 ± 2.0 nM. MTX blood level increased gradually to reach its peak, Cmax = 35.1 ± 5.1 nM, at 24 h. Importantly, the HFMN were removed intact from the skin with only mild erythema, despite the cytotoxic nature of MTX. Accordingly, the integrated patch produced in this work represents a promising minimally invasive transdermal drug delivery system that can overcome the skin barrier and deliver MTX in a sustained manner. This may help in minimising or even avoiding the nausea and vomiting, associated with the conventional administration routes.

Fe3O4 hard templating to assemble highly wrinkled graphene sheets into hierarchical porous film for compact capacitive energy storage.

Highly wrinkled graphene film (HWGF) with high packing density was synthesized by combining an electrostatically self-assembling process, a vacuum filtration-induced film assembling process and capillary compression. Fe3O4 nanoparticles were used as a low-cost and environment-friendly hard template. Hierarchical porosity and high packing density were achieved with the aid of capillary compression in the presence of Fe3O4 nanoparticles. This strategy enables integration of highly wrinkled graphene sheets to form highly compact carbon electrodes with a continuous ion transport network. The generated HWGF exhibited a high packing density of 1.53 g cm-3, a high specific surface area of 383 m2 g-1 and a hierarchically porous structure. The HWGF delivered a high capacitance of 242 F g-1 and 370 F cm-3 at 0.2 A g-1 in 6 M KOH aqueous electrolyte system with excellent rate capability (202 F g-1 and 309 F cm-3 retained at 20 A g-1). The capacity retention rate reached 97% after 10 000 cycles at 1 A g-1. The HWGF-based supercapacitor exhibited a high energy density of 17 W h kg-1 at the power density of 49 W kg-1. Such high capacitive performances could be attributed to the highly dense but porous graphene assemblies composed of highly wrinkled graphene sheets.

Impaired growth in rural Gambian infants exposed to aflatoxin: a prospective cohort study.

BACKGROUND: Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins. METHODS: A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling. RESULTS: Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (ß = - 0·04, P = 0·015; ß = - 0·05, P = 0.003; ß = - 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (ß = - 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (ß = - 0·01, P = 0·003; ß = - 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = - 0·12; P = 0·043). CONCLUSIONS: This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.

Comparison of urinary aflatoxin M1 and aflatoxin albumin adducts as biomarkers for assessing aflatoxin exposure in Tanzanian children.

PURPOSE: To determine levels of urinary aflatoxin M1 (AFM1) in children and correlate the concentrations with previously reported aflatoxin albumin adduct (AF-alb) levels in these children. MATERIALS AND METHODS: Matched urine and blood samples were collected from 84 Tanzanian children aged 6-14 months old. From 31 children in one village (Kigwa), samples were collected at three time points six months apart. Samples were collected from 31 and 22 children from two different regions at the second time point only. Urinary AFM1 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit with a modified protocol to improve sensitivity. AF-alb was measured using an established ELISA method. RESULTS: The relative ranking of the three villages for exposure to aflatoxin based on either AFM1 or AF-alb biomarker measurements was the same. In Kigwa village, both AFM1 and AF-alb levels were higher at six months post-harvest compared to baseline. However, at the next visit, the AFM1 levels dropped from a GM (interquartile range) of 71.0 (44.7, 112.6) at visit two to 49.3 (31.5, 77.3) pg/ml urine, whereas AF-alb levels increased from 47.3 (29.7, 75.2) to 52.7 (35.4, 78.3) pg/mg albumin between these two visits, reflecting the fact that AFM1 measures short-term exposure, whereas AF-alb measures longer term exposure. There was a correlation between AFB1 intake and AFM1 excretion (r= 0.442, p ≤ 0.001). CONCLUSIONS: Urinary AFM1 is a good biomarker for AFB1 exposure in Tanzanian children, reflecting geographical and temporal variations in exposure to this foodborne toxin.

Quantification of amlodipine in dried blood spot samples by high performance liquid chromatography tandem mass spectrometry.

A sensitive and specific method, utilising high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was developed for the quantitative determination of amlodipine in dried blood spot (DBS) samples. Chromatographic separation was achieved using a Waters XBridge C18 column with gradient elution of a mixture of water and acetonitrile containing 0.1% formic acid (v/v). Amlodipine was quantified using a Waters Quattro Premier mass spectrometer coupled with an electro-spray ionization (ESI) source in positive ion mode. The MRM transitions of 408.9 m/z→238.1m/z and 408.9→294.0 m/z were used to quantify and qualify amlodipine, respectively. The method was validated across the concentration range of 0.5-30ng/mL by assessing specificity, sensitivity, linearity, precision, accuracy, recovery and matrix effect according to the Food and Drug Administration (FDA) guidelines. This method was also validated clinically within a large pharmacoepidemiological study in which amlodipine blood concentration was determined in patients who had been prescribed this medication.

Facile fabrication of hierarchical film composed of Co(OH)2@Carbon nanotube core/sheath nanocables and its capacitive performance.

A hierarchical film composed of Co(OH)2@carbon nanotube (CNT) core/sheath nanocables (CCNF) was generated via a simple and rapid electrophoretic deposition method. It is found that the Co(OH)2 sheath was uniformly anchored on the surface of conductive CNT core. The Co(OH)2 sheath, with a thickness of ∼20 nm, was composed of numerous very tiny nanoparticles. Such a unique nanostructure endows the CCNF with a high surface area of 126 m2 g-1 and a hierarchical porosity, resulting in a large accessible surface area for redox activity. As expected, the CCNF exhibits high specific capacitance and excellent rate performance. Its specific capacitance reached 1215 F g-1 under a low current density of 1 A g-1 and was maintained at 832 F g-1 when the current density was increased 20 times to 20 A g-1. A high capacitance retention of 99.3% was achieved after 10 000 cycles at 1 A g-1. Such intriguing capacitive behavior is attributed to the synergistic effect of the CNT core and the Co(OH)2 sheath.

Dietary exposure to aflatoxin and micronutrient status among young children from Guinea.

SCOPE: Aflatoxin exposure coincides with micronutrient deficiencies in developing countries. Animal feeding studies have postulated that aflatoxin exposure may be exacerbating micronutrient deficiencies. Evidence available in human subjects is limited and inconsistent. The aim of the study was to investigate the relationship between aflatoxin exposure and micronutrient status among young Guinean children. METHODS AND RESULTS: A total of 305 children (28.8 ± 8.4 months) were recruited at groundnut harvest (rainy season), of which 288 were followed up 6 months later postharvest (dry season). Blood samples were collected at each visit. Aflatoxin-albumin adduct levels were measured by ELISA. Vitamin A, vitamin E and ß-carotene concentrations were measured using HPLC methods. Zinc was measured by atomic absorption spectroscopy. Aflatoxin exposure and micronutrient deficiencies were prevalent in this population and were influenced by season, with levels increasing between harvest and postharvest. At harvest, children in the highest aflatoxin exposure group, compared to the lowest, were 1.98 (95%CI: 1.00, 3.92) and 3.56 (95%CI: 1.13, 11.15) times more likely to be zinc and vitamin A deficient. CONCLUSION: Although children with high aflatoxin exposure levels were more likely to be zinc and vitamin A deficient, further research is necessary to determine a cause and effect relationship.

Structure-tunable Janus fibers fabricated using spinnerets with varying port angles.

The preparation of Janus fibers using a new side-by-side electrospinning process is reported. By manipulating the angle between the two ports of the spinneret emitting the working fluids, Janus nanofibers with tunable structures in terms of width, interfacial area and also volume of each side can be easily fabricated.

MicroRNAs: potential biomarkers for disease diagnosis.

MicroRNAs (miRNAs) are a group of endogenous noncoding small RNAs characterized by high conservation; furthermore, various studies have shown the capability of miRNAs to impact diseases. For example, a study shows that cell-free miRNAs are stable in bodily fluids, which gives circulating miRNAs the ability to be potential biomarkers for noninvasive diagnosis. Additionally, accumulating studies have supported that miRNAs can function as suppressor genes, again demonstrating their effect on disease. This review introduces this particular role of miRNAs as well as analyzes the prospect of miRNAs as biomarkers and the capacity for using miRNA-based resources to benefit mankind.

Sensitized terbium(III) macrocyclic-phthalimide complexes as luminescent pH switches.

Four new macrocyclic-phthalimide ligands were synthesised via the coupling of N-(3-bromopropyl)phthalimide either to cyclen (1,4,7,10-tetraazacyclododecane) itself or its carboxylate-functionalized analogues, and photophysical studies were carried out on their corresponding Tb(III) complexes in aqueous media as a function of pH. Luminescence intensities of Tb·L1a­Tb·L3a were in 'switched off' mode under acidic conditions (pH < 4), and were activated on progression to basic conditions as the phthalimido functions therein were hydrolysed to their corresponding phthalamates Tb·L1b­Tb·L3b. Emission of phthalamate-based macrocyclic Tb(III) complexes Tb·L1b­Tb·L3b was in 'switched on' mode between pH 4 and 11, exhibiting high quantum yields (Φ) and long lifetimes (τ) of the order of milliseconds at pH ~ 6. Tb(III) emissions were found to decline with increasing number of chromophores. The values of Φ and τ were 46% and 2.4 ms respectively for Tb·L1b at pH ~ 6 when activated. This is the best pH-dependent sensor based on a Tb(III) complex reported to date, benefiting from the macrocyclic architecture of the ligand.

A chemically unlocked binary molecular switch.

A highly luminescent and sensitive terbium complex of a ligand comprising of a phthalimide group appended to a DO3A moiety is an active pH sensor that is conditional on its previous pH.

Fluorogenic and chromogenic probe for rapid detection of a nerve agent simulant DCP.

A fluorogenic and visual probe was devised to detect diethyl chlorophosphate (DCP), a nerve agent simulant. The probe, N-(rhodamine B)-lactam-2-aminoethanol (RB-AE), undergoes oxazoline formation following phosphorylation in the presence of DCP, which gives rapid and clear fluorescence and color change in the assay solutions.

[Cloning, expression and evaluation of Saccharomyces cerevisiae ADH2].

In order to clone and express alcohol dehydrogenase II (ADH2) gene from Saccharomyces cerevisiae in E. coli BL21 (DE3) efficiently, we extracted the total RNA as template and obtained ADH2 gene by RT-PCR and connected ADH2 gene to pTAT plasmids to gain recombinant expression plasmid pTAT-ADH2, then transformed this recombinant expression plasmid pTAT-ADH2 into E. coli BL21 (DE3). The recombinant was induced by IPTG to express ADH2. After purification, ADH2 activity was tested in vitro and toxicologic test was done in mouse. Sequence test showed that the acquired fragments exhibited 90% homology to ADH2 gene sequence from GenBank report. The target gene expressed efficiently and took up to approximant 50% of total protein by SDS-PAGE and band scanning analysis. The purified protein exhibited the identified activity through biochemical test and mouse toxicological test. As a result, the acquired ADH2 gene was highly homology to the published sequence and expressed at a high level in E. coli BL21 (DE3), more importantly, ADH2 proved to have ethanol dehydrogenase activity.