bluuebunny/crossref_metadata_2025_split huggingface dataset:
Power, Faith, and Pictures: Frans Hogenberg’s Account of the Beeldenstorm
Authors: Voges Ramon 
Published: March 2016

Frans Hogenberg’s depiction of the Beeldenstorm is one of the most popular and influential visual accounts of iconoclasm. However, it has been considered controversial in Academia due to the account’s complex visual rhetoric. To tackle this complexity this contribution offers a close reading of Hogenberg’s depiction as an historical source by exploring its various references and allusions. The printed image allows historians to gain insights into the religious and political culture of the second half of the sixteenth century. This essay argues that Hogenberg’s account of the Beeldenstorm is a reflection on the power of images and its limitations. As such, the print was directly involved in the battle of how to understand contemporary religious and political conflicts. Although the account appeals to a heterogeneous audience, it depicts the Beeldenstorm in neither a neutral nor in an objective way, but from a position of religious compromise and secular unanimity. This article is part of the special issue 'Beeldenstorm' and was nominated for the Low Countries History Award in 2019 (for the best article in BMGN - Low Countries Historical Review over the years 2016-2017-2018). Macht, geloof, en afbeeldingen. Frans Hogenbergs uitbeelding van de BeeldenstormFrans Hogenbergs uitbeelding van de Beeldenstorm is een van bekendste en invloedrijkste visuele weergaven van iconoclasme. Binnen het academisch onderzoek hebben echter verhitte discussies gewoed als gevolg van de gecompliceerde visuele retoriek in de afbeelding. Om deze complexiteit te ontrafelen hanteert dit artikel een nauwkeurige lezing van de afbeelding als historische bron en onderzoekt het de verschillende verwijzingen en zinspelingen er in. De afbeelding verschaft historici de mogelijkheid inzicht te krijgen in de religieuze en politieke cultuur van de tweede helft van de zestiende eeuw. Het artikel stelt dat Hogenbergs weergave van de Beeldenstorm een reflectie is op de kracht van beelden en hun beperkingen. De gravure was als zodanig zelf onderdeel van de strijd over de vraag hoe de religieuze en politieke conflicten van die tijd moesten worden begrepen. Hoewel de afbeelding uiteenlopende toeschouwers wil aanspreken, geeft zij de Beeldenstorm niet op een neutrale of objectieve wijze weer, maar vanuit een stellingname voor een religieus compromis en seculiere eensgezindheid. Dit artikel maakt deel uit van het themanummer 'Beeldenstorm' en werd genomineerd voor de Low Countries History Award in 2019 (voor het beste artikel in BMGN - Low Countries Historical Review in 2016-2017-2018).
Accumulation and depletion of fertilizer originated nitrate-N and ammonium-N in deeper soil layers
Authors: Füleky György 
Published: March 2016

The leaching process of nitrate was studied in a long-term field experiment at Gödöllő on a brown forest soil started in 1969. 0, 90, 180, 270, 360 kg ha-1 y-1 N doses have been broadcasted as basal fertilization in the form of ammonium-nitrate for 16 years. The test plant was maize in monoculture. In autumn 1989 fertilization was discontinued and alfalfa was sown on the experimental area. In 1995 pseudoacacia was planted into the field. In 1986, 1989, 1994 and 2003 the soils of the treatments were sampled in 6 replications from 0 to 3 meters depth at every 20 cm. The nitrate-N and ammonium-N content of the sample was determined. Increasing the dose of nitrogen fertilization nitrate content in the soil profile increased, as well. About the half of fertilizer nitrogen can be found in the 3 meter layer of the soil profile after 16 years fertilization. Using deep rooting plants the accumulated nitrogen could be used to prevent the leaching losses. Results prove the necessity of a suitable technology preventing nitrate losses. As the experiment shows 100 kg N ha-1 fertilizer nitrogen enough for the maximum crop yield in this area. The amount of nitrate-N exceeding plant demand could be leached into 1-3 meter depth of soil or into deeper horizons.
A New Cytotoxic Steroidal Glycoalkaloid from the Methanol Extract of Blumea lacera Leaves
Authors: Akter Raushanara , Uddin Shaikh J. , Tiralongo Joe , Grice I. Darren , Tiralongo Evelin 
Published: March 2016

PURPOSE: Blumea lacera (B. lacera) (Asteraceae) is a well-known Bangladeshi medicinal plant. This study aimed to identify and characterize constituents associated with the significant cytotoxic activity of this plant that we reported previously. Here, we describe the isolation and characterization of a new steroidal glycoalkaloid (SGA) 1, the evaluation of its cytotoxic activity, apoptotic potential, and effect on cell cycle in comparison to analogous steroidal glycoalkaloids (SGAs). METHODS: SGA 1 was isolated using C18 SPE and HPLC, and subsequently structurally characterized using 1D and 2D NMR, MS and other spectroscopic methods, along with a comparative inspection of the literature. Cytotoxic activity of 1 and seven SGA analogues and steroidal alkaloids (SAs), (β-solamarine, α-solanine, β-solamargine, α-solasonine, khasianine, solasodine, tomatidine HCl) were evaluated for their cytotoxicity against two healthy (NIH3T3 and VERO) and four human cancer (AGS, HT-29, MCF-7 and MDA-MB-231) cell lines using the MTT assay. Cytotoxic SGAs were further evaluated for apoptosis-inducing potential and cell cycle arresting ability against breast cancer cells (MCF-7) using the FITC Annexin V and propidium iodide (PI) assay. RESULTS: Bioactivity guided fractionation of the methanol extract of B. lacera led to isolation of compound 1: (25R)-3β-{O-β-D-glucopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl-(1→2)]-α-L-rhamnopyranosyl}-22αN-spirosol-5-ene. SGA 1 was the most cytotoxic compound against a number of human cancer cell lines with an IC50 of 2.62 µM against MCF-7 cells. It displayed the highest apoptotic potential (32% AV+/PI-) on MCF-7 cells compared to other cytotoxic SGA analogues and a slight, but significant cell cycle arresting effect. CONCLUSIONS: A new SGA 1 was isolated from B. lacera and its cytotoxic activity, as well as that of other SAGs, was evaluated. SAR investigations on SGA 1, in relation to SGA analogues, show that the number and nature of sugar moieties along with the linkages of the sugar to the aglycone are crucial for cytotoxic and apoptotic activity. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Calebin A: Analytical Development for Pharmacokinetics Study, Elucidation of Pharmacological Activities and Content Analysis of Natural Health Products
Authors: Oliveira Ana Luísa De P. , Martinez Stephanie E. , Nagabushnam Kalyanam , Majeed Muhammed , Alrushaid Samaa , Sayre Casey L. , Davies Neal M. 
Published: March 2016

Purpose: To develop a bioanalytical assay using RP-HPLC to quantify the curcuminoid calebin A, to characterize its pharmacokinetics in rats after intravenous (IV) and oral (PO) administration, to identify its pharmacological activities and to evaluate its content in natural health products. Methods: An RP-HPLC method was developed for the detection of calebin A. Separation was carried out using a Phenomenex® Kinetex® C18 column with UV detection at 339 nm. An isocratic mobile phase consisting of acetonitrile and water with 10 mM ammonium formate (pH 7.0) (40:60, v/v) at a flow rate of 0.8 mL/min was employed. Linear standard curves were established and applied in the pharmacokinetic study. Calebin A was administered to male Sprague-Dawley (CD) rats IV (20 mg/kg) or PO (500 mg/kg) (n=4/route of administration). Serum and urine samples were collected for 72 h post dose. In vitro antioxidant activity, anti-inflammatory activity (cyclooxygenase and lipoxygenase inhibition), dipeptidyl peptidase-4 (DPP-4) inhibition and cytochrome P450 inhibitory activties of calebin A were examined using commercial assay kits. Content analysis of calebin A in 14 natural health products advertised to contain turmeric were carried out using methanolic extraction. Results: The HPLC method was successfully applied to a pharmacokinetic study of calebin A in rats. After IV and PO administration of calebin A, the compound was detected as the aglycone and a glucuronidated metabolite. Oral bioavailabitily was found to be ~0.5%, serum half-life was ~1-3 h. Calebin A appears to be primarily excreted via non-renal routes. Calebin A possessed concentration-dependent antioxidant activity and DPP-4 inhibition. Calebin A appears to be a non-selective cyclooxygenase inhibitor and also a poor lipoxygenase inhibitor. The curcuminoid displayed in vitro interactions with CYP2D6 and CYP1A2. Content analysis of 14 natural health products that claimed to contain turmeric showed that concentration of calebin A was inconsistent among the products. Conclusion: A successful assay was developed for the detection of calebin A using RP-HPLC. Preliminary pharmacokinetic studies indicate that an unoptimised formulation of calebin A has poor oral bioavailability. Calebin A exhibits various pharmacological activities. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Reversible, Time-Dependent Inhibition of CYP3A-Mediated Metabolism of Midazolam and Tacrolimus by Telaprevir in Human Liver Microsomes
Authors: Chapron Brian , Risler Linda , Phillips Brian , Collins Carol , Thummel Kenneth , Shen Danny 
Published: March 2016

Purpose Telaprevir inhibits CYP3A resulting in drug-drug interactions (DDI) of unprecedented magnitude. We investigated the mechanisms by which telaprevir inhibits the oxidation of midazolam and tacrolimus in human liver microsomes (HLM). Methods We performed a static mechanistic DDI prediction to evaluate whether previously reported competitive inhibition of CYP3A by telaprevir and its diastereomeric metabolite ― VRT-127394 is sufficient to explain the remarkable reduction in oral clearance observed with oral midazolam and tacrolimus. To further explore the inhibitory mechanisms of telaprevir, we assessed whether telaprevir-mediated inhibition of the oxidation of midazolam and tacrolimus is time-dependent in human liver microsomes, and whether any observed time-dependency was irreversible or reversible in nature. Results The competitive inhibition model failed to account for the magnitude of telaprevir interactions in human subjects. In comparing HLM incubations with and without a prior 30-min exposure to telaprevir, a respective 4- and 11-fold reduction in IC50 was observed with midazolam and tacrolimus as substrates. This time-dependent inhibition was shown to be NADPH-dependent. Upon dilution of microsomes following pre-incubation with telaprevir, time-dependent inhibition of midazolam metabolism was completely reversed, whereas partial reversal occurred with tacrolimus. Conclusions The interaction between telaprevir and midazolam or tacrolimus involves both competitive and time-dependent inhibition. The time-dependent component is not explained by irreversible inactivation of CYP3A. Formation of potent inhibitory metabolites may contribute to the remarkable in vivo inhibitory potency of telaprevir. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Nonclassical Biological Activities of Quinolone Derivatives
Authors: Daneshtalab Mohsen , Ahmed Abeer 
Published: March 2016

Quinolones are considered as a big family of multi-faceted drugs; their chemical synthesis is flexible and can be easily adapted to prepare new congeners with rationally devised structures. This is shown by the description of many thousands of derivatives in the literature. Scientists could accurately describe their QSAR, which is essential for effective drug design. This also gave them the chance to discover new and unprecedented activities, which makes quinolones an endless source of hope and enables further development of new clinically useful drugs.
Quinolones are among the most common frameworks present in the bioactive molecules that have dominated the market for more than four decades. Since 1962, 4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial agents. Quinolones have a broad and potent spectrum of activity and are also used as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been reported to display “nonclassical” biological activities, such as antitumor, anti-HIV-1 integrase, anti- HCV-NS3 helicase and -NS5B-polymerase activities.
The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent and/or an antiviral agent. Indeed, quinolones’ antimicrobial action is distinguishable among antibacterial agents, because they target different type II topoisomerase enzymes. Many derivatives of this family show high activity against bacterial topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured mammalian cells and in vivo tumor models. Moreover, quinolones have shown antiviral activity against HIV and HCV viruses. In this context the quinolones family of drugs seem to link three different biological activities (antibacterial, anticancer, and the antiviral profiles) and the review will also provide an insight into the different mechanisms responsible for these activities among different species.

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Pharmacologic Activities¬ of 3’-Hydroxypterostilbene: Cytotoxic, Anti-Oxidant, Anti-Adipogenic, Anti-Inflammatory, Histone Deacetylase and Sirtuin 1 Inhibitory Activity
Authors: Takemoto Jody K , Remsberg Connie M. , Davies Neal M. 
Published: March 2016

Purpose: Delineate the selected pharmacodynamics of a naturally occurring stilbene 3’-Hydroxypterostilbene. Objective: Characterize for the first time the pharmacodynamics bioactivity in several in-vitro assays with relevant roles in heart disease, inflammation, cancer, and diabetes etiology and pathophysiology. Methods: 3’-Hydroxypterostilbene was studied in in-vitro assays to identify possible bioactivity. Results: 3’-Hydroxypterostilbene demonstrated anti-oxidant, anti-inflammatory, cytotoxic, anti-adipogenic, histone deacetylase, and sirtuin-1 inhibitory activity. Conclusions: The importance of understanding individual stilbene pharmacologic activities were delineated. Small changes in chemical structure of stilbene compounds result in significant pharmacodynamic differences. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Statins Reduce Mortality After Non-severe but Not After Severe Pneumonia: A Systematic Review and Meta-Analysis
Authors: Jia Mingwang , Huang Wenjie , Li Li , Xu Zhong , Wu Lichan 
Published: March 2016

PURPOSE: The objective of this study was to perform a systematic review and meta-analysis of the effects of statins on mortality for patients with non-severe pneumonia or severe pneumonia. METHODS: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane central register of controlled trials and Clinicaltrials.gov were searched for the association between statins and non-severe/severe pneumonia. Eligible articles were analyzed in Stata 12.0. RESULTS: The database search yielded a total of 566 potential publications, 24 studies involving 312,309 patients met the eligibility criteria. Pooled unadjusted data showed that statin use was associated with lower mortality after non-severe pneumonia (odds ratio [OR] 0.70, 95% confidence interval [CI], 0.66-0.73), but not severe pneumonia (OR 1.05; 95% CI, 0.86-1.28). However, this protective effect of statins was weakened using adjusted estimates (OR 0.78, 95% CI, 0.75-0.82). Besides, protective effect of statins was attenuated by confounders in a subgroup analysis, especially when accounting for pneumonia severity indicators (OR 0.88; 95% CI, 0.80-0.96). CONCLUSIONS: Statin use was associated with reduced mortality after non-severe pneumonia but not severe pneumonia and this protective effect was weakened in subgroups. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic
Authors: Maini Sabia , Fahlman Brian M. , Krol Ed S. 
Published: March 2016

Purpose: Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. Methods: EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m2 at 365 nm) and UVB (9000 J/m2 at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. Results: EpiDerm ™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Conclusions: Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
A Simple Method to Extract Whole Apolipoproteins for the Preparation of Discoidal Recombined High Density Lipoproteins as Bionic Nanocarriers for Drug Delivery
Authors: Zhang Wenli , Wang Ji , Jia Junting , Chen Liang , Wu Zimei , Liu Jianping 
Published: March 2016

Purpose: To develop a simple method to extract the whole apolipoproteins (apo) including apoA-I in native high density lipoproteins (HDLs) and prepare discoidal Tanshinone IIA-loaded reconstituted HDL (TA-rHDLs) as a dual functional drug delivery system with plaque-site target and therapeutic promises in atherosclerotic lesions. Methods: A method based on isoelectric precipitation coupled with organic solvent precipitation was developed to isolate the whole apolipoproteins (apos). TA-rHDLs were prepared by incubating the resultant apos with liposomes and the incubation conditions were optimized using fluorescence quenching experiment. TA-rHDLs were characterized in terms of size, zeta potential, morphology, interaction between lipid and apos, safety, and bionic function. Results: The extraction results showed that the yield of the HDL apos was 82.4%, with 59% being apoA-I type, similar ratio of apoA-I in the native apos. TA-rHDL prepared were disc-like with an average diameter of 157.6 ± 4.8 nm, zeta potential of -20.90 ± 0.15 mV, and entrapment efficiency of (90.13 ± 1.4) %. The interaction between the lipids and apos was electrostatic and hydrophobic force and was associated with amino acid sequence. Haemolysis and cytotoxicity assays showed good biocompatibility of TA-rHDL. Sterol efflux assay from macrophages mediated by TA-rHDLs and structure remodeling behavior from discs to spheres proved that TA-rHDL could resemble the biological activity of native nascent HDL irrespective of the size. Conclusions: The simple approach to isolate apos may provide a convenient and economical resource to support the development of rHDL as a potential targeting nanocarrier for lipophilic cardiovascular drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Effect of Terpenes on the Skin Permeation of Lomerizine Dihydrochloride
Authors: Furuishi Takayuki , Kato Yukiko , Fukami Toshiro , Suzuki Toyofumi , Endo Tomohiro , Nagase Hiromasa , Ueda Haruhisa , Tomono Kazuo 
Published: March 2016

Purpose. Lomerizine dihydrochloride (LOM) is a Ca2+ channel blocker used as an antimigraine drug, which is currently administered orally in Japan. We therefore investigated the effect of terpenes in propylene glycol (PG) solvent on the percutaneous absorption of LOM by hairless mouse skin. Methods. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), confocal laser scanning microscopy (CLSM), and small angle X-ray scattering (SAXS) were carried out to analyze the effects of terpene enhancers on the biophysical properties of the stratum corneum (SC) of the skin. Results. Of the terpenes tested, the highest permeation rate of LOM (28.8 mg/cm2/h) was observed with 1,8-cineole, while nerolidol conferred the lowest enhancement of LOM flux (14.2 mg/cm2/h). ATR-FTIR studies revealed that terpenes/PG induced higher CH2 stretching frequencies of SC lipids than PG alone. The extent of penetration of the lipophilic fluorescence probes Nile Red and DiI was measured by CLSM in in vitro skin permeation studies, using either PG or terpenes/PG as skin permeation enhancers. With PG alone, both fluorescence dyes were undetectable in the skin. In contrast, when co-administered with terpenes/PG, both probes were distributed into the intercellular space between corneocytes and detected in the deeper layers of the skin. SAXS measurements showed that in SC treated with a combination of 1,8-cineole and PG, the scattering peak of the SC was broad and very weak in intensity compared to untreated SC, whereas pretreatment with PG alone did not alter the peak profile. Conclusion. A combination of terpenes and PG enhance the skin permeation of LOM. Our findings suggest that the mechanism for this effect involves the ability of terpenes to increase the fluidity of SC lipids, thus enhancing the distribution of LOM into the intercellular region of the SC. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Phyto-Extracts in Wound Healing
Authors: Ghosh Prasanta Kumar , Gaba Anjali 
Published: March 2016

Data generated through systematic investigation, carried out on the evaluation of phyto-extracts on wound healing research during the last 20 years have been compiled. About 450 plant species having wound healing properties have been identified. The present knowledge of the wound healing process comprise coagulation, inflammation, proliferation, formation and accumulation of fibrous tissues, collagen deposition, epithelialization, contraction of wound with formation of granulation tissues, remodeling and maturation. The constituents of the plant extracts modulate one or more of the above stages. It was the endeavor to identify the active constituents responsible for antimicrobial activity, free radical scavenging properties, stimulators of enhanced collagen production and/or angiogenesis promoters with identification of lead scaffold chemical structures. Multiple phytochemicals concentrated and blended in optimal concentrations, are expected to be available in future years to carry out multi-tasking efforts in wound healing as more knowledge about the properties of the key constituents are unveiled.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.