bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of Porphyrins and Their Analogues for Inactivation of Viruses
Authors: Lebedeva Natalya Sh. , Gubarev Yury A. , Koifman Mikhail O. , Koifman Oskar I.
Published: September 2020

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas.
Distinct Influence of Hypercaloric Diets Predominant with Fat or Fat and Sucrose on Adipose Tissue and Liver Inflammation in Mice
Authors: Fonseca Caíque S. M. , Basford Joshua E. , Kuhel David G. , Konaniah Eddy S. , Cash James G. , Lima Vera L. M. , Hui David Y.
Published: September 2020

Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.
Constituents of Coreopsis lanceolata Flower and Their Dipeptidyl Peptidase IV Inhibitory Effects
Authors: Kim Bo-Ram , Paudel Sunil , Nam Joo-Won , Jin Chang , Lee Ik-Soo , Han Ah-Reum
Published: September 2020

A new polyacetylene glycoside, (5R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-β-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and (3S,4S)-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2′-dihydroxy-4-3′-dimethoxychalcone-4′-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2–4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 μM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.
Comparative Phytochemical, Antioxidant, and Hemostatic Studies of Extract and Four Fractions from Paulownia Clone in Vitro 112 Leaves in Human Plasma
Authors: Adach Weronika , Żuchowski Jerzy , Moniuszko-Szajwaj Barbara , Szumacher-Strabel Malgorzata , Stochmal Anna , Olas Beata , Cieslak Adam
Published: September 2020

Background: The Paulownia Clone in Vitro 112, known as oxytree or oxygen tree, is a hybrid clone of the species Paulownia elongata and Paulownia fortunei (Paulowniaceae). The oxytree is a fast-growing hybrid cultivar that can adapt to wide variations in edaphic and climate conditions. In this work, Paulownia Clone in Vitro 112 leaves were separated into an extract and four fractions (A–D) differing in chemical content in order to investigate their chemical content using LC-MS analysis. The extract and fractions were also evaluated for their anticoagulant and antioxidant properties in a human plasma in vitro. Results: The Paulownia leaf extract contained mainly phenolic compounds (e.g., verbascoside), small amounts of iridoids (e.g., aucubin or 7-hydroxytometoside) and triterpenoids (e.g., maslinic acid) were also detected. Our results indicate that the extract and fractions have different effects on oxidative stress in human plasma treated with H2O2/Fe in vitro, which could be attributed to differences in their chemical content. For example, the extract and all the fractions, at the two highest concentrations of 10 and 50 µg/mL, significantly inhibited the plasma lipid peroxidation induced by H2O2/Fe. Fractions C and D, at all tested concentrations (1–50 µg/mL) were also found to protect plasma proteins against H2O2/Fe-induced carbonylation. The positive effects of fraction C and D were dependent on the dose. Conclusions: The extract and all four fractions, but particularly fractions C and D, which are rich in phenolic compounds, are novel sources of antioxidants, with an inhibitory effect on oxidative stress in human plasma in vitro. Additionally, the antioxidant potential of fraction D may be associated with triterpenoids.
Development and Validation of an LC-MS/MS Assay to Quantitate 2′,4′,6′-Trihydroxyacetophenone in Rat and Dog Plasma and its Application to a Pharmacokinetic Study
Authors: Yoo Hee Jo , Hwang Se-Jung , Lee Jeong-Hun , Shim Wang-Seob , Choi Yun-Woong , Cho Sang Min , Chung Eun Kyoung , Park Jun-Bom , Lee Kyung-Tae
Published: September 2020

In the present study, a simple, rapid, and reliable bioanalytical method was developed using liquid chromatography with tandem-mass spectrometry (LC-MS/MS) to quantify 2′,4′,6′-trihydroxyacetophenone (THAP) in rat and dog plasma with 2′,4′,6′-trihydroxybenzaldehyde as an internal standard (IS). The LC-MS/MS instrument was operated in the multiple reaction monitoring (MRM) mode to detect THAP at m/z transition 166.89 > 82.8 and IS at 152.89 > 82.8, respectively. A simple, one-step protein precipitation (PP) method was employed with acetonitrile for sample preparation. Utilizing a Gemini C18 column, THAP and IS were separated with an isocratic mobile phase consisting of 10 mM ammonium acetate and methanol (10:90, v/v) at a flow rate of 0.2 mL/min. Total chromatographic run time was 2.5 min per sample injection. The standard calibration curve for THAP was linear (r2 ≥ 0.9987) over the concentration range of 0.1 to 100 µg/mL with the lower limit of quantitation (LLOQ) of 0.1 µg/mL (S/N ratio > 10). According to the regulatory guidelines from the U.S. Food and Drug Administration (FDA) and the Korea Ministry of Food and Drug Safety (MFDS), our newly developed biomedical analytical method was fully and adequately validated in terms of selectivity, sensitivity, linearity, intra- and inter-day precision and accuracy, recovery, matrix effect, stability, and dilution integrity. Our validated assay was successfully utilized in a nonclinical pharmacokinetic study of THAP in rats and dogs.
Novel Harmicines with Improved Potency against Plasmodium
Authors: Marinović Marina , Perković Ivana , Fontinha Diana , Prudêncio Miguel , Held Jana , Pessanha de Carvalho Lais , Tandarić Tana , Vianello Robert , Zorc Branka , Rajić Zrinka
Published: September 2020

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.
Water-Soluble Bismuth(III) Polynuclear Tyrosinehydroximate Metallamacrocyclic Complex: Structural Parallels to Lanthanide Metallacrowns
Authors: Katkova Marina A. , Zhigulin Grigory Y. , Rumyantcev Roman V. , Zabrodina Galina S. , Shayapov Vladimir R. , Sokolov Maxim N. , Ketkov Sergey Y.
Published: September 2020

Recently there has been a great deal of interest and associated research into aspects of the coordination chemistry of lanthanides and bismuth—elements that show intriguing common features. This work focuses on the synthesis and characterization of a novel bismuth(III) polynuclear metallamacrocyclic complex derived from aminohydroxamic acid, in order to compare the coordination ability of Bi3+ with the similarly sized La3+ ions. A polynuclear tyrosinehydroximate Bi(OH)[15-MCCu(II)Tyrha-5](NO3)2 (1) was obtained according to the synthetic routes previously described for water-soluble Ln(III)-Cu(II) 15-MC-5 metallacrowns. Correlations between structural parameters of Bi(III) and Ln(III) complexes were analyzed. DFT calculations confirmed the similarity between molecular structures of the model bismuth(III) and lanthanum(III) tyrosinehydroximate 15-metallacrowns-5. Analysis of the electronic structures revealed, however, stronger donor-acceptor interactions between the central ion and the metallamacrocycle in the case of the lanthanum analogue. Thermochromic properties of 1 were studied.
Is It Conjugated or Not? The Theoretical and Experimental Electron Density Map of Bonding in p-CH3CH2COC6H4-C≡C-C≡C-p-C6H4COCH3CH2
Authors: Starynowicz Przemysław , Berski Sławomir , Gulia Nurbey , Osowska Karolina , Lis Tadeusz , Szafert Sławomir
Published: September 2020

The electron density of p-CH3CH2COC6H4-C≡CC≡C-p-C6H4COCH3CH2 has been investigated on the basis of single-crystal X-ray diffraction data collected to high resolution at 100 K and from theoretical calculations. An analysis of the X-ray data of the diyne showed interesting “liquidity” of electron distribution along the carbon chain compared to 1,2-diphenylacetylene. These findings are compatible with the results of topological analysis of Electron Localization Function (ELF), which has also revealed a larger (than expected) concentration of the electron density at the single bonds. Both methods indicate a clear π-type or “banana” character of a single bond and a significant distortion from the typical conjugated structure of the bonding in the diyne with a small contribution of cumulenic structures.
Diversity of Ginsenoside Profiles Produced by Various Processing Technologies
Authors: Piao Xiang Min , Huo Yue , Kang Jong Pyo , Mathiyalagan Ramya , Zhang Hao , Yang Dong Uk , Kim Mia , Yang Deok Chun , Kang Se Chan , Wang Ying Ping
Published: September 2020

Ginseng is a traditional medicinal herb commonly consumed world-wide owing to its unique family of saponins called ginsenosides. The absorption and bioavailability of ginsenosides mainly depend on an individual’s gastrointestinal bioconversion abilities. There is a need to improve ginseng processing to predictably increase the pharmacologically active of ginsenosides. Various types of ginseng, such as fresh, white, steamed, acid-processed, and fermented ginsengs, are available. The various ginseng processing methods produce a range ginsenoside compositions with diverse pharmacological properties. This review is intended to summarize the properties of the ginsenosides found in different Panax species as well as the different processing methods. The sugar moiety attached to the C–3, C–6, or C–20 deglycosylated to produce minor ginsenosides, such as Rb1, Rb2, Rc, Rd→Rg3, F2, Rh2; Re, Rf→Rg1, Rg2, F1, Rh1. The malonyl-Rb1, Rb2, Rc, and Rd were demalonylated into ginsenoside Rb1, Rb2, Rc, and Rd by dehydration. Dehydration also produces minor ginsenosides such as Rg3→Rk1, Rg5, Rz1; Rh2→Rk2, Rh3; Rh1→Rh4, Rk3; Rg2→Rg6, F4; Rs3→Rs4, Rs5; Rf→Rg9, Rg10. Acetylation of several ginsenosides may generate acetylated ginsenosides Rg5, Rk1, Rh4, Rk3, Rs4, Rs5, Rs6, and Rs7. Acid processing methods produces Rh1→Rk3, Rh4; Rh2→Rk1, Rg5; Rg3→Rk2, Rh3; Re, Rf, Rg2→F1, Rh1, Rf2, Rf3, Rg6, F4, Rg9. Alkaline produces Rh16, Rh3, Rh1, F4, Rk1, ginsenoslaloside-I, 20(S)-ginsenoside-Rh1-60-acetate, 20(R)-ginsenoside Rh19, zingibroside-R1 through hydrolysis, hydration addition reactions, and dehydration. Moreover, biological processing of ginseng generates the minor ginsenosides of Rg3, F2, Rh2, CK, Rh1, Mc, compound O, compound Y through hydrolysis reactions, and synthetic ginsenosides Rd12 and Ia are produced through glycosylation. This review with respect to the properties of particular ginsenosides could serve to increase the utilization of ginseng in agricultural products, food, dietary supplements, health supplements, and medicines, and may also spur future development of novel highly functional ginseng products through a combination of various processing methods.
Laser-Induced Biochar Formation through 355 nm Pulsed Laser Irradiation of Wood, and Application to Eco-Friendly pH Sensors
Authors: Jeong Sung-Yeob , Lee Chan-Woo , Lee Jun-Uk , Ma Yong-Won , Shin Bo-Sung
Published: September 2020

Due to the limited availability of agricultural land, pH sensing is becoming more and more important these days to produce efficient agricultural products. Therefore, to fabricate eco-friendly and disposable sensors, the black carbon, which is called biochar, is formed by irradiation of a UV pulsed laser having a wavelength of 355 nm onto wood and applying the resulting material as a pH sensor. The surfaces of three types of wood (beech, cork oak, and ash) were converted to the graphitic structure after UV laser irradiation; their morphologies were investigated. In addition, since the content of lignin, an organic polymer, is different for each wood, optimal laser irradiation conditions (laser fluence) needed to form these woods into pH sensors were considered. Depending on the degree of oil-like material generated after laser irradiation, a disposable pH sensor that can be used from one to three times is fabricated; due to the environmental characteristics of wood and biochar, the sensor shows high availability in that it can be easily discarded after use on agricultural land. After that, it can be used as filter in soil. Our wood-based pH sensor sensitively measures sequential changes from pH 4 to pH 10 and shows a very linear change of △R/R, indicating its potential for use in agriculture.
Toward Multi-Functional Road Surface Design with the Nanocomposite Coating of Carbon Nanotube Modified Polyurethane: Lab-Scale Experiments
Authors: Yum Sang-Guk , Yin Huiming , Jang Sung-Hwan
Published: September 2020

A novel multi-functional road surface system is designed to improve safety, the efficiency of traffic flow, and environmental sustainability for future transportation systems. The surface coating, preforming temperature detection with heating element and hydrophobic features, were fabricated with a nanocomposite consisting of carbon nanotube (CNT) modified polyurethane (PU). The CNT/PU coating showed higher electrical conductivity as well as enhanced hydrophobic properties as the CNT concentration increased. The multifunctional properties of CNT/PU coatings were investigated for use in freezing temperature sensing and heating. The CNT/PU coatings showed high temperature sensitivity in the freezing temperature range with a negative temperature coefficient of resistance. In addition, the CNT/PU coatings had excellent heating performance due to the Joule heating effect. Therefore, the proposed CNT/PU coatings are promising for use as multifunctional road coating materials for detection of freezing temperature and deicing by self-heating.
Anthocyanins in Whole Grain Cereals and Their Potential Effect on Health
Authors: Francavilla Alyssa , Joye Iris J.
Published: September 2020

Coloured (black, purple, blue, red, etc.) cereal grains, rich in anthocyanins, have recently gained a lot of attention in the food industry. Anthocyanins are water-soluble flavonoids, and are responsible for red, violet, and blue colours in fruits, vegetables, and grains. Anthocyanins have demonstrated antioxidant potential in both in vitro and in vivo studies, and the consumption of foods high in anthocyanins has been linked to lower risks of chronic diseases. As such, whole grain functional foods made with coloured grains are promising new products. This paper will review the characteristics of cereal anthocyanins, and assess their prevalence in various commercially relevant crops including wheat, barley, maize, and rice. A brief overview of the antioxidant potential, and current research on the health effects of cereal-based anthocyanins will be provided. Finally, processing of coloured cereals in whole grain products will be briefly discussed. A full understanding of the fate of anthocyanins in whole grain products, and more research targeted towards health outcomes of anthocyanin supplementation to/inclusion in cereal food products are the next logical steps in this research field.
Short Communication: Oral Administration of Heat-killed Lactobacillus brevis KB290 in Combination with Retinoic Acid Provides Protection against Influenza Virus Infection in Mice
Authors: Satomi Shohei , Khanum Sofia , Miller Poppy , Suzuki Shigenori , Suganuma Hiroyuki , Heiser Axel , Gupta Sandeep K
Published: September 2020

Influenza virus type A (IAV) is a seasonal acute respiratory disease virus with severe symptoms, and an effective preventive measure is required. Despite many reports describing the potentially protective effects of lactic acid bacteria, few studies have investigated the effects of nutritional supplement combinations. This study reports the effect of the combined intake of heat-killed Lactobacillus brevis KB290 (KB290) and vitamin A (VA) on mice challenged with a sublethal dose of IAV. For 2 weeks, five groups of mice were fed either placebo, KB290, VA, or a combination of KB290 and VA (KB290+VA). After subsequent IAV challenge, bodyweight and general health were monitored for up to 2 weeks. Viral titres were determined in the lungs of animal subgroups euthanised at days 3, 7, and 14 after IAV challenge. A significant loss was observed in the bodyweights of IAV-infected animals from day 1 post-IAV challenge, whereas the mice fed KB290+VA did not lose any weight after IAV infection, indicating successful protection from the infection. Additionally, mice in the KB290+VA group showed the highest reduction in lung viral titres. In conclusion, the combination of KB290 and VA could be a useful food supplement relevant for protection against seasonal influenza virus infection in humans.
Infectious Bronchitis Coronavirus Infection in Chickens: Multiple System Disease with Immune Suppression
Authors: M. Najimudeen Shahnas , H. Hassan Mohamed S. , C. Cork Susan , Abdul-Careem Mohamed Faizal
Published: September 2020

In the early 1930s, infectious bronchitis (IB) was first characterized as a respiratory disease in young chickens; later, the disease was also described in older chickens. The etiology of IB was confirmed later as being due to a coronavirus: the infectious bronchitis virus (IBV). Being a coronavirus, IBV is subject to constant genome change due to mutation and recombination, with the consequence of changing clinical and pathological manifestations. The potential use of live attenuated vaccines for the control of IBV infection was demonstrated in the early 1950s, but vaccine breaks occurred due to the emergence of new IBV serotypes. Over the years, various IBV genotypes associated with reproductive, renal, gastrointestinal, muscular and immunosuppressive manifestations have emerged. IBV causes considerable economic impacts on global poultry production due to its pathogenesis involving multiple body systems and immune suppression; hence, there is a need to better understand the pathogenesis of infection and the immune response in order to help developing better management strategies. The evolution of new strains of IBV during the last nine decades against vaccine-induced immune response and changing clinical and pathological manifestations emphasize the necessity of the rational development of intervention strategies based on a thorough understanding of IBV interaction with the host.
Efficient Non-Viral Gene Modification of Mesenchymal Stromal Cells from Umbilical Cord Wharton’s Jelly with Polyethylenimine
Authors: Ramos-Murillo Ana Isabel , Rodríguez Elizabeth , Beltrán Karl , Ricaurte Cristian , Camacho Bernardo , Salguero Gustavo , Godoy-Silva Rubén Darío
Published: September 2020

Mesenchymal stromal cells (MSC) derived from human umbilical cord Wharton’s jelly (WJ) have a wide therapeutic potential in cell therapy and tissue engineering because of their multipotential capacity, which can be reinforced through gene therapy in order to modulate specific responses. However, reported methodologies to transfect WJ-MSC using cationic polymers are scarce. Here, WJ-MSC were transfected using 25 kDa branched- polyethylenimine (PEI) and a DNA plasmid encoding GFP. PEI/plasmid complexes were characterized to establish the best transfection efficiencies with lowest toxicity. Expression of MSC-related cell surface markers was evaluated. Likewise, immunomodulatory activity and multipotential capacity of transfected WJ-MSC were assessed by CD2/CD3/CD28-activated peripheral blood mononuclear cells (PBMC) cocultures and osteogenic and adipogenic differentiation assays, respectively. An association between cell number, PEI and DNA content, and transfection efficiency was observed. The highest transfection efficiency (15.3 ± 8.6%) at the lowest toxicity was achieved using 2 ng/μL DNA and 3.6 ng/μL PEI with 45,000 WJ-MSC in a 24-well plate format (200 μL). Under these conditions, there was no significant difference between the expression of MSC-identity markers, inhibitory effect on CD3+ T lymphocytes proliferation and osteogenic/adipogenic differentiation ability of transfected WJ-MSC, as compared with non-transfected cells. These results suggest that the functional properties of WJ-MSC were not altered after optimized transfection with PEI.
Photostability Testing of a Third-Generation Retinoid—Tazarotene in the Presence of UV Absorbers
Authors: Kryczyk-Poprawa Agata , Zupkó István , Bérdi Péter , Żmudzki Paweł , Popiół Justyna , Muszyńska Bożena , Opoka Włodzimierz
Published: September 2020

Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography–tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2H-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. In silico studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2H-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations.
PLGA Based Drug Carrier and Pharmaceutical Applications: The Most Recent Advances
Authors: Loureiro Joana Angélica , Pereira Maria Carmo
Published: September 2020

Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful polymers that has been used to produce medicines, such as drug carriers (DC) [...]
Physiologically-Based Pharmacokinetic (PBPK) Modeling Providing Insights into Fentanyl Pharmacokinetics in Adults and Pediatric Patients
Authors: Kovar Lukas , Weber Andreas , Zemlin Michael , Kohl Yvonne , Bals Robert , Meibohm Bernd , Selzer Dominik , Lehr Thorsten
Published: September 2020

Fentanyl is widely used for analgesia, sedation, and anesthesia both in adult and pediatric populations. Yet, only few pharmacokinetic studies of fentanyl in pediatrics exist as conducting clinical trials in this population is especially challenging. Physiologically-based pharmacokinetic (PBPK) modeling is a mechanistic approach to explore drug pharmacokinetics and allows extrapolation from adult to pediatric populations based on age-related physiological differences. The aim of this study was to develop a PBPK model of fentanyl and norfentanyl for both adult and pediatric populations. The adult PBPK model was established in PK-Sim® using data from 16 clinical studies and was scaled to several pediatric subpopulations. ~93% of the predicted AUClast values in adults and ~88% in pediatrics were within 2-fold of the corresponding value observed. The adult PBPK model predicted a fraction of fentanyl dose metabolized to norfentanyl of ~33% and a fraction excreted in urine of ~7%. In addition, the pediatric PBPK model was used to simulate differences in peak plasma concentrations after bolus injections and short infusions. The novel PBPK models could be helpful to further investigate fentanyl pharmacokinetics in both adult and pediatric populations.
Direct Quantification of Drug Loading Content in Polymeric Nanoparticles by Infrared Spectroscopy
Authors: Carissimi Guzmán , Montalbán Mercedes G. , Víllora Gloria , Barth Andreas
Published: September 2020

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision, and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89% of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. The results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0%, respectively. The method’s robustness is demonstrated by the notable similarities between the calibrations carried out using two different equipment setups at two different institutions.
Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa
Authors: Anasagasti Ander , Lara-López Araceli , Milla-Navarro Santiago , Escudero-Arrarás Leire , Rodríguez-Hidalgo María , Zabaleta Nerea , González Aseguinolaza Gloria , de la Villa Pedro , Ruiz-Ederra Javier
Published: September 2020

Inherited retinal dystrophies (IRDs) are a group of rare retinal conditions, including retinitis pigmentosa (RP), caused by monogenic mutations in 1 out of more than 250 genes. Despite recent advancements in gene therapy, there is still a lack of an effective treatment for this group of retinal conditions. MicroRNAs (miRNAs) are a class of highly conserved small non-coding RNAs that inhibit gene expression. Control of miRNAs-mediated protein expression has been described as a widely used mechanism for post-transcriptional regulation in many physiological and pathological processes in different organs, including the retina. Our main purpose was to test the hypothesis that modulation of a group of miRNAs can protect photoreceptor cells from death in the rd10 mouse model of retinitis pigmentosa. For this, we incorporated modulators of three miRNAs in adeno-associated viruses (AAVs), which were administered through sub-retinal injections. The results obtained indicate that inhibition of the miR-6937-5p slows down the visual deterioration of rd10 mice, reflected by an increased electroretinogram (ERG) wave response under scotopic conditions and significant preservation of the outer nuclear layer thickness. This work contributes to broadening our knowledge on the molecular mechanisms underlying retinitis pigmentosa and supports the development of novel therapeutic approaches for RP based on miRNA modulation.
Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
Authors: Borrego-Sánchez Ana , Sánchez-Espejo Rita , García-Villén Fátima , Viseras César , Sainz-Díaz C. Ignacio
Published: September 2020

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained.
Global Trends in Phytohormone Research: Google Trends Analysis Revealed African Countries Have Higher Demand for Phytohormone Information
Authors: Mohanta Tapan Kumar , Mohanta Yugal Kishore , Yadav Dhananjay , Hashem Abeer , Abd_Allah Elsayed Fathi , Al-Harrasi Ahmed
Published: September 2020

The lines of research conducted within a country often reflect its focus on current and future economic needs. Analyzing “search” trends on the internet can provide important insight into predicting the direction of a country in regards to agriculture, health, economy, and other areas. ‘Google Trends’ collects data on search terms from different countries, and this information can be used to better understand sentiments in different countries and regions. Agricultural output is responsible for feeding the world and there is a continuous quest to find ways to make agriculture more productive, safe, and reliable. The application of phytohormones has been used in agriculture world-wide for many years to improve crop production and continues to be an active area of research for the application in plants. Therefore, in the current study, we searched ‘Google Trends’ using the phytohormone search terms, abscisic acid, auxins, brassinosteroids, cytokinin, ethylene, gibberellins, jasmonic acid, salicylic acid, and strigolactones. The results indicated that the African country Zambia had the greatest number of queries on auxin research, and Kenya had the most queries in cytokinin and gibberellin research world-wide. For other phytohormones, India had the greatest number of queries for abscisic acid and South Korea had the greatest number of ethylene and jasmonic acid search world-wide. Queries on salicylic acid have been continuously increasing while the least number of queries were related to strigolactones. Only India and United States of America had significant numbers of queries on all nine phytohormones while queries on one or more phytohormones were absent in other countries. India is one of the top five crop-producing countries in the world for apples, millet, orange, potato, pulses, rice, sugarcane, tea, and wheat. Similarly, the United States of America is one of the top five crop-producing countries of the world for apples, grapes, maze, orange, potato, sorghum, sugarcane, and wheat. These might be the most possible factors for the search queries found for all the nine phytohormones in India and the United States of America.
Responses to Increased Salinity and Severe Drought in the Eastern Iberian Endemic Species Thalictrum maritimum (Ranunculaceae), Threatened by Climate Change
Authors: González-Orenga Sara , Trif Calin , Donat-Torres Mͣ Pilar , Llinares Josep V. , Collado Francisco , Ferrer-Gallego P. Pablo , Laguna Emilio , Boscaiu Monica , Vicente Oscar
Published: September 2020

Thalictrum maritimum is an endangered, endemic species in East Spain, growing in areas of relatively low salinity in littoral salt marshes. A regression of its populations and the number of individuals has been registered in the last decade. This study aimed at establishing the causes of this reduction using a multidisciplinary approach, including climatic, ecological, physiological and biochemical analyses. The climatic data indicated that there was a direct negative correlation between increased drought, especially during autumn, and the number of individuals censused in the area of study. The susceptibility of this species to water deficit was confirmed by the analysis of growth parameters upon a water deficit treatment applied under controlled greenhouse conditions, with the plants withstanding only 23 days of complete absence of irrigation. On the other hand, increased salinity does not seem to be a risk factor for this species, which behaves as a halophyte, tolerating in controlled treatments salinities much higher than those registered in its natural habitat. The most relevant mechanisms of salt tolerance in T. maritimum appear to be based on the control of ion transport, by (i) the active transport of toxic ions to the aerial parts of the plants at high external salinity—where they are presumably stored in the leaf vacuoles to avoid their deleterious effects in the cytosol, (ii) the maintenance of K+ concentrations in belowground and aboveground organs, despite the increase of Na+ levels, and (iii) the salt-induced accumulation of Ca2+, particularly in stems and leaves. This study provides useful information for the management of the conservation plans of this rare and endangered species.
A Plant’s Electrical Parameters Indicate Its Physiological State: A Study of Intracellular Water Metabolism
Authors: Zhang Cheng , Wu Yanyou , Su Yue , Xing Deke , Dai Yi , Wu Yansheng , Fang Lei
Published: September 2020

Almost all of a plant’s life activities involve electrochemical reactions. Plant electrical parameters respond quickly to environmental changes and are closely related to physiological activities. In this study, the theoretical intrinsic relationships between clamping force and leaf impedance (Z) or capacitive reactance (Xc) and capacitance (C) were revealed as 3-parameter exponential decay and linear models based on bioenergetics, respectively, for the first time. Leaf electrical characteristics including intrinsic impedance (IZ), capacitive reactance (IXc), capacitance (IC) and specific effective thickness (d) were successfully detected using the above-mentioned relationships and were used to manifest plant metabolic activity. The intracellular water-holding capacity (IWHC), water-use efficiency (IWUE), water-holding time (IWHT) and water transfer rate (WTR) of plant leaves were defined on the basis of IZ, IXc, IC and d, and applied to reflect the intracellular water metabolism. The results demonstrated that the leaves of Broussonetia papyrifera plants grown in agricultural soil had higher IC, d, IWHC, WTR, water content values and lower IZ, IXc values than those grown in moderately rocky desertified soil. The leaf IC, d, IWHC, WTR and water content values of herbaceous plants were higher than those of woody plants. Solanum tuberosum L. had higher leaf IC, d, IWHC and WTR values, but exhibited lower IZ, IXc, IWUE and IWHT values than Capsicum annuum L. This study highlighted that a plant’s electrical parameters based on bioenergetics clearly indicate its physiological process—e.g., the intracellular water metabolism.
Synthesis and Characterization of Ionic Graft Copolymers: Introduction and In Vitro Release of Antibacterial Drug by Anion Exchange
Authors: Niesyto Katarzyna , Neugebauer Dorota
Published: September 2020

Amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethyl- ammonium chloride (TMAMA) were obtained for the delivery of pharmaceutical ionic drugs, such as p-aminosalicylate (PAS) and clavunate (CLV) anions. The side chains were attached by grafting from a multifunctional macroinitiator via atom transfer radical polymerization (ATRP) to get polymers with different grafting degrees and ionic content. The self-assembling ability, confirmed by determining the critical micelle concentration (CMC) through interfacial tension (IFT) with the use of goniometry, was reduced after ion exchange (CMC twice higher than for chloride anions contained copolymers 0.005–0.026 mg/mL). Similarly, the hydrophilicity level (adjusted by the content of ionic fraction) evaluated by the water contact angle (WCA) of the polymer film surfaces was decreased with the increase of trimethylammonium units (68°–44°) and after introduction of pharmaceutical anions. The exchange of Cl− onto PAS− and CLV− in the polymer matrix was yielded at 31%–64% and 79%–100%, respectively. The exchange onto phosphate anions to release the drug was carried out (PAS: 20%–42%, 3.1–8.8 μg/mL; CLV: 25%–73%, 11–31 μg/mL from 1 mg of drug conjugates). Because of the bacteriostatic activity of PAS and the support of the action of the antibiotics by CLV, the designed water-soluble systems could be alternatives for the treatment of bacterial infections, including pneumonia and tuberculosis.
Preparation of Chitosan—Graphene Oxide Composite Aerogel by Hydrothermal Method and Its Adsorption Property of Methyl Orange
Authors: Zhu Wei , Jiang Xueliang , Liu Fangjun , You Feng , Yao Chu
Published: September 2020

Graphene based aerogel has become one of the most likely functional adsorption materials that is applicable to purify various contaminated water sources, such as dye wastewater, because of its high porosity, structural stability, large specific surface area, and high adsorption capacity. In this study, chitosan and graphene oxide were first selected as the matrix to prepare the composite hydrogel through the hydrothermal method, which was further frozen and dried to obtain the target aerogel. The microscopic structures and adsorption capacity of the composite aerogel were then characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and N2 (nitrogen) physical adsorption and desorption tests. The results show that the specific surface area of the composite aerogel was reached at 297.431 m2/g, which is higher than that of graphene oxide aerogel and chitosan aerogel. The aperture was reduced to about 3 nm. The adsorption rate of the composite aerogel for the methyl orange solution was as high as 97.2% at pH = 1, and the adsorption capacity was 48.6 mg/g. The adsorption process of the composite aerogel satisfies the Langmuir equation and can be described by the second-order adsorption kinetics. In addition, it is worth noting that this composite aerogel can provide a striking adsorption characteristic on methyl orange due to the combining effects from massive amino groups on chitosan and the structural conjugation of graphene oxide.
The Effect of Silica-Filler on Polyurethane Adhesives Based on Renewable Resource for Wood Bonding
Authors: Mamiński Mariusz Ł. , Więcław-Midor Anna M. , Parzuchowski Paweł G.
Published: September 2020

The aim of the study was to evaluate the applicability and performance of polyglycerol- and sucrose-based polyols as components of a simplified formulation of polyurethane adhesives. Colloidal silica was used as a viscosity control and reinforcing agent. The adhesives were examined in terms of reactivity, thermal stability, viscosity, work of adhesion, wetting, surface energy, and bonding strength on wooden substrates. Silica was found to increase gelling time, but markedly improved bonding strength and adhesion with substrates. Bonded solid beech wood samples prepared at 80, 110, and 130 °C showed shear strengths between 7.1 MPa and 9.9 MPa with 100% wood failure. The renewable resource-based polyols were demonstrated to be useful in formulation of polyurethane adhesives for furniture industry—especially with silica as a filler.
The Covalent Tethering of Poly(ethylene glycol) to Nylon 6 Surface via N,N′-Disuccinimidyl Carbonate Conjugation: A New Approach in the Fight against Pathogenic Bacteria
Authors: Swar Sumita , Máková Veronika , Stibor Ivan
Published: September 2020

Different forms of unmodified and modified Poly(ethylene glycols) (PEGs) are widely used as antifouling and antibacterial agents for biomedical industries and Nylon 6 is one of the polymers used for biomedical textiles. Our recent study focused on an efficient approach to PEG immobilization on a reduced Nylon 6 surface via N,N′–disuccinimidyl carbonate (DSC) conjugation. The conversion of amide functional groups to secondary amines on the Nylon 6 polymer surface was achieved by the reducing agent borane-tetrahydrofuran (BH3–THF) complex, before binding the PEG. Various techniques, including water contact angle and free surface energy measurements, atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy, were used to confirm the desired surface immobilization. Our findings indicated that PEG may be efficiently tethered to the Nylon 6 surface via DSC, having an enormous future potential for antifouling biomedical materials. The bacterial adhesion performances against S. aureus and P. aeruginosa were examined. In vitro cytocompatibility was successfully tested on pure, reduced, and PEG immobilized samples.
Mediatization of Beliefs: The Adventism from “Morning Star” to the Public Sphere
Authors: Bratosin Stefan
Published: September 2020

This article examines “the material becoming-forces of symbolic forms” mobilized by the Adventist beliefs in the public sphere of the United States of America during the 19th century. Particularly, the article focuses on the “transformation” of the prophetic letter’s secret of the Bible into “communicative action”, which is both civil and religious. The article aims to test the strengths and the weaknesses of Adventism’s symbolic function in the paradigmatic myth of the State, on the assumption that, in the creation of spiritual meaning in the present world, Adventism is an external referent to social transformation. Theoretical and exploratory in nature, this article also seeks to broaden the understanding of an atypical religion—“without particular religion”—through the old and the new media theory and research program of mediatization.
The Contribution of Church-Based Networks to Social Care in the Coronavirus Pandemic and Beyond: The Case of Pastoral da Pessoa Idosa in Brazil
Authors: Kevern Peter , Lopes Ruth , Barroso Áurea , Côrte Beltrina , Lucena Carolina
Published: September 2020

The Pastoral da Pessoa Idosa (PPI) is a national voluntary movement linked to the National Conference of Bishops of Brazil (CNBB), comprising approximately 2500 volunteers, who offer guidance and support for well-being to more than 170,000 older people throughout Brazil. This paper analyses the results of a data gathering exercise designed to gain an overview of the scope, support needs and international transferability of the project in ‘normal’ times and during the coronavirus pandemic. A telephone questionnaire comprising 21 questions was launched nationally among PPI volunteers over a single week in May 2020. The dataset (n = 3888) was subjected to exploratory statistical analysis and key findings collated around three guiding questions. The central findings were, first, that the composition of the body of volunteers is changing, requiring changes to training and support; secondly, that the model may be exportable to other middle-income countries in which the Catholic Church does not have the same dominance over the culture, as long as a national organising structure is in place; and finally that the speedy and flexible response of the PPI to the coronavirus pandemic suggests that this type of NGO will have a role in response to future national crises.