bluuebunny/crossref_metadata_2025 huggingface dataset:
Principal Component Analysis of Munich Functional Developmental Diagnosis
Authors: Pazera Grażyna , Młodawska Marta , Młodawski Jakub , Klimowska Kamila
Published: May 2021

Objectives: Munich Functional Developmental Diagnosis (MFDD) is a scale for assessing the psychomotor development of children in the first months or years of life. The tool is based on standardized tables of physical development and is used to detect developmental deficits. It consists of eight axes on which the following skills are assessed: crawling, sitting, walking, grasping, perception, speaking, speech understanding, social skills. Methods: The study included 110 children in the first year of life examined with the MFDD by the same physician. The score obtained on a given axis was coded as a negative value (defined in months) below the child’s age-specific developmental level. Next, we examined the dimensionality of the scale and the intercorrelation of its axes using polychoric correlation and principal component analysis. Results: Correlation matrix analysis showed high correlation of MFDD axes 1–4, and MFDD 6–8. The PCA identified three principal components consisting of children’s development in the areas of large and small motor skills (axis 1–4), perception (axis 5), active speech, passive speech and social skills (axis 6–8). The three dimensions obtained together account for 80.27% of the total variance. Conclusions: MFDD is a three-dimensional scale that includes motor development, perception, and social skills and speech. There is potential space for reduction in the number of variables in the scale.
Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation
Authors: Moraes Carolina , Zaverucha-do-Valle Camila , Fleurance Renaud , Sharshar Tarek , Bozza Fernando , d’Avila Joana
Published: May 2021

Frequently underestimated, encephalopathy or delirium are common neurological manifestations associated with sepsis. Brain dysfunction occurs in up to 80% of cases and is directly associated with increased mortality and long-term neurocognitive consequences. Although the central nervous system (CNS) has been classically viewed as an immune-privileged system, neuroinflammation is emerging as a central mechanism of brain dysfunction in sepsis. Microglial cells are major players in this setting. Here, we aimed to discuss the current knowledge on how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. This review focused on the molecular pathways of microglial activity in sepsis, its regulatory mechanisms, and their interaction with other CNS cells, especially with neuronal cells and circuits.
Recent Advances in Hepatitis B Treatment
Authors: Prifti Georgia-Myrto , Moianos Dimitrios , Giannakopoulou Erofili , Pardali Vasiliki , Tavis John , Zoidis Grigoris
Published: May 2021

Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.
Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance
Authors: Crișan Andrea Gabriela , Porfire Alina , Ambrus Rita , Katona Gábor , Rus Lucia Maria , Porav Alin Sebastian , Ilyés Kinga , Tomuță Ioan
Published: May 2021

Three-dimensional printing (3DP) by fused deposition modeling (FDM) has gained momentum as a promising pharmaceutical manufacturing method due to encouraging forward-looking perspectives in personalized medicine preparation. The current challenges the technology has for applicability in the fabrication of solid dosage forms include the limited range of suitable pharmaceutical grade thermoplastic materials. Hence, it is important to investigate the implications of variable properties of the polymeric carrier on the preparation steps and the final output, as versatile products could be obtained by using the same material. In this study, we highlighted the influence of polyvinyl alcohol (PVA) particle size on the residence time of the mixtures in the extruder during the drug-loaded filament preparation step and the consequent impact on drug release from the 3D printed dosage form. We enhanced filament printability by exploiting the plasticizing potential of the active pharmaceutical ingredient (API) and we explored a channeled tablet model as a design strategy for dissolution facilitating purposes. Our findings disclosed a new perspective regarding material considerations for the preparation of PVA-based solid dosage forms by coupling hot melt extrusion (HME) and FDM-3DP.
Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion
Authors: Martín-Escolano Rubén , Molina-Carreño Daniel , Plano Daniel , Espuelas Socorro , Rosales María J. , Moreno Esther , Aydillo Carlos , Sanmartín Carmen , Sánchez-Moreno Manuel , Marín Clotilde
Published: May 2021

Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.
Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates
Authors: Ali Tanveer , Basit Abdul , Karim Asad Mustafa , Lee Jung-Hun , Jeon Jeong-Ho , Rehman Shafiq ur , Lee Sang-Hee
Published: May 2021

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.
ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells
Authors: Danieau Geoffroy , Morice Sarah , Renault Sarah , Brion Régis , Biteau Kevin , Amiaud Jérôme , Cadé Marie , Heymann Dominique , Lézot Frédéric , Verrecchia Franck , Rédini Françoise , Brounais-Le Royer Bénédicte
Published: May 2021

High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.
Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties
Authors: Kovaleva Kseniya , Yarovaya Olga , Ponomarev Konstantin , Cheresiz Sergey , Azimirad Amirhossein , Chernyshova Irina , Zakharenko Alexandra , Konev Vasily , Khlebnikova Tatiana , Mozhaytsev Evgenii , Suslov Evgenii , Nilov Dmitry , Švedas Vytas , Pokrovsky Andrey , Lavrik Olga , Salakhutdinov Nariman
Published: May 2021

In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19–2.3 µM) and demonstrated low cytotoxicity in the T98G glioma cell line. The effect of the terpene fragment, the linker structure, and the adamantane residue on the biological properties of the new compounds was investigated. Based on molecular docking results, we suppose that adamantane derivatives of resin acids bind to the TDP1 covalent intermediate, forming a hydrogen bond with Ser463 and hydrophobic contacts with the Phe259 and Trp590 residues and the oligonucleotide fragment of the substrate.
Therapeutic Use of Valproic Acid and All-Trans Retinoic Acid in Acute Myeloid Leukemia—Literature Review and Discussion of Possible Use in Relapse after Allogeneic Stem Cell Transplantation
Authors: Bruserud Øystein , Tsykunova Galina , Hernandez-Valladares Maria , Reikvam Hakon , Tvedt Tor Henrik Anderson
Published: May 2021

Even though allogeneic stem cell transplantation is the most intensive treatment for acute myeloid leukemia (AML), chemo-resistant leukemia relapse is still one of the most common causes of death for these patients, as is transplant-related mortality, i.e., graft versus host disease, infections, and organ damage. These relapse patients are not always candidates for additional intensive therapy or re-transplantation, and many of them have decreased quality of life and shortened expected survival. The efficiency of azacitidine for treatment of posttransplant AML relapse has been documented in several clinical trials. Valproic acid is an antiepileptic fatty acid that exerts antileukemic activity through histone deacetylase inhibition. The combination of valproic acid and all-trans retinoic acid (ATRA) is well tolerated even by unfit or elderly AML patients, and low-toxicity chemotherapy (e.g., azacitidine) can be added to this combination. The triple combination of azacitidine, valproic acid, and ATRA may therefore represent a low-intensity and low-toxicity alternative for these patients. In the present review, we review and discuss the general experience with valproic acid/ATRA in AML therapy and we discuss its possible use in low-intensity/toxicity treatment of post-allotransplant AML relapse. Our discussion is further illustrated by four case reports where combined treatments with sequential azacitidine/hydroxyurea, valproic acid, and ATRA were used.
Microencapsulation of Bacteriophages Using Membrane Emulsification in Different pH-Triggered Controlled Release Formulations for Oral Administration
Authors: Richards Kerry , Malik Danish J.
Published: May 2021

An E.coli-specific phage was encapsulated in three different pH responsive polymer formulations using the process of membrane emulsification. Small 100 µm capsules were fabricated and shown to afford phages suitable acid protection upon exposure to pH 1.5. Selection of polymer formulations allowed controlled release of phages at pH 5.5, pH 6 and pH 7. Other aspects of phage encapsulation including factors affecting encapsulation yield, release kinetics, acid and storage stability were evaluated. The work presented here would be useful for future evaluation of new therapeutic strategies including microbiome editing approaches allowing pH-triggered release of phages and delivery of encapsulated cargo to different intestinal compartments. The size of the capsules were selected to permit ease of delivery using small bore oral gavage tubes typically used in pre-clinical studies for evaluation of drug substances using small animal vertebrate models such as in mice and rats.
Signal Detection of Adverse Drug Reactions of Cephalosporins Using Data from a National Pharmacovigilance Database
Authors: Choi Jung-Yoon , Choi Jae-Hee , Kim Myeong-Gyu , Rhie Sandy-Jeong
Published: May 2021

This case-non-case study aims to detect signals not currently listed on cephalosporin drug labels. From 2009 to 2018, adverse event (AE) reports concerning antibacterial drugs (anatomical therapeutic chemical (ATC) code J01) in the Korea Adverse Events Reporting System (KAERS) database were examined. For signal detection, three indices of disproportionality, proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC), were calculated. The list of signals was compared with ADRs on the drug labels from the United States, United Kingdom, Japan, and South Korea. A total of 163,800 cephalosporin–AE combinations and 72,265 all other J01–AE combinations were analyzed. This study detected 472 signals and 114 new signals that are not included on the drug labels. Cefatrizine–corneal edema (PRR, 440.64; ROR, 481.67; IC, 3.84) and cefatrizine–corneal ulceration (PRR, 346.22; ROR, 399.70; IC, 4.40) had the highest PRR, ROR, and IC among all signals. Additionally, six serious AEs that were not listed on drug labels such as cefaclor-induced stupor (ten cases) and cefaclor-induced respiratory depression (four cases) were found. Detecting signals using a national pharmacovigilance database is useful for identifying unknown ADRs. This study identified signals of cephalosporins that warrant further investigation.
Dicopper(II)-EDTA Chelate as a Bicephalic Receptor Model for a Synthetic Adenine Nucleoside
Authors: García-Rubiño María Eugenia , Matilla-Hernández Antonio , Frontera Antonio , Lezama Luis , Niclós-Gutiérrez Juan , Choquesillo-Lazarte Duane
Published: May 2021

In the extensive field of metal ions, their interactions with nucleic acids, and their constituents, the main aim of this work is to develop a metal chelate suitable to recognize two molecules of an adenine nucleoside. For this purpose, the dinuclear chelate Cu2 (µ-EDTA) (ethylenediaminetetraacetate(4-) ion (EDTA)) is chosen as a bicephalic receptor model for N9-(2-hydroxyethyl)adenine (9heade). A one-pot synthesis is reported to obtain the compound [Cu2(µ2-EDTA)(9heade)2(H2O)4]·3H2O, which has been characterized by single-crystal X-ray diffraction and various spectral, thermal, and magnetic methods. The complex unit is a centro-symmetric molecule, where each Cu (II) center is chelated by a half-EDTA, and is further surrounded by an N7-dentate 9heade nucleoside and two non-equivalent trans-O-aqua molecules. The metal chelate-nucleoside molecular recognition is referred to as an efficient cooperation between the Cu-N7(9heade) coordination bond and a (9heade)N6-H···O(carboxyl, EDTA) interligand interaction. Theoretical calculations are also made to account for the relevance of this interaction. The extreme weakness with which each water molecule binds to the metal center disturbs the thermal stability and the infrared (FT-IR) and electron spin resonance (ESR) spectra of the compound.
Antibody–Drug Conjugate to Treat Meningiomas
Authors: Chen Kai , Si Yingnan , Ou Jianfa , Guan Jia-Shiung , Kim Seulhee , Ernst Patrick , Zhang Ya , Zhou Lufang , Han Xiaosi , Liu Xiaoguang (Margaret)
Published: May 2021

Meningiomas are primary tumors of the central nervous system with high recurrence. It has been reported that somatostatin receptor 2 (SSTR2) is highly expressed in most meningiomas, but there is no effective targeted therapy approved to control meningiomas. This study aimed to develop and evaluate an anti-SSTR2 antibody–drug conjugate (ADC) to target and treat meningiomas. The meningioma targeting, circulation stability, toxicity, and anti-tumor efficacy of SSTR2 ADC were evaluated using cell lines and/or an intracranial xenograft mouse model. The flow cytometry analysis showed that the anti-SSTR2 mAb had a high binding rate of >98% to meningioma CH157-MN cells but a low binding rate of <5% to the normal arachnoidal AC07 cells. The In Vivo Imaging System (IVIS) imaging demonstrated that the Cy5.5-labeled ADC targeted and accumulated in meningioma xenograft but not in normal organs. The pharmacokinetics study and histological analysis confirmed the stability and minimal toxicity. In vitro anti-cancer cytotoxicity indicated a high potency of ADC with an IC50 value of <10 nM. In vivo anti-tumor efficacy showed that the anti-SSTR2 ADC with doses of 8 and 16 mg/kg body weight effectively inhibited tumor growth. This study demonstrated that the anti-SSTR2 ADC can target meningioma and reduce the tumor growth.
Flavonoids from the Genus Euphorbia: Isolation, Structure, Pharmacological Activities and Structure–Activity Relationships
Authors: Magozwi Douglas Kemboi , Dinala Mmabatho , Mokwana Nthabiseng , Siwe-Noundou Xavier , Krause Rui W. M. , Sonopo Molahlehi , McGaw Lyndy J. , Augustyn Wilma A. , Tembu Vuyelwa Jacqueline
Published: May 2021

Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship of Euphorbia flavonoids for the period covering 2000–2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure–activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents.
Resistivity Technique for the Evaluation of the Integrity of Buccal and Esophageal Epithelium Mucosa for In Vitro Permeation Studies: Swine Buccal and Esophageal Mucosa Barrier Models
Authors: de Araújo Jaiza Samara Macena , Volpato Maria Cristina , Muniz Bruno Vilela , Xavier Gabriela Gama Augusto , Martinelli Claudia Cristina Maia , Lopez Renata Fonseca Vianna , Groppo Francisco Carlos , Franz-Montan Michelle
Published: May 2021

Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh and frozen swine buccal and esophageal epithelia were mounted in Franz diffusion cells and were then submitted to ER measurement. Permeation assays were performed using lidocaine hydrochloride as a hydrophilic drug model. ER was shown to be a reliable method for evaluating esophageal and buccal epithelia. The esophageal epithelium presented higher permeability compared to the buccal epithelium. For both epithelia, freezing and storage led to decreased electrical resistivity and increased permeability. We conclude that ER may be safely used to confirm tissue integrity when it is equal to or above 3 kΩ for fresh esophageal mucosa, but not for buccal epithelium mucosa. However, the use of esophageal epithelium in in vitro transmucosal studies could overestimate the absorption of hydrophilic drugs. In addition, fresh samples are recommended for these experiments, especially when hydrophilic drugs are involved.
Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines
Authors: Abbasi Saed , Uchida Satoshi
Published: May 2021

Subunit vaccines based on antigen-encoding nucleic acids have shown great promise for antigen-specific immunization against cancer and infectious diseases. Vaccines require immunostimulatory adjuvants to activate the innate immune system and trigger specific adaptive immune responses. However, the incorporation of immunoadjuvants into nonviral nucleic acid delivery systems often results in fairly complex structures that are difficult to mass-produce and characterize. In recent years, minimalist approaches have emerged to reduce the number of components used in vaccines. In these approaches, delivery materials, such as lipids and polymers, and/or pDNA/mRNA are designed to simultaneously possess several functionalities of immunostimulatory adjuvants. Such multifunctional immunoadjuvants encode antigens, encapsulate nucleic acids, and control their pharmacokinetic or cellular fate. Herein, we review a diverse class of multifunctional immunoadjuvants in nucleic acid subunit vaccines and provide a detailed description of their mechanisms of adjuvanticity and induction of specific immune responses.
Parametric Study of Residence Time Distributions and Granulation Kinetics as a Basis for Process Modeling of Twin-Screw Wet Granulation
Authors: Plath Timo , Korte Carolin , Sivanesapillai Rakulan , Weinhart Thomas
Published: May 2021

Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus have limited universal validity. In this study, an experimental design with a repetitive screw setup was conducted to measure the effect of specific feed load (SFL), liquid-to-solid ratio (L/S), and inclusion of a distributive feed screw on particle size distribution (PSD) and shape as well as residence time distribution of a hydrophilic lactose/microcrystalline cellulose based formulation. An intermediate sampling point was obtained by changing inlet ports along the screw axis. Camera-based particle size analysis (QICPIC) indicated no significant change of PSD between the first and second kneading section, except for low L/S and low SFL where fines increase. Mean residence time was approximated as a bilinear fit of L/S and SFL. Moreover, large mass flow pulsations were observed by continuous camera measurements of residence time distribution and correlated to hold-up of the twin-screw granulator. These findings indicate fast granulation kinetics and process instabilities for high mean residence times, questioning current standards of two kneading compartments for wet granulation. The present study further underlines the necessity of developing a multiscale simulation approach including particle dynamics in the future.
Design and Optimization of Orally Administered Luteolin Nanoethosomes to Enhance Its Anti-Tumor Activity against Hepatocellular Carcinoma
Authors: Elsayed Mahmoud , Okda Tarek , Atwa Gamal , Omran Gamal , Abd Elbaky Atef , Ramadan Abd
Published: May 2021

Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.
Cross-Sectional Survey among General Population Regarding Knowledge and Attitude toward Antibiotic Usage in Western Saudi Arabia
Authors: Zaidi Syed Faisal , Baroom Muhannad Wael , Ibrahim Hanbashi Adil , Abdulaziz Alkhaibari Abdulrahman , Omar Yahya Ahmed , Alsalmi Muath , Alotaibi Rakan , Nagro Abdulaziz , Anwar Khan Muhammad , Alshanberi Asim Muhammed
Published: May 2021

Background: Antibiotic resistance is a threatening issue to human wellbeing and an obstacle in the treatment process of many life-threating illnesses. This study aims to assess the knowledge and attitudes toward antibiotic usage among the general population in Jeddah, Saudi Arabia. Methods: A self-administered cross-sectional survey of 460 participants was distributed among the general population in Jeddah in the form of a validated questionnaire. Sample size was calculated to be 460 adults of either gender. Descriptive and inferential statistical analyses were performed using the Statistical Package for Social Sciences. Results: the age of more than half of participants (55.6%) was 18–30 years old, followed by the age group 31–40 years old (26.6%), with the smallest age group >60 years old (1.9%). More than two thirds of participants were male (69.5%), while 131 were female, accounting for 30.5%. Almost one third of participants had poor knowledge about antibiotics (30.5%), 51.0% had used antibiotics without any prescriptions, 54.6% of participants thought antibiotics could be used to treat viral infections, and 55.1% thought it was acceptable to stop taking antibiotics if symptoms start to improve. In addition, 49% believed that taking antibiotics would help them get better more rapidly when suffering from the common cold. Some personal characteristics were significantly associated with the public’s knowledge (e.g., age, education, and monthly income) and their attitudes (e.g., monthly income). Conclusion: Findings revealed a low level of knowledge on the use of antibiotics among the general public in Jeddah. This study signifies the need for improvement in the public’s knowledge and enhancement of their attitudes toward proper utilization of antibiotics.
Theoretical Study of Tunable Optical Resonators in Periodic and Quasiperiodic One-Dimensional Photonic Structures Incorporating a Nematic Liquid Crystal
Authors: Trabelsi Youssef. , Belhadj Walid. , Ben Ali Naim. , Aly Arafa H.
Published: May 2021

In this work, the transfer matrix method (TMM) is employed to investigate the optical properties of one-dimensional periodic and quasiperiodic photonic crystals containing nematic liquid crystal (NLC) layers. This structure is expressed as (ABC)J(CBA)J and made of alternated layers of isotropic dielectrics SiO2 (A), BGO (B) and nematic liquid crystal (C). The simulation study shows that the proposed ternary configuration exhibits tunable defect mode within the photonic band gap (PBG) that can be manipulated by adjusting the thicknesses of NLC layers in order of the periodic lattice. In addition, the optimized structure permits for strong confinement light giving rise to an optical microcavity. The application of an applied voltage into NLC layers enables improving the sensitivity by guiding the local defect mode. It has been also shown that by applying quasiperiodic inflation according to Rudin Shapiro Sequence (RSS) scheme to main periodic structure, several tunable resonant modes appear within the PBG. The presence of such sharp resonant peaks reflects that the quasiperiodic NLC-based structure behaves like multiple microcavites with strong light-matter coupling.
Label-Free Observation of Micrometric Inhomogeneity of Human Breast Cancer Cell Density Using Terahertz Near-Field Microscopy
Authors: Okada Kosuke , Cassar Quentin , Murakami Hironaru , MacGrogan Gaëtan , Guillet Jean-Paul , Mounaix Patrick , Tonouchi Masayoshi , Serita Kazunori
Published: May 2021

Terahertz-light imaging is attracting great attention as a new approach in non-invasive/non-staining biopsy of cancerous tissues. Positively, terahertz light has been shown to be sensitive to the cell density, the hydration content, and the chemical composition of biological samples. However, the spatial resolution of terahertz imaging is typically limited to several millimeters, making it difficult to apply the technology to image biological tissues which have sub-terahertz-wavelength-scale inhomogeneity. For overcoming the resolution, we have recently developed a terahertz near-field microscope with a spatial resolution of 10 µm, named scanning point terahertz source (SPoTS) microscope. In contrast to conventional far-field terahertz techniques, this microscope features the near-field interactions between samples and point terahertz sources on a sub-terahertz-wavelength scale. Herein, to evaluate the usefulness of terahertz imaging in cancer tissue biopsy in greater detail, we performed terahertz near-field imaging of a paraffin-embedded human-breast-cancer section having sub-terahertz-wavelength-scale inhomogeneity of the cancer cell density using the SPoTS microscope. The observed terahertz images successfully visualized local (~250 µm) inhomogeneities of the cell density in breast invasive ductal carcinoma. These results may bypass the terahertz limitation in terms of spatial resolution and may further motivate the application of terahertz light to cancer tissue biopsy.
Photorespiration: The Futile Cycle?
Authors: Shi Xiaoxiao , Bloom Arnold
Published: May 2021

Photorespiration, or C2 photosynthesis, is generally considered a futile cycle that potentially decreases photosynthetic carbon fixation by more than 25%. Nonetheless, many essential processes, such as nitrogen assimilation, C1 metabolism, and sulfur assimilation, depend on photorespiration. Most studies of photosynthetic and photorespiratory reactions are conducted with magnesium as the sole metal cofactor despite many of the enzymes involved in these reactions readily associating with manganese. Indeed, when manganese is present, the energy efficiency of these reactions may improve. This review summarizes some commonly used methods to quantify photorespiration, outlines the influence of metal cofactors on photorespiratory enzymes, and discusses why photorespiration may not be as wasteful as previously believed.
Role of Two Plant Growth-Promoting Bacteria in Remediating Cadmium-Contaminated Soil Combined with Miscanthus floridulus (Lab.)
Authors: Liu Shuming , Liu Hongmei , Chen Rui , Ma Yong , Yang Bo , Chen Zhiyong , Liang Yunshan , Fang Jun , Xiao Yunhua
Published: May 2021

Miscanthus spp. are energy plants and excellent candidates for phytoremediation approaches of metal(loid)s-contaminated soils, especially when combined with plant growth-promoting bacteria. Forty-one bacterial strains were isolated from the rhizosphere soils and roots tissue of five dominant plants (Artemisia argyi Levl., Gladiolus gandavensis Vaniot Houtt, Boehmeria nivea L., Veronica didyma Tenore, and Miscanthus floridulus Lab.) colonizing a cadmium (Cd)-contaminated mining area (Huayuan, Hunan, China). We subsequently tested their plant growth-promoting (PGP) traits (e.g., production of indole-3-acetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate deaminase) and Cd tolerance. Among bacteria, two strains, Klebsiella michiganensis TS8 and Lelliottia jeotgali MR2, presented higher Cd tolerance and showed the best results regarding in vitro growth-promoting traits. In the subsequent pot experiments using soil spiked with 10 mg Cd·kg−1, we investigated the effects of TS8 and MR2 strains on soil Cd phytoremediation when combined with M. floridulus (Lab.). After sixty days of planting M. floridulus (Lab.), we found that TS8 increased plant height by 39.9%, dry weight of leaves by 99.1%, and the total Cd in the rhizosphere soil was reduced by 49.2%. Although MR2 had no significant effects on the efficiency of phytoremediation, it significantly enhanced the Cd translocation from the root to the aboveground tissues (translocation factor > 1). The combination of K. michiganensis TS8 and M. floridulus (Lab.) may be an effective method to remediate Cd-contaminated soils, while the inoculation of L. jeotgali MR2 may be used to enhance the phytoextraction potential of M. floridulus.
Sequential Antioxidants Foliar Application Can Alleviate Negative Consequences of Salinity Stress in Vicia faba L.
Authors: Semida Wael M. , Abd El-Mageed Taia A. , Abdalla Reham M. , Hemida Khaulood A. , Howladar Saad. M. , Leilah Ahmed A. A. , Rady Mohamed O. A.
Published: May 2021

Salinity is one of the most limiting abiotic stresses in agricultural productivity. Exogenously applied antioxidants successfully enabled salt-stressed plants to cope with stress. Two-season field experiments were conducted consecutively in 2016/17 and 2017/18 to study the effects of foliar applications of singular (ascorbate, AsA; proline, Pro; and glutathione, GSH) or sequential (AsA-Pro-GSH and GSH-Pro-AsA) antioxidants on growth, yield, physio-biochemical attributes, and enzymatic and non-enzymatic antioxidative defense system of Vicia faba L. (CV. Sakha-1) plants grown under saline soil conditions (EC = 4.53 dS m−1). Under soil salinity conditions, AsA, Pro, or GSH-Pro-ASA improved growth and productivity, photosynthesis efficiency, stomatal conductance (gs), plant water status, as well as enzymatic and non-enzymatic antioxidants. However, sequential AsA-Pro-GSH foliar application followed by singular GSH significantly exceeded all other treatments (i.e., AsA, Pro, and GSH-Pro-AsA), improving growth characteristics (shoot length, shoot fresh and dry weights, and leaves area), photosynthesis efficiency, stomatal conductance, plant water status, and yield and its components (green pods weight/plant−1, green pods yield/hectare−1, and seed yield/hectare−1), as well as enzymatic (ascorbate peroxidase, catalase, superoxide dismutase, and glutathione reductase) and non-enzymatic (AsA, GSH, Pro, phenolic aglycone, phenolic glycosides) antioxidants compared to control. Overall, our results clearly demonstrate that sequential AsA-Pro-GSH foliar application has a positive effect on salt-stressed Vicia faba plants.
Evaluation of the Conditions for the Cultivation of Callus Cultures of Hyssopus officinalis Regarding the Yield of Polyphenolic Compounds
Authors: Babich Olga , Sukhikh Stanislav , Pungin Artem , Astahova Lidiya , Chupakhin Evgeny , Belova Daria , Prosekov Alexander , Ivanova Svetlana
Published: May 2021

The cultivation of plants in the form of callus cultures constitutes a renewable source of secondary plant metabolites. The conditions for the cultivation of callus cultures affect the yield of target compounds. Callus cultures of Hyssopus officinalis were chosen for study. Nutrient media of various compositions were used for Hyssopus officinalis callus culture. For each culture, data on the quantitative contents of saponins, flavonoids and polyphenolic compounds, as well as antioxidant activity, were obtained. It was found that Murashige and Skoog medium supplemented with 1-naphthylacetic acid and kinetin led to the highest yield of secondary metabolites.
Stability of Film-Forming Dispersions: Affects the Morphology and Optical Properties of Polymeric Films
Authors: De Paola Maria Gabriela , Paletta Rosy , Lopresto Catia Giovanna , Lio Giuseppe Emanuele , De Luca Antonio , Chakraborty Sudip , Calabrò Vincenza
Published: May 2021

Starch-based films are promising alternatives to synthetic films in food packaging. They were widely studied in terms of mechanical and optical properties. In food packaging, optical properties are of great interest because ultra violet (UV-light) protection is strictly required. Nevertheless, the characterization of film-forming dispersions was poorly addressed, especially regarding its correlation with the film produced. In this work, we characterized film-forming dispersions at different compositions of starch and carboxymethyl cellulose (CMC) by Turbiscan. This instrument is based on multiple light scattering and gives significant information about the miscibility of polymers in the dispersed phase. Indeed, it identifies the phenomena of destabilization and phase separation before their visibility to the unaided eye. This work aimed to study whether the homogeneous/inhomogeneous morphology of films could be forecast by the analysis of profiles obtained in the dispersed phase. The films produced were investigated by optical microscopy and absorbance analysis. As the CMC fraction increased, Turbiscan showed reduced phase separation. This implies better miscibility of mixture components and higher gelification degree. The related film was more homogeneous and presented higher UV absorbance. Consequently, film-forming dispersions and optical properties of films are strictly correlated and Turbiscan-based analysis is very useful to investigate the dispersion stability and predict the film quality.
Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel
Authors: Petrova Svetlana Lukáš , Jäger Eliézer , Jäger Alessandro , Höcherl Anita , Konefał Rafał , Zhigunov Alexander , Pavlova Ewa , Janoušková Olga , Hrubý Martin
Published: May 2021

Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-b-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-b-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy.
Application of Polymer Drugs with Cerium Dioxide Nanomolecules and Mesenchymal Stem Cells for the Treatment of Skin Wounds in Aged Rats
Authors: Silina Ekaterina Vladimirovna , Stupin Victor Aleksandrovich , Suzdaltseva Yulia Gennadievna , Aliev Salekh Rovshanovich , Abramov Igor Sergeevich , Khokhlov Nikolay Valerievich
Published: May 2021

The urgency of the problem of wound healing is not in doubt, given the global trend of an increase in the number of operations and injuries with skin damage, as well as the lack of universal means of treating wounds. Study Objective: To compare the effectiveness of the developed drugs, smart polymeric nano-drug with cerium oxide nanoparticles (SPN), and smart polymeric nano-drug in combination with mesenchymal stem cells (SPN + SC) on the healing process of skin wounds. Material and methods. An experimental study was carried out using Wistar rats of post-reproductive age, which had dermis and epidermis removed on their backs. There were four groups of wounds in total: control, treatment with mesenchymal stem cells (SC), SPN, and SPN + SC. Results. A positive therapeutic effect of polymeric drugs on the dynamics of wound area reduction was established, which was most typical for wounds of the SPN group and, particularly, the SPN + SC group. On the third day, an anti-inflammatory effect was revealed in the SC and the SPN + SC groups in particular, which was expressed in a reduced leukocyte infiltration and an increase in the level of microcirculation during this period. The fastest transition from the phase of exudation to proliferation was recorded in the SPN and SPN + SC groups. Histologically, these groups showed faster regeneration, including the epithelialization of wounds. Conclusion. The results obtained in the course of the study open up possibilities for the development of fundamentally new, highly effective wound healing agents.
In-Situ Visualization of the Cell Formation Process of Foamed Polypropylene under Different Foaming Environments
Authors: Deng Rong , Jiang Tuanhui , Zhang Chun , Zeng Xiangbu , Liu Bujin , Yang Jingkui , Li Shengnan , Gu Jun , Gong Wei , He Li
Published: May 2021

In this paper, the dynamic foaming process of micro-foaming polypropylene (PP) in different foaming environments in real time was obtained via a visualization device. The relationship curve between cell number (n) and foaming time (t) was plotted, and then the nucleation kinetics of foam cells was analyzed. Results showed that the formation rate of cells changed obviously with the variation of melt temperature and the content of the foaming agent. The n-t curves presented a typical “S” shape, which indicated that the appearance of the cell number increased slowly in the initial foaming period, then increased rapidly in a short time, and finally maintained a certain value. When a certain pressure was applied to the PP melt, the external force had a great influence on the n-t curve. With the increasing external force, the rate of cell formation increased rapidly, and the shape of the n-t curve changed from “S” to “semi-S” without an obvious slow increase. The investigation of the n-t relationship in the PP dynamic foaming process under different foaming environments could provide effective bases for improving the foaming quality of injection molding foaming materials.
The Structure, Morphology, and Complex Permittivity of Epoxy Nanodielectrics with In Situ Synthesized Surface-Functionalized SiO2
Authors: Adnan Mohammed Mostafa , Nylund Inger-Emma , Jaworski Aleksander , Hvidsten Sverre , Ese Marit-Helen Glomm , Glaum Julia , Einarsrud Mari-Ann
Published: May 2021

Epoxy nanocomposites have demonstrated promising properties for high-voltage insulation applications. An in situ approach to the synthesis of epoxy-SiO2 nanocomposites was employed, where surface-functionalized SiO2 (up to 5 wt.%) is synthesized directly in the epoxy. The dispersion of SiO2 was found to be affected by both the pH and the coupling agent used in the synthesis. Hierarchical clusters of SiO2 (10–60 nm) formed with free-space lengths of 53–105 nm (increasing with pH or SiO2 content), exhibiting both mass and surface-fractal structures. Reducing the amount of coupling agent resulted in an increase in the cluster size (~110 nm) and the free-space length (205 nm). At room temperature, nanocomposites prepared at pH 7 exhibited up to a 4% increase in the real relative permittivity with increasing SiO2 content, whereas those prepared at pH 11 showed up to a 5% decrease with increasing SiO2 content. Above the glass transition, all the materials exhibited low-frequency dispersion effect resulting in electrode polarization, which was amplified in the nanocomposites. Improvements in the dielectric properties were found to be not only dependent on the state of dispersion, but also the structure and morphology of the inorganic nanoparticles.