bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung-Centric Inflammation of COVID-19: Potential Modulation by Vitamin D
Authors: Fakhoury Hana. M. A. , Kvietys Peter R. , Shakir Ismail , Shams Hashim , Grant William B. , Alkattan Khaled
Published: June 2021

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed.
Oral Hyaluronan Relieves Wrinkles and Improves Dry Skin: A 12-Week Double-Blinded, Placebo-Controlled Study
Authors: Hsu Tzu-Fang , Su Zi-Rong , Hsieh Yao-Hao , Wang Ming-Fu , Oe Mariko , Matsuoka Ryosuke , Masuda Yasunobu
Published: June 2021

Hyaluronan (HA) is present in all connective tissues and organs, including the skin and joint fluid. However, few clinical trials have comprehensively evaluated the impacts of oral HA on skin conditions, including wrinkles and moisturization. In this study, we conducted a placebo-controlled, randomized, double-blind trial of daily HA (120 mg) intake for 12 weeks in 40 healthy Asian men and women (aged 35–64 years). Skin condition was determined by the evaluation of wrinkles, stratum corneum water content, the amount of transepidermal water loss, elasticity, and through image analysis. After 12 weeks, skin condition was significantly improved in terms of wrinkle assessment, stratum corneum water content, transepidermal water loss, and elasticity in the HA group compared to the placebo group. Regarding the percentage change from baseline, wrinkle assessment, stratum corneum water content, and skin elasticity were significantly improved in the HA group versus the placebo group after 8 and 12 weeks of ingestion. The present findings indicate that oral ingestion of HA may suppress wrinkles and improve skin condition.
Maternal Iron Status in Pregnancy and Child Health Outcomes after Birth: A Systematic Review and Meta-Analysis
Authors: Quezada-Pinedo Hugo G. , Cassel Florian , Duijts Liesbeth , Muckenthaler Martina U. , Gassmann Max , Jaddoe Vincent W. V. , Reiss Irwin K. M. , Vermeulen Marijn J.
Published: June 2021

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.
Effectiveness and Safety of a Single-Dose Ivermectin Treatment for Uncomplicated Strongyloidiasis in Immunosuppressed Patients (ImmunoStrong Study): The Study Protocol
Authors: Salvador Fernando , Lucas-Dato Ana , Roure Silvia , Arsuaga Marta , Pérez-Jacoiste Asunción , García-Rodríguez Magdalena , Pérez-Molina José A. , Buonfrate Dora , Saugar José María , Molina Israel
Published: June 2021

Strongyloidiasis affects an estimated 600 million people worldwide, especially in tropical and subtropical areas. Single-dose ivermectin treatment has shown to be effective among immunocompetent patients with uncomplicated strongyloidiasis. Here, we present the protocol of the ImmunoStrong study, a prospective observational study aiming to evaluate the effectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients. The secondary objectives are to assess accuracy of molecular techniques for the follow-up of these patients and to determine the population pharmacokinetics of ivermectin. The information retrieved by this study will cover relevant information gaps in the strongyloidiasis management among immunosuppressed patients.
Therapeutic Drug Monitoring of Busulfan in Patients Undergoing Hematopoietic Cell Transplantation: A Pilot Single-Center Study in Taiwan
Authors: Chen Rong-Long , Fang Li-Hua , Yang Xin-Yi , El Amrani Mohsin , Uijtendaal Esther Veronique , Chen Yen-Fu , Ku Wei-Chi
Published: June 2021

Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population; Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated; The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of <15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient; This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.
High-Throughput Phenotypic Assay to Screen for Anthelmintic Activity on Haemonchus contortus
Authors: Taki Aya C. , Byrne Joseph J. , Wang Tao , Sleebs Brad E. , Nguyen Nghi , Hall Ross S. , Korhonen Pasi K. , Chang Bill C.H. , Jackson Paul , Jabbar Abdul , Gasser Robin B.
Published: June 2021

Parasitic worms cause very significant diseases in animals and humans worldwide, and their control is critical to enhance health, well-being and productivity. Due to widespread drug resistance in many parasitic worms of animals globally, there is a major, continuing demand for the discovery and development of anthelmintic drugs for use to control these worms. Here, we established a practical, cost-effective and semi-automated high throughput screening (HTS) assay, which relies on the measurement of motility of larvae of the barber’s pole worm (Haemonchus contortus) using infrared light-interference. Using this assay, we screened 80,500 small molecules and achieved a hit rate of 0.05%. We identified three small molecules that reproducibly inhibited larval motility and/or development (IC50 values of ~4 to 41 µM). Future work will critically assess the potential of selected hits as candidates for subsequent optimisation or repurposing against parasitic nematodes. This HTS assay has a major advantage over most previous assays in that it achieves a ≥ 10-times higher throughput (i.e., 10,000 compounds per week), and is thus suited to the screening of libraries of tens of thousands to hundreds of thousands of compounds for subsequent hit-to-lead optimisation or effective repurposing and development. The current assay should be adaptable to many socioeconomically important parasitic nematodes, including those that cause neglected tropical diseases (NTDs). This aspect is of relevance, given the goals of the World Health Organization (WHO) Roadmap for NTDs 2021–2030, to develop more effective drugs and drug combinations to improve patient outcomes and circumvent the ineffectiveness of some current anthelmintic drugs and possible drug resistance.
CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
Authors: Ferrero Maximiliano Ruben , Garcia Cristiana Couto , Dutra de Almeida Marcella , Torres Braz da Silva Jullian , Bianchi Reis Insuela Daniella , Teixeira Ferreira Tatiana Paula , de Sá Coutinho Diego , Trindade de Azevedo Carolina , Machado Rodrigues e Silva Patrícia , Martins Marco Aurélio
Published: June 2021

Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.
Dysregulation of Blood-Brain Barrier and Exacerbated Inflammatory Response in Cx47-Deficient Mice after Induction of EAE
Authors: Stavropoulos Filippos , Georgiou Elena , Sargiannidou Irene , Kleopa Kleopas A.
Published: June 2021

Induction of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), in connexin 32 (Cx32) or Cx47 knockout (KO) mice with deficiency in oligodendrocyte gap junctions (GJs) results in a more severe disease course. In particular, Cx47 KO EAE mice experience an earlier EAE onset and more pronounced disease severity, accompanied by dysregulated pro-inflammatory responses preceding the disease manifestations. In this study, analysis of relevant pro-inflammatory cytokines in wild type EAE, Cx32 KO EAE, and Cx47 KO EAE mice revealed altered expression of Vcam-1 preceding EAE [7 days post injection (dpi)], of Ccl2 at the onset of EAE (12 dpi), and of Gm-csf at the peak of EAE (24 dpi) in Cx47 KO EAE mice. Moreover, Cx47 KO EAE mice exhibited more severe blood-spinal cord barrier (BSCB) disruption, enhanced astrogliosis with defects in tight junction formation at the glia limitans, and increased T-cell infiltration prior to disease onset. Thus, Cx47 deficiency appears to cause dysregulation of the inflammatory profile and BSCB integrity, promoting early astrocyte responses in Cx47 KO EAE mice that lead to a more severe EAE outcome. Further investigation into the role of oligodendrocytic Cx47 in EAE and multiple sclerosis pathology is warranted.
Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces
Authors: Moghadaszadeh Masoud , Khayyati Mehdi , Spotin Adel , Norouzi Roghayeh , Pagheh Abdol Sattar , Oliveira Sonia M. R. , Pereira Maria de Lourdes , Ahmadpour Ehsan
Published: June 2021

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 μg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 μg/mL and 400 μg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.
Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells
Authors: Corvaglia Valentina , Ait Mohamed Amar Imène , Garambois Véronique , Letast Stéphanie , Garcin Aurélie , Gongora Céline , Del Rio Maguy , Denevault-Sabourin Caroline , Joubert Nicolas , Huc Ivan , Pourquier Philippe
Published: June 2021

Inhibition of protein–DNA interactions represents an attractive strategy to modulate essential cellular functions. We reported the synthesis of unique oligoamide-based foldamers that adopt single helical conformations and mimic the negatively charged phosphate moieties of B-DNA. These mimics alter the activity of DNA interacting enzymes used as targets for cancer treatment, such as DNA topoisomerase I, and they are cytotoxic only in the presence of a transfection agent. The aim of our study was to improve internalization and selective delivery of these highly charged molecules to cancer cells. For this purpose, we synthesized an antibody-drug conjugate (ADC) using a DNA mimic as a payload to specifically target cancer cells overexpressing HER2. We report the bioconjugation of a 16-mer DNA mimic with trastuzumab and its functional validation in breast and ovarian cancer cells expressing various levels of HER2. Binding of the ADC to HER2 increased with the expression of the receptor. The ADC was internalized into cells and was more efficient than trastuzumab at inhibiting their growth in vitro. These results provide proof of concept that it is possible to site-specifically graft high molecular weight payloads such as DNA mimics onto monoclonal antibodies to improve their selective internalization and delivery in cancer cells.
Zebrafish as a Model for Anticancer Nanomedicine Studies
Authors: Al-Thani Hissa F. , Shurbaji Samar , Yalcin Huseyin C.
Published: June 2021

Nanomedicine is a new approach to fight against cancer by the development of anticancer nanoparticles (NPs) that are of high sensitivity, specificity, and targeting ability to detect cancer cells, such as the ability of Silica NPs in targeting epithelial cancer cells. However, these anticancer NPs require preclinical testing, and zebrafish is a useful animal model for preclinical studies of anticancer NPs. This model affords a large sample size, optical imaging, and easy genetic manipulation that aid in nanomedicine studies. This review summarizes the numerous advantages of the zebrafish animal model for such investigation, various techniques for inducing cancer in zebrafish, and discusses the methods to assess cancer development in the model and to test for the toxicity of the anticancer drugs and NPs. In addition, it summarizes the recent studies that used zebrafish as a model to test the efficacy of several different anticancer NPs in treating cancer.
Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds
Authors: Alven Sibusiso , Khwaza Vuyolwethu , Oyedeji Opeoluwa O. , Aderibigbe Blessing A.
Published: June 2021

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.
Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells
Authors: Supruniuk Katarzyna , Czarnomysy Robert , Muszyńska Anna , Radziejewska Iwona
Published: June 2021

MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 μM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 μg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3, as well as pro- and cleaved caspase-3 protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to Bax protein and Bid expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards Akt and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy.
Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery
Authors: Cirri Marzia , Maestrelli Francesca , Nerli Giulia , Mennini Natascia , D’Ambrosio Mario , Luceri Cristina , Mura Paola Angela
Published: June 2021

A thermosensitive, mucoadhesive in-situ gel for clonazepam (CLZ) intranasal delivery was developed, which aimed to achieve prolonged in-situ residence and controlled drug release, overcoming problems associated with its oral or parenteral administration. Poloxamer was selected as a thermosensitive polymer and chitosan glutamate and sodium hyaluronate as mucoadhesive and permeation enhancer. Moreover, randomly methylated β-Cyclodextrin (RAMEB) was used to improve the low drug solubility. A screening DoE was applied for a systematic examination of the effect of varying the formulation components proportions on gelation temperature, gelation time and pH. Drug-loaded gels at different clonazepam-RAMEB concentrations were then prepared and characterized for gelation temperature, gelation time, gel strength, mucoadhesive strength, mucoadhesion time, and drug release properties. All formulations showed suitable gelation temperature (29–30.5 °C) and time (50–65 s), but the one with the highest drug-RAMEB concentration showed the best mucoadhesive strength, longest mucoadhesion time (6 h), and greatest release rate. Therefore, it was selected for cytotoxicity and permeation studies through Caco-2 cells, compared with an analogous formulation without RAMEB and a drug solution. Both gels were significantly more effective than the solution. However, RAMEB was essential not only to promote drug release, but also to reduce drug cytotoxicity and further improve its permeability.
Co-Encapsulation of Fisetin and Cisplatin into Liposomes for Glioma Therapy: From Formulation to Cell Evaluation
Authors: Renault-Mahieux Morgane , Vieillard Victoire , Seguin Johanne , Espeau Philippe , Le Dang Tri , Lai-Kuen René , Mignet Nathalie , Paul Muriel , Andrieux Karine
Published: June 2021

(1) Background: Glioblastoma (GBM) is the most frequent cerebral tumor. It almost always relapses and there is no validated treatment for second-line GBM. We proposed the coencapsulation of fisetin and cisplatin into liposomes, aiming to (i) obtain a synergistic effect by combining the anti-angiogenic effect of fisetin with the cytotoxic effect of cisplatin, and (ii) administrate fisetin, highly insoluble in water. The design of a liposomal formulation able to encapsulate, retain and deliver both drugs appeared a challenge. (2) Methods: Liposomes with increasing ratios of cholesterol/DOPC were prepared and characterized in term of size, PDI and stability. The incorporation of fisetin was explored using DSC. The antiangiogneic and cytotoxic activities of the selected formulation were assayed in vitro. (3) Results: We successfully developed an optimized liposomal formulation incorporating both drugs, composed by DOPC/cholesterol/DODA-GLY-PEG2000 at a molar ratio of 75.3/20.8/3.9, with a diameter of 173 ± 8 nm (PDI = 0.12 ± 0.01) and a fisetin and cisplatin drug loading of 1.7 ± 0.3% and 0.8 ± 0.1%, respectively, with a relative stability over time. The maximum incorporation of fisetin into the bilayer was determined at 3.2% w/w. Then, the antiangiogenic activity of fisetin was maintained after encapsulation. The formulation showed an additive effect of cisplatin and fisetin on GBM cells; (4) Conclusions: The developed co-loaded formulation was able to retain the activity of fisetin, was effective against GBM cells and is promising for further in vivo experimentations.
Assessing the Potential of Molecular Imaging for Myelin Quantification in Organotypic Cultures
Authors: Egimendia Ander , Carregal-Romero Susana , Osorio-Querejeta Iñaki , Padro Daniel , Ruiz-Cabello Jesús , Otaegui David , Ramos-Cabrer Pedro
Published: June 2021

Ex vivo models for the noninvasive study of myelin-related diseases represent an essential tool to understand the mechanisms of diseases and develop therapies against them. Herein, we assessed the potential of multimodal imaging traceable myelin-targeting liposomes to quantify myelin in organotypic cultures. Methods: MRI testing was used to image mouse cerebellar tissue sections and organotypic cultures. Demyelination was induced by lysolecithin treatment. Myelin-targeting liposomes were synthetized and characterized, and their capacity to quantify myelin was tested by fluorescence imaging. Results: Imaging of freshly excised tissue sections ranging from 300 µm to 1 mm in thickness was achieved with good contrast between white (WM) and gray matter (GM) using T2w MRI. The typical loss of stiffness, WM structures, and thickness of organotypic cultures required the use of diffusion-weighted methods. Designed myelin-targeting liposomes allowed for semiquantitative detection by fluorescence, but the specificity for myelin was not consistent between assays due to the unspecific binding of liposomes. Conclusions: With respect to the sensitivity, imaging of brain tissue sections and organotypic cultures by MRI is feasible, and myelin-targeting nanosystems are a promising solution to quantify myelin ex vivo. With respect to specificity, fine tuning of the probe is required. Lipid-based systems may not be suitable for this goal, due to unspecific binding to tissues.
RETRACTED: Development and Optimization of Luliconazole Spanlastics to Augment the Antifungal Activity against Candida albicans
Authors: Alhakamy Nabil , Al-Rabia Mohammed , Md Shadab , Sirwi Alaa , Khayat Selwan , AlOtaibi Sahar , Hakami Raghad , Al Sadoun Hadeel , Eldakhakhny Basmah , Abdulaal Wesam , Aldawsari Hibah , Badr-Eldin Shaimaa , Elfaky Mahmoud
Published: June 2021

Luliconazole is a new topical imidazole antifungal drug for the treatment of skin infections. It has low solubility and poor skin penetration which limits its therapeutic applications. In order to improve its therapeutic efficacy, spanlastics nanoformulation was developed and optimized using a combined mixture-process variable design (CMPV). The optimized formulation was converted into a hydrogel formula to enhance skin penetration and increase the efficacy in experimental cutaneous Candida albicans infections in Swiss mice wounds. The optimized formulation was generated at percentages of Span and Tween of 48% and 52%, respectively, and a sonication time of 6.6 min. The software predicted that the proposed formulation would achieve a particle size of 50 nm with a desirability of 0.997. The entrapment of luliconazole within the spanlastics carrier showed significant (p < 0.0001) antifungal efficacy in the immunocompromised Candida-infected Swiss mice without causing any irritation, when compared to the luliconazole treated groups. The microscopic observation showed almost complete removal of the fungal colonies on the skin of the infected animals (0.2 ± 0.05 log CFU), whereas the control animals had 0.2 ± 0.05 log CFU. Therefore, luliconazole spanlastics could be an effective formulation with improved topical delivery for antifungal activity against C. albicans.
Understanding and Avoiding AI Failures: A Practical Guide
Authors: Williams Robert , Yampolskiy Roman
Published: June 2021

As AI technologies increase in capability and ubiquity, AI accidents are becoming more common. Based on normal accident theory, high reliability theory, and open systems theory, we create a framework for understanding the risks associated with AI applications. This framework is designed to direct attention to pertinent system properties without requiring unwieldy amounts of accuracy. In addition, we also use AI safety principles to quantify the unique risks of increased intelligence and human-like qualities in AI. Together, these two fields give a more complete picture of the risks of contemporary AI. By focusing on system properties near accidents instead of seeking a root cause of accidents, we identify where attention should be paid to safety for current generation AI systems.
Phytochemical Characterization of Phoradendron bollanum and Viscum album subs. austriacum as Mexican Mistletoe Plants with Antimicrobial Activity
Authors: García-García José Daniel , Anguiano-Cabello Julia Cecilia , Arredondo-Valdés Roberto , Candido del Toro Claudio Alexis , Martínez-Hernández José Luis , Segura-Ceniceros Elda Patricia , Govea-Salas Mayela , González-Chávez Mónica Lizeth , Ramos-González Rodolfo , Esparza-González Sandra Cecilia , Ascacio-Valdés Juan Alberto , López-Badillo Claudia Magdalena , Ilyina Anna
Published: June 2021

In Mexico, mistletoes have several applications in traditional medicine due to the great variety of compounds with biological activities that have not been characterized to date. The goals of the present study are to analyze the composition of minerals and phytochemical compounds in Mexican mistletoes Phoradendron bollanum and Viscum album subs. austriacum qualitatively and quantitatively, identify the compounds using HPLC-MS, and assess the antimicrobial potential in phytopathogenic microorganism control. Mineral content was evaluated with X-ray fluorescence. Three types of extracts were prepared: ethanol, water, and aqueous 150 mM sodium chloride solution. Characterization was carried out using qualitative tests for phytochemical compound groups, analytical methods for proteins, reducing sugars, total phenol, flavonoids quantification, and HPLC-MS for compound identification. The antimicrobial activity of mistletoe’s liquid extracts was evaluated by microplate assay. K and Ca minerals were observed in both mistletoes. A qualitative test demonstrated alkaloids, carbohydrates, saponins, flavonoids, tannins, and quinones. Ethanolic extract showed flavonoids, 3845 ± 69 and 3067 ± 17.2 mg QE/g for Phoradendron bollanum and Viscum album subs. austriacum, respectively, while aqueous extracts showed a total phenol content of 65 ± 6.9 and 90 ± 1.19 mg GAE/g Phoradendron bollanum and Viscum album subs. austriacum, respectively. HPLC-MS identified largely hydroxycinnamic acids and methoxycinnamic acids. Clavibacter michiganenses was successfully inhibited by aqueous extract of both mistletoes.
Pinus Species as Prospective Reserves of Bioactive Compounds with Potential Use in Functional Food—Current State of Knowledge
Authors: Dziedziński Marcin , Kobus-Cisowska Joanna , Stachowiak Barbara
Published: June 2021

The pine (Pinus L.) is the largest and most heteromorphic plant genus of the pine family (Pinaceae Lindl.), which grows almost exclusively in the northern hemisphere. The demand for plant-based remedies, supplements and functional food is growing worldwide. Although pine-based products are widely available in many parts of the world, they are almost absent as food ingredients. The literature shows the beneficial effects of pine preparations on human health. Despite the wide geographical distribution of pine trees in the natural environment, there are very few data in the literature on the widespread use of pine in food technology. This study aims to present, characterise and evaluate the content of phytochemicals in pine trees, including shoots, bark and conifer needles, as well as to summarise the available data on their health-promoting and functional properties, and the potential of their use in food and the pharmaceutical industry to support health. Various species of pine tree contain different compositions of bioactive compounds. Regardless of the solvent, method, pine species and plant part used, all pine extracts contain a high number of polyphenols. Pine tree extracts exhibit several described biological activities that may be beneficial to human health. The available examples of the application of pine elements in food are promising. The reuse of residual pine elements is still limited compared to its potential. In this case, it is necessary to conduct more research to find and develop new products and applications of pine residues and by-products.
Phytochemical Content, Antioxidant, Alpha-Glucosidase Inhibitory and Antibacterial Activities of Spineless Cactus Pear Cultivars
Authors: Mabotja Mologadi B. , Venter Sonja L. , Du Plooy Christian P. , Kudanga Tukayi , Amoo Stephen O.
Published: June 2021

Variation in cultivars can influence plant biological activities. This study aimed to identify superior cultivars while determining the variability in the phytochemical content, antioxidant, alpha-glucosidase inhibitory and antibacterial activities of cladode extracts from selected spineless Burbank cactus pear (Opuntia ficus-indica and Opuntia robusta) cultivars. Total phenolic and flavonoid contents were determined using the Folin-Ciocalteu and aluminum chloride spectrophotometric methods, respectively. Antioxidant activity was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene linoleic acid assays. Alpha-glucosidase inhibition was determined using a spectrophotometric method and antibacterial activity using a non-polar (petroleum ether) and polar (50% methanol) extracts against two Gram-positive and two Gram-negative bacteria. Significant variation in phytochemical content, antioxidant, antidiabetic and antibacterial activities was observed amongst the cultivars. Alpha-glucosidase inhibitory activity varied widely with IC50 values ranging from 0.06 to 1.85 mg/mL. Radical scavenging activity of Polypoly cultivar was about seven fold higher than that recorded in other cultivars with low activity. Turpin and Berg x Mexican cultivars had the highest total phenolic and flavonoid contents, whilst the non-polar extract of Turpin also exhibited higher antibacterial activity against Bacillus subtilis and Escherichia coli. Sicilian Indian Fig was amongst the cultivars with a higher antioxidant activity, whilst also showing a strong inhibition against B. subtilis and E. coli. Polypoly cultivar demonstrated strong antioxidant and antidiabetic activities while its polar extract showed the highest total antibacterial activity against B. subtilis. The cultivar Malta was superior in terms of its antibacterial potency and efficacy against B. subtilis, Staphylococcus aureus and E. coli. The potential of using spineless cactus pear cladodes as a functional food with antioxidant, antidiabetic and antibacterial properties against pathogenic food spoilage bacteria in place of synthetic compounds was established. The significance of cultivar selection to increase this potential was highlighted.
Exogenous Putrescine Enhances Salt Tolerance and Ginsenosides Content in Korean Ginseng (Panax ginseng Meyer) Sprouts
Authors: Islam Md. Jahirul , Ryu Byeong Ryeol , Azad Md. Obyedul Kalam , Rahman Md. Hafizur , Rana Md. Soyel , Lim Jung-Dae , Lim Young-Seok
Published: June 2021

The effect of exogenously applied putrescine (Put) on salt stress tolerance was investigated in Panax ginseng. Thirty-day-old ginseng sprouts were grown in salinized nutrient solution (150 mM NaCl) for five days, while the control sprouts were grown in nutrients solution. Putrescine (0.3, 0.6, and 0.9 mM) was sprayed on the plants once at the onset of salinity treatment, whereas control plants were sprayed with water only. Ginseng seedlings tested under salinity exhibited reduced plant growth and biomass production, which was directly interlinked with reduced chlorophyll and chlorophyll fluorescence due to higher reactive oxygen species (hydrogen peroxide; H2O2) and lipid peroxidation (malondialdehyde; MDA) production. Application of Put enhanced accumulation of proline, total soluble carbohydrate, total soluble sugar and total soluble protein. At the same time, activities of antioxidant enzymes like superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase in leaves, stems, and roots of ginseng seedlings were increased. Such modulation of physio-biochemical processes reduced the level of H2O2 and MDA, which indicates a successful adaptation of ginseng seedlings to salinity stress. Moreover, protopanaxadiol (PPD) ginsenosides enhanced by both salinity stress and exogenous Put treatment. On the other hand, protopanaxatriol (PPT) ginsenosides enhanced in roots and reduced in leaves and stems under salinity stress condition. In contrast, they enhanced by exogenous Put application in all parts of the plants for most cases, also evidenced by principal component analysis. Collectively, our findings provide an important prospect for the use of Put in modulating salinity tolerance and ginsenosides content in ginseng sprouts.
Role of Engineered Carbon Nanoparticles (CNPs) in Promoting Growth and Metabolism of Vigna radiata (L.) Wilczek: Insights into the Biochemical and Physiological Responses
Authors: Shekhawat Gyan Singh , Mahawar Lovely , Rajput Priyadarshani , Rajput Vishnu D. , Minkina Tatiana , Singh Rupesh Kumar
Published: June 2021

Despite the documented significance of carbon-based nanomaterials (CNMs) in plant development, the knowledge of the impact of carbon nanoparticles (CNPs) dosage on physiological responses of crop plants is still scarce. Hence, the present study investigates the concentration-dependent impact of CNPs on the morphology and physiology of Vigna radiata. Crop seedlings were subjected to CNPs at varying concentrations (25 to 200 µM) in hydroponic medium for 96 h to evaluate various physiological parameters. CNPs at an intermediate concentration (100 to 150 µM) favor the growth of crops by increasing the total chlorophyll content (1.9-fold), protein content (1.14-fold) and plant biomass (fresh weight: 1.2-fold, dry weight: 1.14-fold). The highest activity of antioxidants (SOD, GOPX, APX and proline) was also recorded at these concentrations, which indicates a decline in ROS level at 100 µM. At the highest CNPs treatment (200 µM), aggregation of CNPs was observed more on the root surface and accumulated in higher concentrations in the plant tissues, which limits the absorption and translocation of nutrients to plants, and hence, at these concentrations, the oxidative damage imposed by CNPs is evaded with the rise in activity of antioxidants. These findings show the importance of CNPs as nano-fertilizers that not only improve plant growth by their slow and controlled release of nutrients, but also enhance the stress-tolerant and phytoremediation efficiency of plants in the polluted environment due to their enormous absorption potential.
Hyaluronic Acid-Based Scaffolds as Potential Bioactive Wound Dressings
Authors: Alven Sibusiso , Aderibigbe Blessing A.
Published: June 2021

The negative factors that result in delayed and prolonged wound healing process include microbial pathogens, excess wound exudates, underlying conditions, smoking, obesity, etc. Most of the currently used wound dressings demonstrate an inadequate capacity to treat wounds resulting from the factors mentioned above. The commonly used wound dressings include hydrogels, films, hydrocolloids, foams, fibers, sponges, dermal patches, bandages, etc. These wound dressings can be loaded with various types of bioactive agents (e.g., antibiotics, nanoparticles, anti-inflammatory drugs, etc.) to improve their therapeutic outcomes. Biopolymers offer interesting properties suitable for the design of wound dressings. This review article will be based on hyaluronic-acid-based scaffolds loaded with therapeutic agents for the treatment of wounds.
Elucidation of Mechanical, Physical, Chemical and Thermal Properties of Microbial Composite Films by Integrating Sodium Alginate with Bacillus subtilis sp.
Authors: Wai Chun Charles Ng , Tajarudin Husnul Azan , Ismail Norli , Azahari Baharin , Mohd Zaini Makhtar Muaz
Published: June 2021

Materials are the foundation in human development for improving human standards of life. This research aimed to develop microbial composite films by integrating sodium alginate with Bacillus subtilis. Sodium alginate film was fabricated as control. The microbial composite films were fabricated by integrating 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 g of Bacillus subtilis into the sodium alginate. Evaluations were performed on the mechanical, physical, chemical and thermal properties of the films. It was found that films reinforced with Bacillus subtilis significantly improved all the mentioned properties. Results show that 0.5 g microbial composite films had the highest tensile strength, breaking strain and toughness, which were 0.858 MPa, 87.406% and 0.045 MJ/m3, respectively. The thickness of the film was 1.057 mm. White light opacity, black light opacity and brightness values were 13.65%, 40.55% and 8.19%, respectively. It also had the highest conductivity, which was 37 mV, while its water absorption ability was 300.93%. Furthermore, it had a higher melting point of 218.94 °C and higher decomposition temperature of 252.69 °C. SEM also showed that it had filled cross-sectional structure and smoother surface compared to the sodium alginate film. Additionally, FTIR showed that 0.5 g microbial composite films possessed more functional groups at 800 and 662 cm-1 wavenumbers that referred to C–C, C–OH, C–H ring and side group vibrations and C-OH out-of-plane bending, respectively, which contributed to the stronger bonds in the microbial composite film. Initial conclusions depict the potential of Bacillus subtilis to be used as reinforcing material in the development of microbial composite films, which also have the prospect to be used in electronic applications. This is due to the conductivity of the films increasing as Bacillus subtilis cell mass increases.
Antibacterial Activity of Polymer Nanocomposites Incorporating Graphene and Its Derivatives: A State of Art
Authors: Díez-Pascual Ana M. , Luceño-Sánchez José A.
Published: June 2021

The incorporation of carbon-based nanostructures into polymer matrices is a relevant strategy for producing novel antimicrobial materials. By using nanofillers of different shapes and sizes, and polymers with different characteristics, novel antimicrobial nanocomposites with synergistic properties can be obtained. This article describes the state of art in the field of antimicrobial polymeric nanocomposites reinforced with graphene and its derivatives such as graphene oxide and reduced graphene oxide. Taking into account the vast number of articles published, only some representative examples are provided. A classification of the different nanocomposites is carried out, dividing them into acrylic and methacrylic matrices, biodegradable synthetic polymers and natural polymers. The mechanisms of antimicrobial activity of graphene and its derivatives are also reviewed. Finally, some applications of these antimicrobial nanocomposites are discussed. We aim to enhance understanding in the field and promote further work on the development of polymer-based antimicrobial nanocomposites incorporating graphene-based nanomaterials.
Development of a Care Labelling Process for Compression Stockings Based on Natural (Cotton) Fibers
Authors: Candan Cevza , Nergis Banu , Cimilli Duru Sena , Koyuncu Bilge
Published: June 2021

This study is to investigate to what extent the performance of compression stockings with cotton components deteriorates after repeated washing processes. Four compression stockings having at least one cotton constituent yarn and two all-nylon stockings as reference samples were produced under controlled commercial conditions. After analysing the data obtained, a care labelling process for the compression socks with cotton components was developed such that they can preserve their compression properties over successive laundering treatments.
Easy-to-Make Polymer Hydrogels by UV-Curing for the Cleaning of Acrylic Emulsion Paint Films
Authors: Cárdaba Irene , Porcarelli Luca , Gallastegui Antonela , Mecerreyes David , Maguregui Miren Itxaso
Published: June 2021

The cleaning of acrylic emulsion paint surfaces poses a great challenge in the conservation field, due to their high water sensitivity. In this article, we present easy-to-make polymer hydrogels, made by UV-photopolymerization, that show excellent cleaning properties. The formulation of hydrogels obtained by UV-curing and their performance as dry cleaners for acrylic paints was investigated. First, different hydrogel formulations based on functional acrylic monomers were used to formulate a series of UV cross-linked hydrogels by fast UV photopolymerization. Their effectiveness on surface dirt removal was investigated by SEM microscopy and colorimetry. The hydrogels showed excellent cleaning properties and controlled water release, and they still performed satisfactorily after several cleaning uses. The obtained UV-hydrogels were compared to the well-known agar gels, showing benefits in terms of reducing excess water. This article shows that easy-to-make UV-cured hydrogels are an efficient tool for the cleaning of surface dirt from water-sensitive paintings, overcoming the limits of traditional cleaning methods.
Corn Starch-Chitosan Nanocomposite Film Containing Nettle Essential Oil Nanoemulsions and Starch Nanocrystals: Optimization and Characterization
Authors: Kalateh-Seifari Fatemeh , Yousefi Shima , Ahari Hamed , Hosseini Seyed Hedayat
Published: June 2021

In the current study, nanocomposite films were produced based on corn starch:chitosan (CS:CH) biopolymers and the films were reinforced with nettle essential oil nanoemulsions (NEONEs) and starch nanocrystals (SNCs) to improve their physicochemical and mechanical properties. CS: CH at 70:30, 50:50, and 30:70 (w/w) ratios; SNCs at 2, 4, and 6% (w/w), and NEONEs at 0.5, 1, and 1.5% (w/w) were selected as variables. Then the various physical and mechanical attributes of chitosan-starch blended film containing SNCs and NEONEs were optimized using response surface methodology. The desirability function technique for the second-order polynomial models revealed that the following results could be achieved as the optimized treatment: water solubility of 51.56%; water absorption capacity of 128.75%; surface color of L (89.60), a (0.96), and b (1.90); water vapor permeability of 0.335 g/s Pa m, oxygen permeability of 2.60 cm3 μm/m2 d kPa; thickness of 154.41 µm, elongation at break of 53.54%; and tensile strength of 0.20 MPa at CS:CH of 38:62, SNC of 6.0%, and NEONEs of 0.41%. The nanocomposite film obtained can be employed as a novel biofunctional film with boosted physical mechanical and physical characteristics for food packaging applications.
How to Sterilize Polylactic Acid Based Medical Devices?
Authors: Pérez Davila Sara , González Rodríguez Laura , Chiussi Stefano , Serra Julia , González Pío
Published: June 2021

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented.