bluuebunny/crossref_metadata_2025 huggingface dataset:
New Amino Acid Schiff Bases as Anticancer Agents via Potential Mitochondrial Complex I-Associated Hexokinase Inhibition and Targeting AMP-Protein Kinases/mTOR Signaling Pathway
Authors: Noser Ahmed A. , Abdelmonsef Aboubakr H. , El-Naggar Mohamed , Salem Maha M.
Published: September 2021

Two series of novel amino acid Schiff base ligands containing heterocyclic moieties, such as quinazolinone 3–11 and indole 12–20 were successfully synthesized and confirmed by spectroscopic techniques and elemental analysis. Furthermore, all compounds were investigated in silico for their ability to inhibit mitochondrial NADH: ubiquinone oxidoreductase (complex I) by targeting the AMPK/mTOR signaling pathway and inhibiting hexokinase, a key glycolytic enzyme to prevent the Warburg effect in cancer cells. This inhibitory pathway may be an effective strategy to cause cancer cell death due to an insufficient amount of ATP. Our results revealed that, out of 18 compounds, two (11 and 20) were top-ranked as they exhibited the highest binding energies of −8.8, −13.0, −7.9, and −10.0 kcal/mol in the docking analysis, so they were then selected for in vitro assessment. Compound 11 promoted the best cytotoxic effect on MCF-7 with IC50 = 64.05 ± 0.14 μg/mL (0.135 mM) while compound 20 exhibited the best cytotoxic effect on MDA-231 with IC50 = 46.29 ± 0.09 μg/mL (0.166 mM) Compounds 11 and 20 showed significant activation of AMPK protein and oxidative stress, which led to elevated expression of p53 and Bax, reduced Bcl-2 expression, and caused cell cycle arrest at the sub-G0/G1 phase. Moreover, compounds 11 and 20 showed significant inhibition of the mTOR protein, which led to the activation of aerobic glycolysis for survival. This alternative pathway was also blocked as compounds 11 and 20 showed significant inhibitory effects on the hexokinase enzyme. These findings demonstrate that compounds 11 and 20 obeyed Lipinski’s rule of five and could be used as privileged scaffolds for cancer therapy via their potential inhibition of mitochondrial complex I-associated hexokinase.
Analysis of Cannabinoids and Metabolites in Dried Urine Spots (DUS)
Authors: Moretti Matteo , Freni Francesca , Carelli Claudia , Previderé Carlo , Grignani Pierangela , Vignali Claudia , Cobo-Golpe Maria , Morini Luca
Published: September 2021

Dried urine spots (DUS) represent a potential alternative sample storage for forensic toxicological analysis. The aim of the current study was to develop and validate a liquid chromatographic tandem mass spectrometric procedure for the detection and quantitative determination of cannabinoids and metabolites in DUS. A two-step extraction was performed on DUS and urine samples. An LC-MS/MS system was operated in multiple reaction monitoring and positive polarization mode. The method was checked for sensitivity, specificity, linearity, accuracy, precision, recovery, matrix effects and carryover. The method was applied to 70 urine samples collected from healthy volunteers and drug addicts undergoing withdrawal treatment. The method was successfully developed for DUS. LODs lower than 2.0 ng/mL were obtained for all the monitored substances. All the validation parameters fulfilled the acceptance criteria either for DUS or urine. Among the real samples, 45 cases provided positive results for at least one compound. A good quali-quantitative agreement was obtained between DUS and urine. A good stability of THC, THCCOOH and THCCOOH-gluc was observed after a 24 h storage, in contrast to previously published results. DUS seems to provide a good alternative storage condition for urine that should be checked for the presence of cannabinoids and metabolites.
Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors
Authors: Osman Doaa A. , Macías Mario A. , Al-Wahaibi Lamya H. , Al-Shaalan Nora H. , Zondagh Luke S. , Joubert Jacques , Garcia-Granda Santiago , El-Emam Ali A.
Published: September 2021

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound 2 crystallizes in the triclinic P-1 space group, while compounds 1 and 3 crystallize in the same monoclinic P21/c space group. Since the only difference between them is the para substitution on the aryl group, the electronic nature of these NO2 and halogen groups seems to have no influence over the formation of the solid. However, a probable correlation with the size of the groups is not discarded due to the similar intermolecular disposition between the NO2/Cl substituted molecules. Despite the similarities, CE-B3LYP energy model calculations show that pairwise interaction energies vary between them, and therefore the total packing energy is affected. HOMO-LUMO calculated energies show that the NO2 group influences the reactivity properties characterizing the molecule as soft and with the best disposition to accept electrons. Further, in silico studies predicted that the compounds might be able to inhibit the 11β-HSD1 enzyme, which is implicated in obesity and diabetes. Self- and cross-docking experiments revealed that a number of non-native 11β-HSD1 inhibitors were able to accurately dock within the 11β-HSD1 X-ray structure 4C7J. The molecular docking of the adamantane-linked 1,2,4-triazoles have similar predicted binding affinity scores compared to the 4C7J native ligand 4YQ. However, they were unable to form interactions with key active site residues. Based on these docking results, a series of potentially improved compounds were designed using computer aided drug design tools. The docking results of the new compounds showed similar predicted 11β-HSD1 binding affinity scores as well as interactions to a known potent 11β-HSD1 inhibitor.
Ergosta-7,9(11),22-trien-3β-ol Rescues AD Deficits by Modulating Microglia Activation but Not Oxidative Stress
Authors: Liu Hsin-Ping , Kuo Yueh-Hsiung , Cheng Jack , Chang Li-Zhong , Chang Meng-Shiun , Su Li-Wen , Chuang Tsai-Ni , Lin Wei-Yong
Published: September 2021

Ergosta-7,9(11),22-trien-3β-ol (EK100) was isolated from the Taiwan-specific medicinal fungus Antrodia camphorata, which is known for its health-promotion and anti-aging effects in folk medicine. Alzheimer’s disease (AD) is a major aging-associated disease. We investigated the efficacy and potential mechanism of ergosta-7,9(11),22-trien-3β-ol for AD symptoms. Drosophila with the pan-neuronal overexpression of human amyloid-β (Aβ) was used as the AD model. We compared the life span, motor function, learning, memory, oxidative stress, and biomarkers of microglia activation and inflammation of the ergosta-7,9(11),22-trien-3β-ol-treated group to those of the untreated control. Ergosta-7,9(11),22-trien-3β-ol treatment effectively improved the life span, motor function, learning, and memory of the AD model compared to the untreated control. Biomarkers of microglia activation and inflammation were reduced, while the ubiquitous lipid peroxidation, catalase activity, and superoxide dismutase activity remained unchanged. In conclusion, ergosta-7,9(11),22-trien-3β-ol rescues AD deficits by modulating microglia activation but not oxidative stress.
Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
Authors: Wudtiwai Benjawan , Makeudom Anupong , Krisanaprakornkit Suttichai , Pothacharoen Peraphan , Kongtawelert Prachya
Published: September 2021

Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer.
Carbon Nanostructures Doped with Transition Metals for Pollutant Gas Adsorption Systems
Authors: Ramirez-de-Arellano J. , Canales M. , Magaña L.
Published: September 2021

The adsorption of molecules usually increases capacity and/or strength with the doping of surfaces with transition metals; furthermore, carbon nanostructures, i.e., graphene, carbon nanotubes, fullerenes, graphdiyne, etc., have a large specific area for gas adsorption. This review focuses on the reports (experimental or theoretical) of systems using these structures decorated with transition metals for mainly pollutant molecules’ adsorption. Furthermore, we aim to present the expanding application of nanomaterials on environmental problems, mainly over the last 10 years. We found a wide range of pollutant molecules investigated for adsorption in carbon nanostructures, including greenhouse gases, anticancer drugs, and chemical warfare agents, among many more.
Altered Volcanic Tuffs from Los Frailes Caldera. A Study of Their Pozzolanic Properties
Authors: Costafreda Jorge Luis , Martín Domingo Alfonso , Presa Leticia , Parra José Luis
Published: September 2021

This work presents the results of the study of the physical, chemical, mineralogical and pozzolanic properties of the altered volcanic tuffs (AVT) that lie in the Los Frailes caldera, south of the Iberian Peninsula, and demonstrates their qualities as pozzolans for the manufacturing of mortars and pozzolanic cements of high mechanical strength. The main objective of this research is to show to what extent the AVTs can replace portland cement (PC) in mortars, with standardised proportions of 75:25% and 70:30% (PC-AVT). To achieve these objectives, three AVT samples were studied by a petrographic analysis of thin section (PATS), DRX, FRX and MEB. The pozzolanic properties were determined by three methods: electrical conductivity (ECT), chemical pozzolanicity tests (CPT) at 8 and 15 days and mechanical strength tests (MS) of the specimens at 2, 7, 28 and 90 days. Studies of a PATS, DRX, FRX and MEB showed that the AVT samples’ constitutions are complex where smectite (montmorillonite), mordenite, quartz, halloysite, illite, kaolinite, volcanic glass and lithic fragments coexist. The results of the ECT and CPT tests confirmed the pozzolanic properties of the samples analysed and proved an increase in mechanical strength from 2 to 90 days of testing.
Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors
Authors: Buron Frédéric , Rodrigues Nuno , Saurat Thibault , Hiebel Marie Aude , Bourg Stéphane , Bonnet Pascal , Nehmé Reine , Morin Philippe , Percina Nathalie , Corret Justine , Vallée Béatrice , le Guevel Remy , Jourdan Marie-Lise , Bénédetti Hélène , Routier Sylvain
Published: September 2021

This work describes the synthesis, enzymatic activities on PI3K and mTOR, in silico docking and cellular activities of various uncommon 2,4,7 trisubstituted pyrido[3,2-d]pyrimidines. The series synthesized offers a chemical diversity in C-7 whereas C-2 (3-hydroxyphenyl) and C-4 groups (morpholine) remain unchanged, in order to provide a better understanding of the molecular determinants of PI3K selectivity or dual activity on PI3K and mTOR. Some C-7 substituents were shown to improve the efficiency on kinases compared to the 2,4-di-substituted pyrimidopyrimidine derivatives used as references. Six novel derivatives possess IC50 values on PI3Kα between 3 and 10 nM. The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway.
Anti-Inflammatory Effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and NF-κB Signaling Pathways
Authors: Kang Jin-Kyu , Chung You-Chul , Hyun Chang-Gu
Published: September 2021

Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE2 without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.
Nano-Hydroxyapatite vs. Xenografts: Synthesis, Characterization, and In Vitro Behavior
Authors: Dumitrescu Cristina Rodica , Neacsu Ionela Andreea , Surdu Vasile Adrian , Nicoara Adrian Ionut , Iordache Florin , Trusca Roxana , Ciocan Lucian Toma , Ficai Anton , Andronescu Ecaterina
Published: September 2021

This research focused on the synthesis of apatite, starting from a natural biogenic calcium source (egg-shells) and its chemical and morpho-structural characterization in comparison with two commercial xenografts used as a bone substitute in dentistry. The synthesis route for the hydroxyapatite powder was the microwave-assisted hydrothermal technique, starting from annealed egg-shells as the precursor for lime and di-base ammonium phosphate as the phosphate precursor. The powders were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDAX), transmission electron microscopy (TEM), X-ray fluorescence spectroscopy (XRF), and cytotoxicity assay in contact with amniotic fluid stem cell (AFSC) cultures. Compositional and structural similarities or differences between the powder synthesized from egg-shells (HA1) and the two commercial xenograft powders—Bio-Oss®, totally deproteinized cortical bovine bone, and Gen-Os®, partially deproteinized porcine bone—were revealed. The HA1 specimen presented a single mineral phase as polycrystalline apatite with a high crystallinity (Xc 0.92), a crystallite size of 43.73 nm, preferential growth under the c axes (002) direction, where it mineralizes in bone, a nano-rod particle morphology, and average lengths up to 77.29 nm and diameters up to 21.74 nm. The surface of the HA1 nanoparticles and internal mesopores (mean size of 3.3 ± 1.6 nm), acquired from high-pressure hydrothermal maturation, along with the precursor’s nature, could be responsible for the improved biocompatibility, biomolecule adhesion, and osteoconductive abilities in bone substitute applications. The cytotoxicity assay showed a better AFSC cell viability for HA1 powder than the commercial xenografts did, similar oxidative stress to the control sample, and improved results compared with Gen-Os. The presented preliminary biocompatibility results are promising for bone tissue regeneration applications of HA1, and the study will continue with further tests on osteoblast differentiation and mineralization.
Impact of a School-Based Gardening, Cooking, Nutrition Intervention on Diet Intake and Quality: The TX Sprouts Randomized Controlled Trial
Authors: Landry Matthew J. , van den Berg Alexandra E. , Hoelscher Deanna M. , Asigbee Fiona M. , Vandyousefi Sarvenaz , Ghaddar Reem , Jeans Matthew R. , Waugh Lyndsey , Nikah Katie , Sharma Shreela V. , Davis Jaimie N.
Published: September 2021

School gardens have become common school-based health promotion strategies to enhance dietary behaviors in the United States. The goal of this study was to examine the effects of TX Sprouts, a one-year school-based gardening, cooking, and nutrition cluster randomized controlled trial, on students’ dietary intake and quality. Eight schools were randomly assigned to the TX Sprouts intervention and eight schools to control (i.e., delayed intervention) over three years (2016–2019). The intervention arm received: formation and training of Garden Leadership Committees; a 0.25-acre outdoor teaching garden; 18 student lessons including gardening, nutrition, and cooking activities, taught weekly in the teaching garden during school hours; and nine parent lessons, taught monthly. Dietary intake data via two 24 h dietary recalls (24 hDR) were collected on a random subsample (n = 468). Dietary quality was calculated using the Healthy Eating Index 2015 (HEI-2015). The intervention group compared to control resulted in a modest increase in protein intake as a percentage of total energy (0.4% vs. −0.3%, p = 0.021) and in HEI-2015 total vegetables component scores (+4% vs. −2%, p = 0.003). When stratified by ethnicity/race, non-Hispanic children had a significant increase in HEI-2015 total vegetable scores in the intervention group compared to the control group (+4% vs. −8%, p = 0.026). Both the intervention and control groups increased added sugar intake; however, to a lesser extent within the intervention group (0.3 vs. 2.6 g/day, p = 0.050). School-based gardening, cooking, and nutrition interventions can result in significant improvements in dietary intake. Further research on ways to scale and sustain nutrition education programs in schools is warranted. The trial is registered at ClinicalTrials.gov (NCT02668744).
Association of Dietary Vitamin D Intake, Serum 25(OH)D3, 25(OH)D2 with Cognitive Performance in the Elderly
Authors: Wang RuTong , Wang Weijing , Hu Ping , Zhang Ronghui , Dong Xue , Zhang Dongfeng
Published: September 2021

Background: As life expectancy increases, cognitive performance decline in the elderly has become one of the major global challenges. We aimed to evaluate the association of dietary vitamin D (VD), serum 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2), and total 25-hydroxyvitamin (25(OH)D) concentration with cognitive performance in older Americans. Methods: The data from the National Health and Nutrition Examination Survey (NHANES), 2011–2014 was used. The cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). A binary logistic regression model was applied to evaluate the association between VD and cognitive performance, and restricted cubic spline model was adopted to evaluate the dose–response relationship. Results: While comparing to the lowest dietary VD intake group, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest dietary VD intake group were 0.51 (0.36–0.72) for the Animal Fluency test score and 0.45 (0.31–0.66) for DSST score, respectively; and those of serum total 25(OH)D and 25(OH)D3 concentration were 0.68 (0.47–0.97) and 0.62 (0.44–0.86) for DSST score. L-shaped relationships were identified for dietary VD intake, serum total 25(OH)D and 25(OH)D3 concentration with cognition performance. The associations between dietary VD intake, serum total 25(OH)D and cognitive performance were non-significant when stratified by gender. Conclusions: The study indicates that dietary VD intake, serum total 25(OH)D and 25(OH)D3 concentration were positively associated with cognitive performance. Further studies are needed to clarify the possible effects of dietary VD intake and serum 25(OH)D2, 25(OH)D3 on cognitive performance.
Treatment of Human Babesiosis: Then and Now
Authors: Renard Isaline , Ben Mamoun Choukri
Published: September 2021

Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. With its increasing incidence worldwide and the risk of human-to-human transmission through blood transfusion, babesiosis is becoming a rising public health concern. The current arsenal for the treatment of human babesiosis is limited and consists of combinations of atovaquone and azithromycin or clindamycin and quinine. These combination therapies were not designed based on biological criteria unique to Babesia parasites, but were rather repurposed based on their well-established efficacy against other apicomplexan parasites. However, these compounds are associated with mild or severe adverse events and a rapid emergence of drug resistance, thus highlighting the need for new therapeutic strategies that are specifically tailored to Babesia parasites. Herein, we review ongoing babesiosis therapeutic and management strategies and their limitations, and further review current efforts to develop new, effective, and safer therapies for the treatment of this disease.
Mapping the Spatial Distribution of the Rumen Fluke Calicophoron daubneyi in a Mediterranean Area
Authors: Bosco Antonio , Nocerino Martina , Santaniello Mirella , Maurelli Maria Paola , Cringoli Giuseppe , Rinaldi Laura
Published: September 2021

Rumen flukes (Calicophoron daubneyi) represent a growing threat to the animal health, productivity and welfare of ruminants. The present study aimed to assess the spatial distribution of C. daubneyi infections in ruminants and to develop a predictive model of the environmental suitability for rumen flukes in a Mediterranean area. A cross-sectional coprological survey was conducted in 682 sheep, 73 goat and 307 cattle farms located in the Basilicata region (southern Italy). Faecal samples collected were analysed using the FLOTAC technique. Geographical Information Systems (GIS) and statistical models were developed to determine environmental risk factors and to delimitate the areas at highest risk of infections in small ruminants. The results showed 7.9% (95% CI 6.05–10.27) of sheep farms, 2.7% (95% CI 0.48–10.44) of goat farms and 55.0% (95% CI 49.62–60.99) of cattle farms were infected by C. daubneyi. The areas with high predicted risk were situated in the western part of the region. The soil texture, land use and the presence of streams and brooks were the variables statistically significant (p < 0.05) in explaining the C. daubneyi distribution in the study area. The study confirms the importance of geospatial technology in supporting parasite control strategies in livestock and demonstrates that a combined use of different geostatistical techniques can improve the prediction of the C. daubneyi infection risk in ruminants.
Detection of Vesicular Stomatitis Virus Indiana from Insects Collected during the 2020 Outbreak in Kansas, USA
Authors: McGregor Bethany L. , Rozo-Lopez Paula , Davis Travis M. , Drolet Barbara S.
Published: September 2021

Vesicular stomatitis (VS) is a reportable viral disease which affects horses, cattle, and pigs in the Americas. Outbreaks of vesicular stomatitis virus New Jersey serotype (VSV-NJ) in the United States typically occur on a 5–10-year cycle, usually affecting western and southwestern states. In 2019–2020, an outbreak of VSV Indiana serotype (VSV-IN) extended eastward into the states of Kansas and Missouri for the first time in several decades, leading to 101 confirmed premises in Kansas and 37 confirmed premises in Missouri. In order to investigate which vector species contributed to the outbreak in Kansas, we conducted insect surveillance at two farms that experienced confirmed VSV-positive cases, one each in Riley County and Franklin County. Centers for Disease Control and Prevention miniature light traps were used to collect biting flies on the premises. Two genera of known VSV vectors, Culicoides biting midges and Simulium black flies, were identified to species, pooled by species, sex, reproductive status, and collection site, and tested for the presence of VSV-IN RNA by RT-qPCR. In total, eight positive pools were detected from Culicoides sonorensis (1), Culicoides stellifer (3), Culicoides variipennis (1), and Simulium meridionale (3). The C. sonorensis- and C. variipennis-positive pools were from nulliparous individuals, possibly indicating transovarial or venereal transmission as the source of virus. This is the first report of VSV-IN in field caught C. stellifer and the first report of either serotype in S. meridionale near outbreak premises. These results improve our understanding of the role midges and black flies play in VSV epidemiology in the United States and broadens the scope of vector species for targeted surveillance and control.
Indian Herb-Derived Phytoconstituent-Based Antiviral, Antimicrobial and Antifungal Formulation: An Oral Rinse Candidate for Oral Hygiene and the Potential Prevention of COVID-19 Outbreaks
Authors: Sharad Shashwat , Kapur Suman
Published: September 2021

Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different lines of treatment, such as vaccines and antiviral drugs. To find the appropriate prevention/treatment, 21 plant-based ingredients (Glycyrrhizin, Withanone, Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Kaempferol, Progallin A, Gallic acid, Naringin, Quercetin, Luteolin, and Apigenin) having antiviral, antibacterial and antifungal properties were identified. We pseudo-typed SARS-CoV-2 on a lentiviral vector plasmid and tested the impact of five different herbal formulations in mammalian HEK293T cells. Viral inactivation assay showed that the natural extracts in a herb-derived phytoconstituent-based formulation, BITS-003, comprising Bacopa monnieri, Glycyerrhiza glabra, Asparagus racemosus-wild, and Nigella sativa had strong virucidal properties, inactivating enveloped viruses from 2log10 (or 99%) to >4log10 (or 99.99%). Moreover, bacterial and yeast cells treated with BITS-003 displayed reduced growth. Topical use of the formulation as a mouthwash/gargle could be effective in reducing symptoms of respiratory viral infections, with the potential to decrease the viral load in the buccal/oral cavity. This may inhibit the coronavirus spreading to the lungs of infected persons and at the same time may reduce the risk of viral transmission to other susceptible persons through micro-droplets originating from the oral cavity of the infected person.
Pyrroles as Privileged Scaffolds in the Search for New Potential HIV Inhibitors
Authors: Bianco Maria da Conceição Avelino Dias , Marinho Debora Inacio Leite Firmino , Hoelz Lucas Villas Boas , Bastos Monica Macedo , Boechat Nubia
Published: September 2021

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and remains a global health problem four decades after the report of its first case. Despite success in viral load suppression and the increase in patient survival due to combined antiretroviral therapy (cART), the development of new drugs has become imperative due to strains that have become resistant to antiretrovirals. In this context, there has been a continuous search for new anti-HIV agents based on several chemical scaffolds, including nitrogenated heterocyclic pyrrole rings, which have been included in several compounds with antiretroviral activity. Thus, this review aims to describe pyrrole-based compounds with anti-HIV activity as a new potential treatment against AIDS, covering the period between 2015 and 2020. Our research allowed us to conclude that pyrrole derivatives are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle and act with an innovative mechanism.
Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy
Authors: Han Ji-Won , Yoon Seung-Kew
Published: September 2021

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.
Quality-by-Design-Based Development of a Voxelotor Self-Nanoemulsifying Drug-Delivery System with Improved Biopharmaceutical Attributes
Authors: Buya Aristote B. , Terrasi Romano , Mbinze Jérémie K. , Muccioli Giulio G. , Beloqui Ana , Memvanga Patrick B. , Préat Véronique
Published: September 2021

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed.
Enhanced Antimicrobial Action of Chlorhexidine Loaded in Shellac Nanoparticles with Cationic Surface Functionality
Authors: Al-Obaidy Saba S. M. , Greenway Gillian M. , Paunov Vesselin N.
Published: September 2021

We report on an active nanocarrier for chlorhexidine (CHX) based on sterically stabilized shellac nanoparticles (NPs) with dual surface functionalization, which greatly enhances the antimicrobial action of CHX. The fabrication process for the CHX nanocarrier is based on pH-induced co-precipitation of CHX-DG from an aqueous solution of ammonium shellac and Poloxamer 407 (P407), which serves as a steric stabilizing agent. This is followed by further surface modification with octadecyl trimethyl ammonium bromide (ODTAB) through a solvent change to yield cationic surface functionality. In this study, we assessed the encapsulation efficiency and release kinetics of the novel nanocarrier for CHX. We further examined the antimicrobial effects of the CHX nanocarriers and their individual components in order to gain better insight into how they work, to improve their design and to explore the impacts of their dual functionalization. The antimicrobial actions of CHX loaded in shellac NPs were examined on three different proxy microorganisms: a Gram-negative bacterium (E. coli), a yeast (S. cerevisiae) and a microalgae (C. reinhardtii). The antimicrobial actions of free CHX and CHX-loaded shellac NPs were compared over the same CHX concentration range. We found that the non-coated shellac NPs loaded with CHX showed inferior action compared with free CHX due to their negative surface charge; however, the ODTAB-coated, CHX-loaded shellac NPs strongly amplified the antimicrobial action of the CHX for the tested microorganisms. The enhancement of the CHX antimicrobial action was thought to be due to the increased electrostatic adhesion between the cationic surface of the ODTAB-coated, CHX-loaded shellac NPs and the anionic surface of the cell walls of the microorganisms, ensuring direct delivery of CHX with a high concentration locally on the cell membrane. The novel CHX nanocarriers with enhanced antimicrobial action may potentially find applications in dentistry for the development of more efficient formulations against conditions such as gingivitis, periodontitis and other oral infections, as well as enabling formulations to have lower CHX concentrations.
Influence of the Post-Harvest Storage Time on the Multi-Biological Potential, Phenolic and Pyrrolizidine Alkaloid Content of Comfrey (Symphytum officinale L.) Roots Collected from Different European Regions
Authors: Trifan Adriana , Zengin Gokhan , Sinan Kouadio Ibrahime , Esslinger Nils , Grubelnik Andreas , Wolfram Evelyn , Skalicka-Woźniak Krystyna , Minceva Mirjana , Luca Simon Vlad
Published: September 2021

Comfrey (Symphytum officinale L.) roots are well-known bioactive ingredients included in various cosmeceutical and pharmaceutical preparations. In this study, the influence of the post-harvest storage on the chemico-biological potential of roots collected from different European regions and stored for up to six months was investigated. Total phenolic content (TPC) and total phenolic acid content (TPAC) were spectrophotometrically estimated, whereas the levels of individual phenolic and pyrrolizidine alkaloidal markers were determined by HPLC-DAD and HPLC-MS/MS, respectively. The changes in the biological potential was tracked via antioxidant (DPPH, ABTS, CUPRAC, and FRAP) and anti-enzymatic (cholinesterase, tyrosinase, glucosidase, and amylase) assays. TPC and TPAC varied from 6.48–16.57 mg GAE/g d.w. root and from 2.67–9.03 mg CAE/g, respectively. The concentration of the four phenolics (rosmarinic acid, globoidnan A, globoidnan B, rabdosiin) and six pyrrolizidine alkaloids generally showed maximum values at 1–3 months, after which their levels significantly decreased. With respect to the bioassays, the samples showed a wide range of antioxidant and anti-enzymatic effects; however, a direct storage time–bioactivity relationship was not observed. Similar conclusions were also revealed by the multivariate and correlation analyses. Our study could improve the current knowledge of the shelf-life properties of comfrey-based products and enhance their industrial exploitation.
Thermal Stability, Smoke Density, and Flame Retardance of Ecotype Bio-Based Flame Retardant Agricultural Waste Bagasse/Epoxy Composites
Authors: Liu Shang-Hao , Ke Cing-Yu , Chiang Chin-Lung
Published: September 2021

In the study, agricultural waste bagasse was used as a bio-based flame retardant for reducing the flammability of epoxy. Specifically, an interpenetrating network (IPN) was formed through a ring opening reaction between the hydroxyl functional group of bagasse and the epoxy group of triglycidyl isocyanurate (TGIC), forming Bagasse@TGIC. Next, 9, 10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) was mixed with Bagasse@TGIC, inducing a reaction between the active hydrogen of DOPO and the epoxy group of TGIC, ultimately forming Bagasse@TGIC@DOPO with an IPN structure. Finally, the novel flame retardant was added to epoxy to create a composite. The integral procedural decomposition temperature (IPDT) of pure epoxy is 619 °C; after the introduction of the 30 wt% flame retardant, the IPDT of the resultant composite material increased to 799 °C, greatly increasing the thermal stability by 29%. After the addition of the Bagasse@TGIC@DOPO flame retardant, the limiting oxygen index increased from 21% for the pure epoxy to 29% for the composite, and the UL-94 rating improved from failing rating for the pure epoxy and V-0 rating for the composite. The Raman spectrum indicated that the addition of Bagasse@TGIC@DOPO IPN substantially increased the biochar yield during the burning process, increasing thermal stability. These results confirmed that the epoxy/Bagasse@TGIC@DOPO composite had substantial flame retarding effects.
Effect of Ultraviolet Irradiation on Polystyrene Containing Cephalexin Schiff Bases
Authors: Yaseen Anaheed A. , Al-Tikrity Emaad T. B. , Yousif Emad , Ahmed Dina S. , Kariuki Benson M. , El-Hiti Gamal A.
Published: September 2021

The scale of production of polystyrene has escalated in the recent past in order to meet growing demand. As a result, a large quantity of polystyrene waste continues to be generated along with associated health and environmental problems. One way to tackle such problems is to lengthen the lifetime of polystyrene, especially for outdoor applications. Our approach is the synthesis and application of new ultraviolet photostabilizers for polystyrene and this research is focused on four cephalexin Schiff bases. The reaction of cephalexin and 3-hydroxybenzaldehyde, 4-dimethylaminobenzaldehyde, 4-methoxybenzaldehyde, and 4-bromobanzaldehyde under acidic condition afforded the corresponding Schiff bases in high yields. The Schiff bases were characterized and their surfaces were examined. The Schiff bases were mixed with polystyrene to form homogenous blends and their effectiveness as photostabilizers was explored using different methods. The methods included monitoring the changes in the infrared spectra, weight loss, depression in molecular weight, and surface morphology on irradiation. In the presence of the Schiff bases, the formation of carbonyl group fragments, weight loss, and decrease in molecular weight of polystyrene were lower when compared with pure polystyrene. In addition, undesirable changes in the surface such as the appearance of dark spots, cracks, and roughness were minimal for irradiated polystyrene containing cephalexin Schiff bases. Mechanisms by which cephalexin Schiff bases stabilize polystyrene against photodegradation have also been suggested.
Optimization of Process Parameters for Friction Materials Using Multi-Criteria Decision Making: A Comparative Analysis
Authors: Shinde Dinesh , Öktem Hasan , Kalita Kanak , Chakraborty Shankar , Gao Xiao-Zhi
Published: September 2021

Friction materials, mainly made of reinforced composites, should possess excellent physical and tribological properties, such as a higher coefficient of friction, minimum wear, adequate surface hardness, and higher porosity for various automotive brake applications. Attainment of those properties greatly depends on the settings of different input parameters, such as molding pressure, temperature and time, temperature and time of heat treatment/sintering, etc., during the processing of friction materials. In this article, four multi-criteria decision-making (MCDM) tools, i.e., technique for order of preference by similarity to ideal solution (TOPSIS), evaluation based on distance from average solution (EDAS), VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR), and multi-objective optimization on the basis of ratio analysis (MOORA) are applied to identify the optimal parametric combinations for two different friction materials. A comparative analysis of the derived results suggests the same optimal parametric mixes for all the MCDM techniques for both case studies. Thus, for the considered case studies, the optimal parametric combinations as molding time = 8 min, molding temperature = 175 °C, molding pressure = 27 MPa, sintering time = 10 h and sintering temperature = 225 °C, and molding pressure = 27.90 MPa, molding temperature = 170 °C, curing time = 8 min, and heat treatment time = 1 h, respectively, would help in attaining the most desired properties of friction materials. Improvements in the predicted response values prove the efficacy of the adopted MCDM techniques in determining the optimal combinations of various process parameters for friction materials.
DPM Simulations of A-Type FCC Particles’ Fast Fluidization by Use of Structure-Dependent Nonlinear Drag Force
Authors: Wu Guorong , Li Yanggui
Published: September 2021

Nonlinear drag force has been a research frontier in complex gas-solid systems. The literature has reported that the commonly-used drag correlations often overestimate drag force and, thus, cause unrealistic homogeneous flow structures in gas-solid fluidized beds of fine particles. For solving this problem, the structure-dependent drag model, derived from energy-minimization multi-scale approach, is used in discrete simulations of fluid catalytic cracking particles in a small riser. The gas phase is dealt with by computational fluid dynamics. Particles are considered as a discrete phase and described by Newton’s second law of motion. Gas-particle phases are coupled according to Newton’s third law of motion. Simulations show that use of structure-dependent drag model results in drag reduction, the effect of which is not so apparent as that in simulations of the two fluid model. The particle clustering tendency, however, is more distinct and leads to more heterogeneous flow structures in riser flow with a much greater amplitude of outlet solid flux fluctuations. Moreover, the behaviors of particle and gas back-mixing can be captured in the present simulations, which was supported by past simulations and experimental data. The simulation time resolution is discussed. The spring constant can be artificially brought down for safe setting of larger time step when modelling the collision process between fine particles with a higher calculation load. To appropriately mimic the continuous decay of van der Waals force may, however, need a much smaller time step. There is also an obvious effect of space resolution on simulations. When using a grid size smaller than 3 times the particle diameter, the simulated clusters turn extraordinarily large, and the effect of gas-solid back-mixing turns insignificant.
The Tip Clearance Cavitation Mechanism of a High-Speed Centrifugal Pump with a Splitter-Bladed Inducer
Authors: Guo Xiaomei , Yang Shidong , Li Xiaojun , Shi Liang , Hua Ertian , Zhu Zuchao
Published: September 2021

For a high-speed centrifugal pump, cavitation occurs easily. To equip a high-performance splitter-bladed inducer upstream of the pump is an effective method to suppress cavitation. In this paper, an external characteristics experiment of the high-speed centrifugal pump with a splitter-bladed inducer is carried out, and the corresponding numerical calculations are completed. The research shows that the results of the numerical calculation are credible. Numerical cavitation calculations under eight different tip clearance conditions are carried out. First, it is found that the tip clearance (TC) has a certain impact on the head of the centrifugal pump. When TC is in a small range, the clearance leakage is small, and the impact on the head of the pump is not so obvious, which can give the pump a higher performance. Second, it is found that TC has a certain influence on the static pressure distribution in the cascade passage of the splitter-bladed inducer. When TC is in a certain range, the increasement in TC will aggravate the cavitation at the suction surface of the long blades near the inlet. When it exceeds the certain range, it will cause cavitation at the outlet of the inducer. At last, it is found that the cavitation’s severity and position of the inducer are closely related to TC. TC affects the magnitude and position of vorticity in the inducer’s passage. In this paper the flow mechanism of TC is revealed, and its research results can provide theoretical basis and technical support for the design of the tip clearance of the inducers.
How to Tackle Underdeterminacy in Metabolic Flux Analysis? A Tutorial and Critical Review
Authors: Bogaerts Philippe , Vande Wouwer Alain
Published: September 2021

Metabolic flux analysis is often (not to say almost always) faced with system underdeterminacy. Indeed, the linear algebraic system formed by the steady-state mass balance equations around the intracellular metabolites and the equality constraints related to the measurements of extracellular fluxes do not define a unique solution for the distribution of intracellular fluxes, but instead a set of solutions belonging to a convex polytope. Various methods have been proposed to tackle this underdeterminacy, including flux pathway analysis, flux balance analysis, flux variability analysis and sampling. These approaches are reviewed in this article and a toy example supports the discussion with illustrative numerical results.
Ancient Egyptians in Black and White: ‘Exodus: Gods and Kings’ and the Hamitic Hypothesis
Authors: Reed Justin Michael
Published: September 2021

In this essay, I consider how the racial politics of Ridley Scott’s whitewashing of ancient Egypt in Exodus: Gods and Kings intersects with the Hamitic Hypothesis, a racial theory that asserts Black people’s inherent inferiority to other races and that civilization is the unique possession of the White race. First, I outline the historical development of the Hamitic Hypothesis. Then, I highlight instances in which some of the most respected White intellectuals from the late-seventeenth through the mid-twentieth century deploy the hypothesis in assertions that the ancient Egyptians were a race of dark-skinned Caucasians. By focusing on this detail, I demonstrate that prominent White scholars’ arguments in favor of their racial kinship with ancient Egyptians were frequently burdened with the insecure admission that these ancient Egyptian Caucasians sometimes resembled Negroes in certain respects—most frequently noted being skin color. In the concluding section of this essay, I use Scott’s film to point out that the success of the Hamitic Hypothesis in its racial discourse has transformed a racial perception of the ancient Egyptian from a dark-skinned Caucasian into a White person with appearance akin to Northern European White people.