bluuebunny/crossref_metadata_2025 huggingface dataset:
Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System
Authors: Moore Graham J. , Ridgway Harry , Kelaidonis Konstantinos , Chasapis Christos T. , Ligielli Irene , Mavromoustakos Thomas , Bojarska Joanna , Matsoukas John M.
Published: August 2022

Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin ‘antipeptides’. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor ‘switching’ between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans (‘Bisartans’) to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1–7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.
Preparation, Characterization and Permeation Study of Topical Gel Loaded with Transfersomes Containing Asiatic Acid
Authors: Opatha Shakthi Apsara Thejani , Titapiwatanakun Varin , Boonpisutiinant Korawinwich , Chutoprapat Romchat
Published: August 2022

The objective of this study is to investigate the in vitro permeation of asiatic acid (AA) in the form of a topical gel after entrapment in transfersomes by Franz diffusion cells. Transfersomes composed of soybean lecithin and three different edge activators including Tween 80 (TW80), Span 80 (SP80) and sodium deoxycholate (SDC) at the ratio of 50:50, 90:10 and 90:10, respectively, together with 0.3% w/w of AA, were prepared by a high-pressure homogenization technique and further incorporated in gels (TW80AATG, SP80AATG and SDCAATG). All transfersomal gels were characterized for their AA contents, dynamic viscosity, pH and homogeneity. Results revealed that the AA content, dynamic viscosity and pH of the prepared transfersomal gels ranged from 0.272 ± 0.006 to 0.280 ± 0.005% w/w, 812.21 ± 20.22 to 1222.76 ± 131.99 Pa.s and 5.94 ± 0.03 to 7.53 ± 0.03, respectively. TW80AATG gave the highest percentage of AA penetration and flux into the Strat-M® membrane at 8 h (8.53 ± 1.42% and 0.024 ± 0.008 mg/cm2/h, respectively) compared to SP80AATG (8.00 ± 1.70% and 0.019 ± 0.010 mg/cm2/h, respectively), SDCAATG (4.80 ± 0.50% and 0.014 ± 0.004 mg/cm2/h, respectively), non-transfersomal gels (0.73 ± 0.44 to 3.13 ± 0.46% and 0.002 ± 0.001 to 0.010 ± 0.002 mg/cm2/h, respectively) and hydroethanolic AA solution in gel (1.18 ± 0.76% and 0.004 ± 0.003 mg/cm2/h, respectively). These findings indicate that the TW80AATG might serve as a lead formulation for further development toward scar prevention and many types of skin disorders.
Antibody for Serine 65 Phosphorylated Ubiquitin Identifies PLK1-Mediated Phosphorylation of Mitotic Proteins and APC1
Authors: Mann Guy , Sulkshane Prasad , Sadhu Pradeep , Ziv Tamar , Glickman Michael H. , Brik Ashraf
Published: August 2022

Deciphering the protein posttranslational modification (PTM) code is one of the greatest biochemical challenges of our time. Phosphorylation and ubiquitylation are key PTMs that dictate protein function, recognition, sub-cellular localization, stability, turnover and fate. Hence, failures in their regulation leads to various disease. Chemical protein synthesis allows preparation of ubiquitinated and phosphorylated proteins to study their biochemical properties in great detail. However, monitoring these modifications in intact cells or in cell extracts mostly depends on antibodies, which often have off-target binding. Here, we report that the most widely used antibody for ubiquitin (Ub) phosphorylated at serine 65 (pUb) has significant off-targets that appear during mitosis. These off-targets are connected to polo-like kinase 1 (PLK1) mediated phosphorylation of cell cycle-related proteins and the anaphase promoting complex subunit 1 (APC1).
64CuCl2 PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice
Authors: Latgé Adrien , Boisson Frédéric , Ouadi Ali , Averous Gerlinde , Thomas Lionel , Imperiale Alessio , Brasse David
Published: August 2022

64CuCl2 is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of 64CuCl2 in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. 18F-FDG was used as a comparator. Twenty-two animals were imaged 7–9 days following 4T1-cell implantation inside mammary glands. Dynamic 64CuCl2 µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning 18F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor 64CuCl2 accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle 64CuCl2 accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The 18F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. 64CuCl2 PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.
Anti-Pulmonary Fibrosis Activities of Triterpenoids from Oenothera biennis
Authors: Liu Juanjuan , Zhang Jingke , Zeng Mengnan , Li Meng , Xie Shuangshuang , Zheng Xiaoke , Feng Weisheng
Published: August 2022

Five new triterpenoids, oenotheralanosterols C-G (1–5), with seven known triterpenoidcompounds, namely 2α,3α,19α-trihydroxy-24-norurs4,12-dien-28-oic acid (6), 3β,23-dihydroxy-1-oxo-olean-12-en-28-oic acid (7), remangilone C (8), knoxivalic acid A (9), termichebulolide (10), rosasecotriterpene A (11), androsanortriterpene C (12), were extracted and separated from the dichloromethane part of Oenothera biennis L. The anti-pulmonary fibrosis activities of all the compounds against TGF-β1-induced damage tonormal human lung epithelial (BEAS-2B) cells were investigated in vitro. The results showed that compounds 1–2, 6, 8, and 11 exhibited significant anti-pulmonary fibrosis activities, with EC50 values ranging from 4.7 μM to 9.9 μM.
Natural Dietary Compounds in the Treatment of Arsenic Toxicity
Authors: Bjørklund Geir , Rahaman Md. Shiblur , Shanaida Mariia , Lysiuk Roman , Oliynyk Petro , Lenchyk Larysa , Chirumbolo Salvatore , Chasapis Christos T. , Peana Massimiliano
Published: August 2022

Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
Antibiofilm and Anti-Quorum Sensing Potential of Cycloartane-Type Triterpene Acids from Cameroonian Grassland Propolis: Phenolic Profile and Antioxidant Activity of Crude Extract
Authors: Tamfu Alfred Ngenge , Ceylan Ozgur , Cârâc Geta , Talla Emmanuel , Dinica Rodica Mihaela
Published: August 2022

Propolis is very popular for its beneficial health properties, such as antimicrobial activity and antioxidant effects. It is one of the most long-serving traditional medicines to mankind due to its interesting chemical diversity and therapeutic properties. The detailed chemical information of propolis samples is very necessary to guarantee its safety and for it to be accepted into health care systems. The phenolic profile of the hydroethanolic extract was determined using HPLC-DAD, and the antioxidant was evaluated using five complementary methods. Triterpenoids were isolated using column chromatography and characterized using 1H NMR and 13C NMR. The effects of the extract and the isolated compounds on quorum sensing mediated processes and biofilm formation in bacteria were evaluated. Protocatechic acid (40.76 ± 0.82 µg/g), 4-hydroxybenzoic acid (24.04 ± 0.21 µg/g), vanillic acid (29.90 ± 1.05 µg/g), quercetin (43.53 ± 1.10 µg/g), and luteolin (4.44 ± 0.48 µg/g) were identified and quantified. The extract showed good antioxidant activity in the DPPH•, ABTS•+, CUPRAC, and metal chelating assays, and this antioxidant effect was confirmed by cyclic voltammetry. 27-Hydroxymangiferonic acid (1), Ambolic acid (2), and Mangiferonic acid (3) were isolated from anti-quorum sensing activity at MIC, and it was indicated that the most active sample was the extract with inhibition diameter zone of 18.0 ± 1.0 mm, while compounds 1, 2, and 3 had inhibition zones of 12.0 ± 0.5 mm, 9.0 ± 1.0 mm, and 12.3 ± 1.0 mm, respectively. The samples inhibited the P. aeruginosa PA01 swarming motility at the three tested concentrations (50, 75, and 100 μg/mL) in a dose-dependent manner. The propolis extract was able to inhibit biofilm formation by S. aureus, E. coli, P. aeruginosa, C. albicans, and C. tropicalis at MIC concentration. Compound 1 proved biofilm inhibition on S. aureus, L. monocytogenes, E. faecalis, E. coli, and C. tropicalis at MIC and MIC/2; compound 2 inhibited the formation of biofilm at MIC on S. aureus, E. faecalis, E. coli, S. typhi, C. albicans, and C. tropicalis; and compound 3 inhibited biofilm formation on E. faecalis, E. coli, C. albicans, and C. tropicalis and further biofilm inhibition on E. coli at MIC/4 and MIC/8. The studied propolis sample showed important amounts of cycloartane-type triterpene acids, and this indicates that there can be significant intra-regional variation probably due to specific flora within the vicinity. The results indicate that propolis and its compounds can reduce virulence factors of pathogenic bacteria.
Surfactant-Assisted Assembly of Dipeptide Forming a Broom-like Structure
Authors: Wei Yunping , Zhang Jie , Liu Xingcen
Published: August 2022

Understanding the influence of surfactants on the assembly of peptides has a considerable practical motivation. In this paper, we systematically study the anionic surfactant-assisted assembly of diphenylalanine (FF). FF forms broom-like structures in a concentration of sodium cholate (NaC) around the CMC, and assembles into linear and unidirectional rods in the presence of low and high surfactant concentrations. FF’s improved hydrogen bonding and controlled assembly rates are appropriate for other anionic surfactants. At this stage, the use of FF as the simplest protein consequence can be helpful in the investigation of further protein–surfactant interactions.
Atomic-Scale Tracking of Dynamic Nucleation and Growth of an Interfacial Lead Nanodroplet
Authors: Chang Xiaoxue , Sun Chunhao , Ran Leguan , Cai Ran , Shao Ruiwen
Published: August 2022

Revealing the evolutional pathway of the nucleation and crystallization of nanostructures at the atomic scale is crucial for understanding the complex growth mechanisms at the early stage of new substances and spices. Real-time discrimination of the atomic mechanism of a nanodroplet transition is still a formidable challenge. Here, taking advantage of the high temporal and spatial resolution of transmission electron microscopy, the detailed growth pathway of Pb nanodroplets at the early stage of nucleation was directly observed by employing electron beams to induce the nucleation, growth, and fusion process of Pb nanodroplets based on PbTiO3 nanowires. Before the nucleation of Pb nanoparticles, the atoms began to precipitate when they were irradiated by electrons, forming a local crystal structure, and then rapidly and completely crystallized. Small nanodroplets maintain high activity and high density and gradually grow and merge into stable crystals. The whole process was recorded and imaged by HRTEM in real time. The growth of Pb nanodroplets advanced through the classical path and instantaneous droplet coalescence. These results provide an atomic-scale insight on the dynamic process of solid/solid interface, which has implications in thin-film growth and advanced nanomanufacturing.
Effects of Different Denaturants on the Properties of a Hot-Pressed Peanut Meal-Based Adhesive
Authors: Qu Yang , Guo Qin , Li Tian , Liu Hongzhi , Wang Qiang
Published: August 2022

Plant protein-based adhesives could fundamentally solve the problem of formaldehyde-based adhesive releasing formaldehyde, but enhancing bonding strength and water resistance is a necessary measure to realize practical applications. In this study, the effects of different denaturants on the properties of a hot-pressed peanut meal (HPM)-based adhesive before and after crosslinking were studied. Papain, sodium dodecyl sulfate (SDS), urea and crosslinker-polyamide epichlorohydrin (PAE) were used to prepare HPM-based adhesives. The functional groups, bonding strength, thermal behaviors, mass loss, moisture uptake value, viscosity and fracture surface of adhesive samples were analyzed. As a result, (1) papain was used to break HPM protein (HPMP) into polypeptide chains and to reduce the water resistance. (2) SDS and urea unfold the HPMP molecule and expose internal hydrophobic groups to improve the water resistance of the adhesive. (3) A denser network structure was formed by PAE and HPMP molecules, which significantly improved the bonding strength and water resistance of adhesives. In particular, after SDS denaturation and PAE crosslinking, compared with pure HPM adhesive, the wet shear strength increased by 96.4%, the mass loss and moisture uptake value reduced by 41.4% and 69.4%, and viscosity increased by 30.4%. This work provided an essential guide to design and prepare HPM-based adhesives.
The Derived Components of Gnaphalium hypoleucum DC. Reduce Quorum Sensing of Chromobacterium violaceum
Authors: Li Yu-Long , Chu Zi-Yong , Liu Gui-Min , Yang Sheng-Qiang , Zeng Hong
Published: August 2022

Gnaphalium hypoleucum DC. was first recorded in the Chinese National Pharmacopoeia “Yi Plant Medicine”. There is no detailed report on its main components’ activity in suppressing the quorum sensing activity (QS) of bacteria. Our study aimed to screen the main components in extracts of G. hypoleucum DC. in order to measure their effects on bacterial QS activity and to explore specific quorum sensing mechanisms that are affected by G. hypoleucum DC. extracts. Crude extracts of G. hypoleucum DC. contained significant amounts of two compounds shown to inhibit bacterial QS activity, namely apigenin and luteolin. Apigenin and luteolin in crude extracts of G. hypoleucum DC. showed substantial inhibition of pigment formation, biofilm production, and motility in Chromobacterium violaceum ATCC 12472 compared to the effects of other phytochemicals from G. hypoleucum DC. Apigenin and luteolin exhibited a strong QS inhibitory effect on C. violaceum, interfering with the violacein pigment biosynthesis by downregulating the vioB, vioC, and vioD genes. In the presence of signal molecules, the QS effect is prevented, and the selected compounds can still inhibit the production of the characteristic purple pigment in C. violaceum. Based on qualitative and quantitative research using genomics and bioinformatics, we concluded that apigenin and luteolin in crude extracts of G. hypoleucum DC can interfere with the generation of QS in C. violaceum by downregulating the vioB, vioC, and vioD genes. Indeed, G. hypoleucum DC. is used for the treatment of bacterial infections, and this research provides new ideas and potential alternative uses for medicinal plants.
Correlating Sensory Assessment of Smoke-Tainted Wines with Inter-Laboratory Study Consensus Values for Volatile Phenols
Authors: Favell James W. , Wilkinson Kerry L. , Zigg Ieva , Lyons Sarah M. , Ristic Renata , Puglisi Carolyn J. , Wilkes Eric , Taylor Randell , Kelly Duane , Howell Greg , McKay Marianne , Mokwena Lucky , Plozza Tim , Zhang Pei , Bui AnhDuyen , Porter Ian , Frederick Orrin , Karasek Jasha , Szeto Colleen , Pan Bruce S. , Tallman Steve , McClure Beth Anne , Feng Hui , Hervé Eric , Oberholster Anita , Zandberg Wesley F. , Noestheden Matthew
Published: August 2022

Vineyard exposure to wildfire smoke can taint grapes and wine. To understand the impact of this taint, it is imperative that the analytical methods used are accurate and precise. This study compared the variance across nine commercial and research laboratories following quantitative analysis of the same set of smoke-tainted wines. In parallel, correlations between the interlaboratory consensus values for smoke-taint markers and sensory analyses of the same smoke-tainted wines were evaluated. For free guaiacol, the mean accuracy was 94 ± 11% in model wine, while the free cresols and 4-methylguaiacol showed a negative bias and/or decreased precision relative to guaiacol. Similar trends were observed in smoke-tainted wines, with the cresols and glycosidically bound markers demonstrating high variance. Collectively, the interlaboratory results show that data from a single laboratory can be used quantitatively to understand smoke-taint. Results from different laboratories, however, should not be directly compared due to the high variance between study participants. Correlations between consensus compositional data and sensory evaluations suggest the risk of perceivable smoke-taint can be predicted from free cresol concentrations, overcoming limitations associated with the occurrence of some volatile phenols, guaiacol in particular, as natural constituents of some grape cultivars and of the oak used for barrel maturation.
Predicting the Surface Tension of Deep Eutectic Solvents: A Step Forward in the Use of Greener Solvents
Authors: Halder Amit Kumar , Haghbakhsh Reza , Voroshylova Iuliia V. , Duarte Ana Rita C. , Cordeiro Maria Natalia D. S.
Published: August 2022

Deep eutectic solvents (DES) are an important class of green solvents that have been developed as an alternative to toxic solvents. However, the large-scale industrial application of DESs requires fine-tuning their physicochemical properties. Among others, surface tension is one of such properties that have to be considered while designing novel DESs. In this work, we present the results of a detailed evaluation of Quantitative Structure-Property Relationships (QSPR) modeling efforts designed to predict the surface tension of DESs, following the Organization for Economic Co-operation and Development (OECD) guidelines. The data set used comprises a large number of structurally diverse binary DESs and the models were built systematically through rigorous validation methods, including ‘mixtures-out’- and ‘compounds-out’-based data splitting. The most predictive individual QSPR model found is shown to be statistically robust, besides providing valuable information about the structural and physicochemical features responsible for the surface tension of DESs. Furthermore, the intelligent consensus prediction strategy applied to multiple predictive models led to consensus models with similar statistical robustness to the individual QSPR model. The benefits of the present work stand out also from its reproducibility since it relies on fully specified computational procedures and on publicly available tools. Finally, our results not only guide the future design and screening of novel DESs with a desirable surface tension but also lays out strategies for efficiently setting up silico-based models for binary mixtures.
Neutrophil Immunomodulatory Activity of (−)-Borneol, a Major Component of Essential Oils Extracted from Grindelia squarrosa
Authors: Schepetkin Igor A. , Özek Gulmira , Özek Temel , Kirpotina Liliya N. , Khlebnikov Andrei I. , Quinn Mark T.
Published: August 2022

Grindelia squarrosa (Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEOFl) and leaves (GEOLv) of G. squarrosa and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.7 and 23.2% in GEOFl and GEOLv, respectively), limonene (10.0 and 14.7%), borneol (23.4 and 16.6%), p-cymen-8-ol (6.1 and 5.8%), β-pinene (4.0 and 3.8%), bornyl acetate (3.0 and 5.1%), trans-pinocarveol (4.2 and 3.7%), spathulenol (3.0 and 2.0%), myrtenol (2.5 and 1.7%), and terpinolene (1.7 and 2.0%). Enantiomer analysis showed that α-pinene, β-pinene, and borneol were present primarily as (−)-enantiomers (100% enantiomeric excess (ee) for (−)-α-pinene and (−)-borneol in both GEOFl and GEOLv; 82 and 78% ee for (−)-β-pinene in GEOFl and GEOLv), while limonene was present primarily as the (+)-enantiomer (94 and 96 ee in GEOFl and GEOLv). Grindelia essential oils activated human neutrophils, resulting in increased [Ca2+]i (EC50 = 22.3 µg/mL for GEOFl and 19.4 µg/mL for GEOLv). In addition, one of the major enantiomeric components, (−)-borneol, activated human neutrophil [Ca2+]i (EC50 = 28.7 ± 2.6), whereas (+)-borneol was inactive. Since these treatments activated neutrophils, we also evaluated if they were able to down-regulate neutrophil responses to subsequent agonist activation and found that treatment with Grindelia essential oils inhibited activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, (−)-borneol inhibited FPR-agonist-induced Ca2+ influx in neutrophils. Grindelia leaf and flower essential oils, as well as (−)-borneol, also inhibited fMLF-induced chemotaxis of human neutrophils (IC50 = 4.1 ± 0.8 µg/mL, 5.0 ± 1.6 µg/mL, and 5.8 ± 1.4 µM, respectively). Thus, we identified (−)-borneol as a novel modulator of human neutrophil function.
Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice
Authors: Rmandić Milena , Stajić Ana , Jančić Jasna , Samardžić Janko , Jović Nebojša , Malenović Anđelija
Published: August 2022

In this research, a UHPLC–MS/MS method was developed and validated for the determination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 µm particle size) column with mobile phase comprising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min, the column temperature was 30 °C and the injection volume was 3 µL. Desolvation temperature, desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS areas were determined by the image processing tool. The influence of hematocrit values (20–60%) on accuracy and precision was evaluated to determine the range within which method for DBSs is free from Hct or dependency is within acceptable limits. The validated method was applied to the determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was estimated by correlating its DPS and DBS levels.
Thiocoumarins: From the Synthesis to the Biological Applications
Authors: Matos Maria J. , Santana Lourdes , Uriarte Eugenio , Borges Fernanda
Published: August 2022

Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.
Physical Properties and Prebiotic Activities (Lactobacillus spp.) of Gelatine-Based Gels Formulated with Agave Fructans and Agave Syrups as Sucrose and Glucose Substitutes
Authors: Rodríguez-Rodríguez Rogelio , Barajas-Álvarez Paloma , Morales-Hernández Norma , Camacho-Ruíz Rosa María , Espinosa-Andrews Hugo
Published: August 2022

This research developed model foods of gelatine-based gels, where carbohydrates from Agave tequilana Weber var. Azul (agave syrups or/and agave fructans) were incorporated into gel formulations as healthy sucrose and glucose substitutes. The sugars (sucrose and glucose) were substituted by agave carbohydrates (agave syrups and agave fructans), obtaining the subsequent gel formulations: 100% agave syrup (F2 gel), 100% agave fructan (F3 gel), and 50% agave syrup–50% agave fructan (F4 gel). The unsubstituted gel formulation was used as a control (F1 gel). The prebiotic activities, physical properties, thermal stability (HP-TLC), and texture of gelatine-based gels were evaluated. The gel formulations showed translucent appearances with approximately 36 g/100 g of water and water activities values between 0.823 and 0.929. The HP-TLC analysis validated that agave fructans did not hydrolyse during the thermal process of gels production. Gels produced with agave syrup and agave fructan (F2-F4 gels) provided higher hardness, gumminess, and springiness values (p < 0.05) than those produced with glucose and sucrose (F1 gel). Gelatine-based gel formulations displayed prebiotic activities correlated to the ability of Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus rhamnosus to use agave carbohydrates as carbon sources. Based on the prebiotic effect and physical and textural properties, the F2 and F4 gel formulations displayed the best techno-functional properties to produce gel soft candies.
Decoration of A-Ring of a Lupane-Type Triterpenoid with Different Oxygen and Nitrogen Heterocycles
Authors: Sousa Joana L. C. , Albuquerque Hélio M. T. , Silvestre Armando J. D. , Silva Artur M. S.
Published: August 2022

Betulinic acid (BA) was used as starting building block to create a library of novel BA-derived compounds containing O- and N-heterocycles. Firstly, BA was converted into methyl betulonate (BoOMe), which was used as intermediate in the developed methodologies. 1,2-Oxazine-fused BoOMe compounds were obtained in 12–25% global yields through a Michael addition of nitromethane to methyl (E)-2-benzylidenebetulonate derivatives, followed by nitro group reduction and intramolecular cyclization. Remarkably, the triterpene acts as a diastereoselective inducer in the conjugate addition of nitromethane, originating only one diastereomer out of four possible ones. Furthermore, other oxygen and nitrogen-containing heterocycles were installed at the A-ring of BoOMe, affording 2-amino-3-cyano-4H-pyran-fused BoOMe, diarylpyridine-fused BoOMe and 1,2,3-triazole–BoOMe compounds, using simple and straightforward synthetic methodologies. Finally, BA was revealed to be a versatile starting material, allowing the creation of a molecular diversification of compounds containing a triterpenic scaffold and O- and N-heterocycles.
On the Morphology of Nanostructured TiO2 for Energy Applications: The Shape of the Ubiquitous Nanomaterial
Authors: Gagliardi Serena , Rondino Flaminia , Paoletti Claudia , Falconieri Mauro
Published: August 2022

Nanostructured titania is one of the most commonly encountered constituents of nanotechnology devices for use in energy-related applications, due to its intrinsic functional properties as a semiconductor and to other favorable characteristics such as ease of production, low toxicity and chemical stability, among others. Notwithstanding this diffusion, the quest for improved understanding of the physical and chemical mechanisms governing the material properties and thus its performance in devices is still active, as testified by the large number of dedicated papers that continue to be published. In this framework, we consider and analyze here the effects of the material morphology and structure in determining the energy transport phenomena as cross-cutting properties in some of the most important nanophase titania applications in the energy field, namely photovoltaic conversion, hydrogen generation by photoelectrochemical water splitting and thermal management by nanofluids. For these applications, charge transport, light transport (or propagation) and thermal transport are limiting factors for the attainable performances, whose dependence on the material structural properties is reviewed here on its own. This work aims to fill the gap existing among the many studies dealing with the separate applications in the hope of stimulating novel cross-fertilization approaches in this research field.
DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles
Authors: Chen Zhangjian , Shi Jiaqi , Zhang Yi , Han Shuo , Zhang Jiahe , Jia Guang
Published: August 2022

The genotoxicity of nanomaterials has attracted great attention in recent years. As a possible occupational carcinogen, the genotoxic effects and underlying mechanisms of titanium dioxide nanoparticles (TiO2 NPs) have been of particular concern. In this study, the effect of TiO2 NPs (0, 25, 50 and 100 µg/mL) on DNA damage and the role of oxidative stress were investigated using human bronchial epithelial cells (BEAS-2B) as an in vitro model. After detailed characterization, the cytotoxicity of TiO2 NPs was detected. Through transmission electron microscopy (TEM), we found that TiO2 NPs entered the cytoplasm but did not penetrate deep into the nucleus of cells. The intracellular levels of reactive oxygen species (ROS) significantly increased in a dose-dependent manner and the ratios of GSH/GSSG also significantly decreased. The results of the normal comet assay were negative, while the Fpg-modified comet assay that specifically detected DNA oxidative damage was positive. Meanwhile, N-acetyl-L-cysteine (NAC) intervention inhibited the oxidative stress and genotoxicity induced by TiO2 NPs. Therefore, it was suggested that TiO2 NPs could induce cytotoxicity, oxidative stress and DNA oxidative damage in BEAS-2B cells. DNA oxidative damage may be a more sensitive genetic endpoint to detect the genotoxicity of TiO2 NPs.
Recent Advances Regarding Precious Metal-Based Electrocatalysts for Acidic Water Splitting
Authors: Peng Yuanting , Liao Yucong , Ye Donghao , Meng Zihan , Wang Rui , Zhao Shengqiu , Tian Tian , Tang Haolin
Published: August 2022

Electrochemical water splitting has wide applicability in preparing high-density green energy. The Proton exchange membrane (PEM) water electrolysis system is a promising technique for the generation of hydrogen due to its high electrolytic efficiency, safety and reliability, compactness, and quick response to renewable energy sources. However, the instability of catalysts for electrochemical water splitting under operating conditions limits their practical applications. Until now, only precious metal-based materials have met the requirements for rigorous long-term stability and high catalytic activity under acid conditions. In this review, the recent progress made in this regard is presented and analyzed to clarify the role of precious metals in the promotion of the electrolytic decomposition of water. Reducing precious metal loading, enhancing catalytic activity, and improving catalytic lifetime are crucial directions for developing a new generation of PEM water electrolysis catalysts. A summary of the synthesis of high-performance catalysts based on precious metals and an analysis of the factors affecting catalytic performance were derived from a recent investigation. Finally, we present the remaining challenges and future perspectives as guidelines for practical use.
Palladium Nanoparticles Synthesized by Laser Ablation in Liquids for Antimicrobial Applications
Authors: Fernández-Arias Mónica , Vilas Ana M. , Boutinguiza Mohamed , Rodríguez Daniel , Arias-González Felipe , Pou-Álvarez Pablo , Riveiro Antonio , Gil Javier , Pou Juan
Published: August 2022

Antibiotic resistance is a leading cause of death worldwide. In this paper, we explore new alternatives in the treatment of infections. Noble metal nanoparticles could help to mitigate this problem. In this work, palladium nanoparticles were synthesized by laser ablation in order to explore their antimicrobial capacity. To obtain palladium nanoparticles, a palladium plate immersed in water, or methanol, was ablated, using two pulsed lasers that emit radiation with wavelengths of 532 nm and 1064 nm, respectively. Pure Pd-NPs with crystalline microstructure and rounded shape were obtained. The nanoparticles’ size is more homogeneous if the laser wavelength is 532 nm, and it decreases when methanol is used as solvent, reaching mean diameters smaller than 6 nm. With the objective of studying antimicrobial activity against Staphylococcus aureus, the Pd-NPs were immobilized on the surface of titanium discs. The release of palladium ions was recorded during the first seven days, and the cytotoxicity of the immobilized NPs was also tested with L929 mouse fibroblast cell line. Palladium nanoparticles synthesized by means of the infrared laser in methanol showed a strong inhibitory effect on S. aureus and good cytocompatibility, with no toxic effect on fibroblast cells.
Effect of Nanoencapsulation on the Antimicrobial and Antibiofilm Activities of Algerian Origanum glandulosum Desf. against Multidrug-Resistant Clinical Isolates
Authors: Bouaouina Sarah , Aouf Abdelhakim , Touati Abdelaziz , Ali Hatem , Elkhadragy Manal , Yehia Hany , Farouk Amr
Published: August 2022

The emergence of multidrug-resistant (MDR) bacteria is a danger to public health and exposes patients to high risk, increasing morbidity and mortality worldwide. For this purpose, three months of evaluation of MDR’s prevalence and antimicrobial susceptibility patterns in the military regional university hospital of Constantine from different services and samples was carried out. Among a total of 196 isolates, 35.2% were MDR. The use of essential oils such as Origanum glandulosum Desf. as an alternative to antibiotics is attractive due to their rich content of bioactive compounds conferring many biological activities. Also, to overcome the drawbacks of using oils as the hydrophobicity and negative interaction with the environmental conditions, in addition to increasing their activity, encapsulation for the oil was performed using high-speed homogenization (HSH) into nanocapsules and high-pressure homogenization (HPH) into nanoemulsion. Nine volatile constituents were determined using gas chromatography-mass spectrometry analysis (GC-MS) in hydrodistilled oil with thymol, carvacrol, p-cymene, and γ-terpinene as dominants. A dramatic decrease in the major volatile components was observed due to the use of HSH and HPH but generated the same oil profile. The mean particle size of the nanoemulsion was 54.24 nm, while that of nanocapsules was 120.60 nm. The antibacterial activity of the oil and its nanoparticles was estimated on MDR isolates using the disk diffusion, aromatogram, and broth microdilution methods. Consistent with the differences in volatile constituents, the oil exhibited a higher antibacterial activity compared to its nanoforms with the diameters of the inhibition zone against E. coli (20 mm), S. aureus (35 mm), and A. baumannii (40 mm). Both formulations have shown relatively significant activity against the biofilm state at sub-inhibitory concentrations, where nanoemulsion was more potent than nanocapsules. The results obtained suggested that nanoformulations of essential oils are strongly recommended for therapeutic application as alternatives to antibiotics.
COVID-19 Detection via Silicon Nanowire Field-Effect Transistor: Setup and Modeling of Its Function
Authors: Wasfi Asma , Awwad Falah , Gelovani Juri George , Qamhieh Naser , Ayesh Ahmad I.
Published: August 2022

Biomolecular detection methods have evolved from simple chemical processes to laboratory sensors capable of acquiring accurate measurements of various biological components. Recently, silicon nanowire field-effect transistors (SiNW-FETs) have been drawing enormous interest due to their potential in the biomolecular sensing field. SiNW-FETs exhibit capabilities such as providing real-time, label-free, highly selective, and sensitive detection. It is highly critical to diagnose infectious diseases accurately to reduce the illness and death spread rate. In this work, a novel SiNW-FET sensor is designed using a semiempirical approach, and the electronic transport properties are studied to detect the COVID-19 spike protein. Various electronic transport properties such as transmission spectrum, conductance, and electronic current are investigated by a semiempirical modeling that is combined with a nonequilibrium Green’s function. Moreover, the developed sensor selectivity is tested by studying the electronic transport properties for other viruses including influenza, rotavirus, and HIV. The results indicate that SiNW-FET can be utilized for accurate COVID-19 identification with high sensitivity and selectivity.
Interferon Epsilon Signaling Confers Attenuated Zika Replication in Human Vaginal Epithelial Cells
Authors: Mungin James W. , Chen Xin , Liu Bindong
Published: August 2022

Zika virus (ZIKV) is an emerging flavivirus that causes congenital birth defects and neurological compilations in the human host. Although ZIKV is primarily transmitted through infected mosquitos, recent studies reveal sexual contact as a potential transmission route. In vagina-bearing individuals, the vaginal epithelium constitutes the first line of defense against viruses. However, it is unclear how ZIKV interacts with the vaginal epithelium to initiate ZIKV transmission. In this study, we demonstrate that exposing ZIKV to human vaginal epithelial cells (hVECs) resulted in de novo viral RNA replication, increased envelope viral protein production, and a steady, extracellular release of infectious viral particles. Interestingly, our data show that, despite an increase in viral load, the hVECs did not exhibit significant cytopathology in culture as other cell types typically do. Furthermore, our data reveal that the innate antiviral state of hVECs plays a crucial role in preventing viral cytopathology. For the first time, our data show that interferon epsilon inhibits ZIKV replication. Collectively, our results in this study provide a novel perspective on the viral susceptibility and replication dynamics during ZIKV infection in the human vaginal epithelium. These findings will be instrumental towards developing therapeutic agents aimed at eliminating the pathology caused by the virus.
Characterization of Host-Specific Genes from Pine- and Grass-Associated Species of the Fusarium fujikuroi Species Complex
Authors: Dewing Claudette , Van der Nest Magrieta A. , Santana Quentin C. , Proctor Robert H. , Wingfield Brenda D. , Steenkamp Emma T. , De Vos Lieschen
Published: August 2022

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease for numerous crops and synthesize a variety of secondary metabolites that can contaminate feedstocks and food. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport through to virulence/pathogenicity. Most genes arose early during the evolution of Fusarium/FFSC and were only subsequently retained in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in the grass- and pine-associated FFSC taxa examined. It also highlighted the diversity of the molecular processes potentially underlying niche-specificity in these and other Fusarium species.
LC3-Associated Phagocytosis in Bacterial Infection
Authors: Yuan Jin , Zhang Qiuyu , Chen Shihua , Yan Min , Yue Lei
Published: August 2022

LC3-associated phagocytosis (LAP) is a noncanonical autophagy process reported in recent years and is one of the effective mechanisms of host defense against bacterial infection. During LAP, bacteria are recognized by pattern recognition receptors (PRRs), enter the body, and then recruit LC3 onto a single-membrane phagosome to form a LAPosome. LC3 conjugation can promote the fusion of the LAPosomes with lysosomes, resulting in their maturation into phagolysosomes, which can effectively kill the identified pathogens. However, to survive in host cells, bacteria have also evolved strategies to evade killing by LAP. In this review, we summarized the mechanism of LAP in resistance to bacterial infection and the ways in which bacteria escape LAP. We aim to provide new clues for developing novel therapeutic strategies for bacterial infectious diseases.
Histopathological Features of SARS-CoV-2 in Extrapulmonary Organ Infection: A Systematic Review of Literature
Authors: Torge Diana , Bernardi Sara , Arcangeli Mauro , Bianchi Serena
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern responsible for the ongoing pandemic. Histopathological pieces of evidence on COVID-19 are not fully investigated. This review aims to provide, through microscopy investigations, a histopathological overview of COVID-19 structural and ultrastructural alterations in different organs and tissues, excluding the respiratory system. The authors systematically reviewed the literature over the period February 2020–July 2022. Selected databases were PubMed, Scopus, and Google Scholar. The search strategy included the following terms: “COVID-19” or SARS-CoV-2 and “histopathology” or “pathology”; and “microscopy” and “liver”, “myocardium”,” spleen”, “testis”, and “placenta”. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Thirty-one articles included in this systematic review demonstrated, at a histopathological level, that COVID-19 exerts detrimental effects on tissues, often promoting degenerative processes. Even if COVID-19 shows a histopathological tropism for the respiratory system, other tissues, from cardiovascular to reproductive, are affected by COVID-19. Therefore, this paper provides an up-to-date view of histopathological observations of the structural and ultrastructural alterations associated with COVID-19 and may contribute to a better knowledge of the physiopathological bases of this disease.
Progress in 3D Bioprinting Technology for Osteochondral Regeneration
Authors: Lafuente-Merchan Markel , Ruiz-Alonso Sandra , García-Villén Fátima , Gallego Idoia , Gálvez-Martín Patricia , Saenz-del-Burgo Laura , Pedraz Jose Luis
Published: August 2022

Osteochondral injuries can lead to osteoarthritis (OA). OA is characterized by the progressive degradation of the cartilage tissue together with bone tissue turnover. Consequently, joint pain, inflammation, and stiffness are common, with joint immobility and dysfunction being the most severe symptoms. The increase in the age of the population, along with the increase in risk factors such as obesity, has led OA to the forefront of disabling diseases. In addition, it not only has an increasing prevalence, but is also an economic burden for health systems. Current treatments are focused on relieving pain and inflammation, but they become ineffective as the disease progresses. Therefore, new therapeutic approaches, such as tissue engineering and 3D bioprinting, have emerged. In this review, the advantages of using 3D bioprinting techniques for osteochondral regeneration are described. Furthermore, the biomaterials, cell types, and active molecules that are commonly used for these purposes are indicated. Finally, the most recent promising results for the regeneration of cartilage, bone, and/or the osteochondral unit through 3D bioprinting technologies are considered, as this could be a feasible therapeutic approach to the treatment of OA.
Implementation of a New Electronic Liquid Dispensing System for Individualized Compounding of Hard Capsules
Authors: Sarker Bakul , Fligge Mariele , Knaab Tanja , Breitkreutz Jörg
Published: August 2022

An automated compounding device can be a useful tool for the rapid and accurate production of small batches for personalized medicine as well as for clinical batches. A novel electronic liquid dispensing system (ELDS) was investigated to produce hard capsules with individualized dose strengths. An ethanol-based solvent system containing the antihypertensive enalapril maleate was extruded through a cannula into prefilled capsules. The capsules were prefilled with a powder bed of mesoporous silica (Syloid 244 FP) or synthetic dibasic calcium phosphate anhydrous (Fujicalin). The dosing accuracy as well as content uniformity of ELDS was compared with manual preparation using a Hamilton syringe (HS). Both methods met the pharmacopeia criteria for all formulations with an acceptance value (AV) less than 15. Drug adherence to the capsule shells was also investigated. A recovery rate of 98% of enalapril maleate showed almost no drug loss, but the appropriateness of the new dispensing method.