bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the Anticancer Mechanisms of Traditional Herbal Medicines with Metabolomics
Authors: Oyenihi Omolola R. , Oyenihi Ayodeji B. , Erhabor Joseph O. , Matsabisa Motlalepula G. , Oguntibeju Oluwafemi O.
Published: November 2021

Metabolite profiling of cancer cells presents many opportunities for anticancer drug discovery. The Chinese, Indian, and African flora, in particular, offers a diverse source of anticancer therapeutics as documented in traditional folklores. In-depth scientific information relating to mechanisms of action, quality control, and safety profile will promote their extensive usage in cancer therapy. Metabolomics may be a more holistic strategy to gain valuable insights into the anticancer mechanisms of action of plants but this has remained largely unexplored. This review, therefore, presents the available metabolomics studies on the anticancer effects of herbal medicines commonly used in Africa and Asia. In addition, we present some scientifically understudied ‘candidate plants’ for cancer metabolomics studies and highlight the relevance of metabolomics in addressing other challenges facing the drug development of anticancer herbs. Finally, we discussed the challenges of using metabolomics to uncover the underlying mechanisms of potential anticancer herbs and the progress made in this regard.
Type-3 Hyaluronan Synthase Attenuates Tumor Cells Invasion in Human Mammary Parenchymal Tissues
Authors: Lee Wen-Jui , Tu Shih-Hsin , Cheng Tzu-Chun , Lin Juo-Han , Sheu Ming-Thau , Kuo Ching-Chuan , Changou Chun A. , Wu Chih-Hsiung , Chang Hui-Wen , Chang Hang-Lung , Chen Li-Ching , Ho Yuan-Soon
Published: November 2021

The microenvironment for tumor growth and developing metastasis should be essential. This study demonstrated that the hyaluronic acid synthase 3 (HAS3) protein and its enzymatic product hyaluronic acid (HA) encompassed in the subcutaneous extracellular matrix can attenuate the invasion of human breast tumor cells. Decreased HA levels in subcutaneous Has3-KO mouse tissues promoted orthotopic breast cancer (E0771) cell-derived allograft tumor growth. MDA-MB-231 cells premixed with higher concentration HA attenuate tumor growth in xenografted nude mice. Human patient-derived xenotransplantation (PDX) experiments found that HA selected the highly migratory breast cancer cells with CD44 expression accumulated in the tumor/stroma junction. In conclusion, HAS3 and HA were detected in the stroma breast tissues at a high level attenuates effects for induced breast cancer cell death, and inhibit the cancer cells invasion at the initial stage. However, the highly migratory cancer cells were resistant to the HA-mediated effects with unknown mechanisms.
Chemical Analysis and In Vitro Bioactivity of Essential Oil of Laurelia sempervirens and Safrole Derivatives against Oomycete Fish Pathogens
Authors: Madrid Alejandro , Morales Ana Lizeth , Saffirio Valentina , Cuellar Mauricio A. , Werner Enrique , Said Bastián , Godoy Patricio , Caro Nelson , Melo Mirna , Montenegro Iván
Published: November 2021

In this study, the essential oil (EO) from Laurelia sempervirens was analyzed by GC/MS and safrole (1) was identified as the major metabolite 1, was subjected to direct reactions on the oxygenated groups in the aromatic ring and in the side chain, and eight compounds (4 to 12) were obtained by the process. EO and compounds 4–12 were subjected to biological assays on 24 strains of the genus Saprolegnia, specifically of the species 12 S. parasitica and 12 S. australis. EO showed a significant effect against Saprolegnia strains. Compound 6 presents the highest activity against two resistant strains, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 25 to 100 and 75 to 125 µg/mL, respectively. The results show that compound 6 exhibited superior activities compared to the commercial controls bronopol and azoxystrobin used to combat these pathogens.
Antibacterial Activity of Thymus vulgaris L. Essential Oil Vapours and Their GC/MS Analysis Using Solid-Phase Microextraction and Syringe Headspace Sampling Techniques
Authors: Antih Julien , Houdkova Marketa , Urbanova Klara , Kokoska Ladislav
Published: November 2021

While the inhalation of Thymus vulgaris L. essential oil (EO) is commonly approved for the treatment of mild respiratory infections, there is still a lack of data regarding the antimicrobial activity and chemical composition of its vapours. The antibacterial activity of the three T. vulgaris EOs against respiratory pathogens, including Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pyogenes, was assessed in both liquid and vapour phases using the broth microdilution volatilisation (BMV) method. With the aim of optimising a protocol for the characterisation of EO vapours, their chemical profiles were determined using two headspace sampling techniques coupled with GC/MS: solid-phase microextraction (HS-SPME) and syringe headspace sampling technique (HS-GTS). All EO sample vapours exhibited antibacterial activity with minimum inhibitory concentrations (MIC) ranging from 512 to 1024 μg/mL. According to the sampling technique used, results showed a different distribution of volatile compounds. Notably, thymol was found in lower amounts in the headspace—peak percentage areas below 5.27% (HS-SPME) and 0.60% (HS-GTS)—than in EOs (max. 48.65%), suggesting that its antimicrobial effect is higher in vapour. Furthermore, both headspace sampling techniques were proved to be complementary for the analysis of EO vapours, whereas HS-SPME yielded more accurate qualitative results and HS-GTS proved a better technique for quantitative analysis.
Effect of Tetraphenylborate on Physicochemical Properties of Bovine Serum Albumin
Authors: Grabowska Ola , Kogut Małgorzata M. , Żamojć Krzysztof , Samsonov Sergey A. , Makowska Joanna , Tesmar Aleksandra , Chmur Katarzyna , Wyrzykowski Dariusz , Chmurzyński Lech
Published: November 2021

The binding interactions of bovine serum albumin (BSA) with tetraphenylborate ions ([B(Ph)4]−) have been investigated by a set of experimental methods (isothermal titration calorimetry, steady-state fluorescence spectroscopy, differential scanning calorimetry and circular dichroism spectroscopy) and molecular dynamics-based computational approaches. Two sets of structurally distinctive binding sites in BSA were found under the experimental conditions (10 mM cacodylate buffer, pH 7, 298.15 K). The obtained results, supported by the competitive interactions experiments of SDS with [B(Ph)4]− for BSA, enabled us to find the potential binding sites in BSA. The first site is located in the subdomain I A of the protein and binds two [B(Ph)4]− ions (logK(ITC)1 = 7.09 ± 0.10; ΔG(ITC)1 = −9.67 ± 0.14 kcal mol−1; ΔH(ITC)1 = −3.14 ± 0.12 kcal mol−1; TΔS(ITC)1 = −6.53 kcal mol−1), whereas the second site is localized in the subdomain III A and binds five ions (logK(ITC)2 = 5.39 ± 0.06; ΔG(ITC)2 = −7.35 ± 0.09 kcal mol−1; ΔH(ITC)2 = 4.00 ± 0.14 kcal mol−1; TΔS(ITC)2 = 11.3 kcal mol−1). The formation of the {[B(Ph)4]−}–BSA complex results in an increase in the thermal stability of the alfa-helical content, correlating with the saturation of the particular BSA binding sites, thus hindering its thermal unfolding.
Critical Review of Synthesis, Toxicology and Detection of Acyclovir
Authors: Wei Yan-Ping , Yao Liang-Yuan , Wu Yi-Yong , Liu Xia , Peng Li-Hong , Tian Ya-Ling , Ding Jian-Hua , Li Kang-Hua , He Quan-Guo
Published: November 2021

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV’s ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection–chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.
Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis
Authors: Behl Tapan , Upadhyay Tanuj , Singh Sukhbir , Chigurupati Sridevi , Alsubayiel Amal M. , Mani Vasudevan , Vargas-De-La-Cruz Celia , Uivarosan Diana , Bustea Cristiana , Sava Cristian , Stoicescu Manuela , Radu Andrei-Flavius , Bungau Simona Gabriela
Published: November 2021

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.
Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
Authors: Pearson Russell , Butler Anthony
Published: November 2021

Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN’s bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.
Modulating Glycoside Hydrolase Activity between Hydrolysis and Transfer Reactions Using an Evolutionary Approach
Authors: Arreola-Barroso Rodrigo A. , Llopiz Alexey , Olvera Leticia , Saab-Rincón Gloria
Published: November 2021

The proteins within the CAZy glycoside hydrolase family GH13 catalyze the hydrolysis of polysaccharides such as glycogen and starch. Many of these enzymes also perform transglycosylation in various degrees, ranging from secondary to predominant reactions. Identifying structural determinants associated with GH13 family reaction specificity is key to modifying and designing enzymes with increased specificity towards individual reactions for further applications in industrial, chemical, or biomedical fields. This work proposes a computational approach for decoding the determinant structural composition defining the reaction specificity. This method is based on the conservation of coevolving residues in spatial contacts associated with reaction specificity. To evaluate the algorithm, mutants of α-amylase (TmAmyA) and glucanotransferase (TmGTase) from Thermotoga maritima were constructed to modify the reaction specificity. The K98P/D99A/H222Q variant from TmAmyA doubled the transglycosydation/hydrolysis (T/H) ratio while the M279N variant from TmGTase increased the hydrolysis/transglycosidation ratio five-fold. Molecular dynamic simulations of the variants indicated changes in flexibility that can account for the modified T/H ratio. An essential contribution of the presented computational approach is its capacity to identify residues outside of the active center that affect the reaction specificity.
Identification of Nutritional Ingredients and Medicinal Components of Pueraria lobata and Its Varieties Using UPLC-MS/MS-Based Metabolomics
Authors: Shang Xiaohong , Huang Ding , Wang Ying , Xiao Liang , Ming Ruhong , Zeng Wendan , Cao Sheng , Lu Liuying , Wu Zhengdan , Yan Huabing
Published: November 2021

Pueraria lobata and its variety P. lobata var. thomsonii are both traditional Chinese medicines that have high nutritional and medical value; whereas another variety, P. lobata var. montana has low nutritional and medicinal value and can cause ecological disasters. The material basis of different nutritional and medicinal values, which are caused by metabolite differences among these varieties, remains to be further clarified. Here, we performed ultra performance liquid chromatography-tandem mass spectrometry based widely targeted metabolome analysis on Pueraria lobata, P. lobata var. thomsonii, and P. lobata var. montana. Among them, a total of 614 metabolites were identified, and distinguished from each other using orthogonal partial least squares discriminant analysis. Our results suggest that the nutritional differences between P. lobata and its varieties can be explained by variations in the abundance of amino acids, nucleotides, saccharides, and lipids; differences in flavonoids, isoflavones, phenolic acids, organic acids, and coumarins contents caused the differences in the medicinal quality of P. lobata and its varieties. Additionally, the key metabolites responsible for the classification of the three Pueraria varieties were identified. This study provides new insights into the underlying metabolic causes of nutritional and medicinal variation in P. lobata and its varieties.
Luteapyrone, a Novel ƴ-Pyrone Isolated from the Filamentous Fungus Metapochonia lutea
Authors: Labuda Roman , Bacher Markus , Gratzl Hannes , Doppler Maria , Parich Alexandra , Aufy Mohammed , Lemmens-Gruber Rosa , Schuhmacher Rainer , Rychli Kathrin , Wagner Martin , Rosenau Thomas , Strauss Joseph , Schüller Christoph
Published: November 2021

In the process of screening for new bioactive microbial metabolites we found a novel ƴ-pyrone derivative for which we propose the trivial name luteapyrone, in a recently described microscopic filamentous fungus, Metapochonia lutea BiMM-F96/DF4. The compound was isolated from the culture extract of the fungus grown on modified yeast extract sucrose medium by means of flash chromatography followed by preparative HPLC. The chemical structure was elucidated by NMR and LC-MS. The new compound was found to be non-cytotoxic against three mammalian cell lines (HEK 263, KB-3.1 and Caco-2). Similarly, no antimicrobial activity was observed in tested microorganisms (gram positive and negative bacteria, yeast and fungi).
Thermomechanical Buckling Analysis of the E&P-FGM Beams Integrated by Nanocomposite Supports Immersed in a Hygrothermal Environment
Authors: Khorasani Mohammad , Lampani Luca , Dimitri Rossana , Tornabene Francesco
Published: November 2021

Due to the widespread use of sandwich structures in many industries and the importance of understanding their mechanical behavior, this paper studies the thermomechanical buckling behavior of sandwich beams with a functionally graded material (FGM) middle layer and two composite external layers. Both composite skins are made of Poly(methyl methacrylate) (PMMA) reinforced by carbon-nano-tubes (CNTs). The properties of the FGM core are predicted through an exponential-law and power-law theory (E&P), whereas an Eshelby–Mori–Tanaka (EMT) formulation is applied to capture the mechanical properties of the external layers. Moreover, different high-order displacement fields are combined with a virtual displacement approach to derive the governing equations of the problem, here solved analytically based on a Navier-type approximation. A parametric study is performed to check for the impact of different core materials and CNT concentrations inside the PMMA on the overall response of beams resting on a Pasternak substrate and subjected to a hygrothermal loading. This means that the sensitivity analysis accounts for different displacement fields, hygrothermal environments, and FGM theories, as a novel aspect of the present work. Our results could be replicated in a computational sense, and could be useful for design purposes in aerospace industries to increase the tolerance of target productions, such as aircraft bodies.
Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region
Authors: Wickhorst Peter Jonas , Ihmels Heiko , Paululat Thomas
Published: November 2021

Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biological activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence a2 with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium (1), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of a2 with four stacked guanine quartets. Furthermore, ligand 1 has high affinity toward a2 and binds by terminal π stacking to the G1–G11–G15–G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of a2.
Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles
Authors: Afonso Urich Jesús Alberto , Marko Viktoria , Boehm Katharina , Lara García Raymar Andreína , Jeremic Dalibor , Paudel Amrit
Published: November 2021

A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC®) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50–6.50 µg/mL (R2 = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.
Shear-Induced Crystallization of Star and Linear Poly(L-lactide)s
Authors: Bojda Joanna , Piorkowska Ewa , Lapienis Grzegorz , Michalski Adam
Published: November 2021

The influence of macromolecular architecture on shear-induced crystallization of poly(L-lactide) (PLLA) was studied. To this aim, three star PLLAs, 6-arm with Mw of 120 and 245 kg/mol, 4-arm with Mw of 123 kg/mol, and three linear PLLAs with Mw of 121, 240 and 339 kg/mol, were synthesized and examined. The PLLAs were sheared at 170 and 150 °C, at 5/s, 10/s and 20/s for 20 s, 10 s and 5 s, respectively, and then cooled at 10 or 30 °C/min. Shear-induced crystallization during cooling was followed by a light depolarization method, whereas the crystallized specimens were examined by DSC, 2D-WAXS, 2D-SAXS and SEM. The effect of shear depended on the shearing conditions, cooling rate and polymer molar mass but it was also affected by the macromolecular architecture. The shear-induced crystallization of linear PLLA with Mw of 240 kg/mol was more intense than that of the 6-arm polymer with similar Mw, most possibly due to its higher Mz. However, the influence of shear on the crystallization of the star polymers with Mw close to 120 kg/mol was stronger than on that of their linear analog. This was reflected in higher crystallization temperature, as well as crystallinity achieved during cooling.
Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats
Authors: Baeeri Maryam , Didari Tina , Khalid Madiha , Mohammadi-Nejad Solmaz , Daghighi Seyed Mojtaba , Farhadi Ramtin , Rahimifard Mahban , Bayrami Zahra , Haghi-Aminjan Hamed , Foroumadi Roham , Gholami Mahdi , Abdollahi Mohammad
Published: November 2021

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.
Zinc as a Drug for Wilson’s Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury
Authors: Coni Pierpaolo , Pichiri Giuseppina , Lachowicz Joanna Izabela , Ravarino Alberto , Ledda Francesca , Fanni Daniela , Gerosa Clara , Piras Monica , Coghe Ferdinando , Gibo Yukio , Cau Flaviana , Castagnola Massimo , Van Eyken Peter , Saba Luca , Piludu Marco , Faa Gavino
Published: November 2021

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson’s disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson’s disease. On the basis of the similarities, at histological level, between Wilson’s disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.
Robust Saliva-Based RNA Extraction-Free One-Step Nucleic Acid Amplification Test for Mass SARS-CoV-2 Monitoring
Authors: Rajh Eva , Šket Tina , Praznik Arne , Sušjan Petra , Šmid Alenka , Urbančič Dunja , Mlinarič-Raščan Irena , Kogovšek Polona , Demšar Tina , Milavec Mojca , Prosenc Trilar Katarina , Jensterle Žiga , Zidarn Mihaela , Tomič Viktorija , Turel Gabriele , Lejko-Zupanc Tatjana , Jerala Roman , Benčina Mojca
Published: November 2021

Early diagnosis with rapid detection of the virus plays a key role in preventing the spread of infection and in treating patients effectively. In order to address the need for a straightforward detection of SARS-CoV-2 infection and assessment of viral spread, we developed rapid, sensitive, extraction-free one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP) tests for detecting SARS-CoV-2 in saliva. We analyzed over 700 matched pairs of saliva and nasopharyngeal swab (NSB) specimens from asymptomatic and symptomatic individuals. Saliva, as either an oral cavity swab or passive drool, was collected in an RNA stabilization buffer. The stabilized saliva specimens were heat-treated and directly analyzed without RNA extraction. The diagnostic sensitivity of saliva-based RT-qPCR was at least 95% in individuals with subclinical infection and outperformed RT-LAMP, which had at least 70% sensitivity when compared to NSBs analyzed with a clinical RT-qPCR test. The diagnostic sensitivity for passive drool saliva was higher than that of oral cavity swab specimens (95% and 87%, respectively). A rapid, sensitive one-step extraction-free RT-qPCR test for detecting SARS-CoV-2 in passive drool saliva is operationally simple and can be easily implemented using existing testing sites, thus allowing high-throughput, rapid, and repeated testing of large populations. Furthermore, saliva testing is adequate to detect individuals in an asymptomatic screening program and can help improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2
Authors: Qiao Yanan , Qin Yuxi , Liu Lihua , Chen Xi , Li Yunlan , Li Qingshan
Published: November 2021

Cyclooxygenases 2 (COX2) is a therapeutic target for many inflammation and oxidative stress associated diseases. A high-throughput technique, biolayer interferometry, was performed to primarily screen the potential COX2 binding activities of twelve newly synthesized double hydroxide-based benzophenone derivatives. Binding confirmation was achieved by molecular docking and multi-spectroscopy studies. Such a combined method provided a comprehensive understanding of binding mechanism and conformational changes. Compounds DB2, SC2 and YB2 showed effective COX2 binding activity and underlined the benefits of three phenolic hydroxyl groups adjacent to each other on the B ring. The twelve tested derivatives were further evaluated for antioxidant activity, wherein compound SC2 showed the highest activity. Its concentration for the 50% of maximal effect (EC50) value was approximately 1000 times greater than that of the positive controls. SC2 treatment effectively improved biochemical indicators caused by oxidative stress. Overall, compound SC2 could serve as a promising candidate for further development of a new potent COX2 inhibitor.
In Honor of John Bannister Goodenough, an Outstanding Visionary
Authors: Etourneau Jean , Delmas Claude , Jobic Stéphane , Whangbo Myung-Hwan
Published: November 2021

John B [...]
Optimization of a Multiresidue Analysis of 65 Pesticides in Surface Water Using Solid-Phase Extraction by LC-MS/MS
Authors: Nakhjavan Bahar , Bland Jason , Khosravifard Maryam
Published: November 2021

An analytical method was developed and validated for simultaneous quantitation of 65 pesticides, including one single solid-phase extraction (SPE) procedure in surface water by liquid chromatography coupled to tandem mass spectroscopy. Different parameters that have an influence on extraction efficiency were evaluated in this research. Different types of cartridges, elution solvents, and sorbent drying time were investigated, and the most appropriate one was selected. Moreover, various pretreatment techniques were applied to remove sediments from water without the loss of pesticides. Centrifugation was introduced as the best option at the beginning of sample preparation to resolve the clogging of the sorbent cartridges. The recoveries of all pesticides ranged from 70% to 120%, with a relative standard deviation of less than 13.7%. The feasibility of the method was evaluated on 10 surface water samples with different concentrations of sand, sediment, and particles.
Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core
Authors: Mamat Constantin , Jentschel Christian , Köckerling Martin , Steinbach Jörg
Published: November 2021

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.
Warfarin Sodium Stability in Oral Formulations
Authors: Dimitrokalli Evangelia , Fertaki Stefani , Lykouras Michail , Kokkinos Petros , Orkoula Malvina , Kontoyannis Christos
Published: November 2021

Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent instability of the commercially available warfarin liquid oral formulation using Raman and IR spectroscopy, X-ray diffraction, differential scanning calorimetry, UV spectroscopy, and optical microscopy. Warfarin, not its sodium salt, was identified as the undissolved solid existing in the suspension. This was found to be due to the dissociation of sodium salt and the protonation of the warfarin ion in the liquid phase, which triggered the crystallization of the sparingly soluble unsalted form. The coexistence of protonated and unprotonated warfarin ions in the supernatant, as detected by Raman and UV spectroscopy, confirmed this assumption. Study of the dissolution of warfarin sodium amorphous salt and crystalline sodium clathrate in the placebo and pure water verified the results. The effect of pH and temperature on warfarin precipitation was also explored.
Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies
Authors: Usman Faisal , Shah Hamid Saeed , Zaib Sumera , Manee Sirikhwan , Mudassir Jahanzeb , Khan Ajmal , Batiha Gaber El-Saber , Abualnaja Khamael M. , Alhashmialameer Dalal , Khan Imtiaz
Published: November 2021

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.
Music and Time Perception in Audiovisuals: Arousing Soundtracks Lead to Time Overestimation No Matter Their Emotional Valence
Authors: Ansani Alessandro , Marini Marco , Mallia Luca , Poggi Isabella
Published: November 2021

One of the most tangible effects of music is its ability to alter our perception of time. Research on waiting times and time estimation of musical excerpts has attested its veritable effects. Nevertheless, there exist contrasting results regarding several musical features’ influence on time perception. When considering emotional valence and arousal, there is some evidence that positive affect music fosters time underestimation, whereas negative affect music leads to overestimation. Instead, contrasting results exist with regard to arousal. Furthermore, to the best of our knowledge, a systematic investigation has not yet been conducted within the audiovisual domain, wherein music might improve the interaction between the user and the audiovisual media by shaping the recipients’ time perception. Through the current between-subjects online experiment (n = 565), we sought to analyze the influence that four soundtracks (happy, relaxing, sad, scary), differing in valence and arousal, exerted on the time estimation of a short movie, as compared to a no-music condition. The results reveal that (1) the mere presence of music led to time overestimation as opposed to the absence of music, (2) the soundtracks that were perceived as more arousing (i.e., happy and scary) led to time overestimation. The findings are discussed in terms of psychological and phenomenological models of time perception.
APTES-Based Silica Nanoparticles as a Potential Modifier for the Selective Sequestration of CO2 Gas Molecules
Authors: Cueto-Díaz Eduardo J. , Castro-Muñiz Alberto , Suárez-García Fabián , Gálvez-Martínez Santos , Torquemada-Vico Mª Carmen , Valles-González Mª Pilar , Mateo-Martí Eva
Published: November 2021

In this work, we have described the characterization of hybrid silica nanoparticles of 50 nm size, showing outstanding size homogeneity, a large surface area, and remarkable CO2 sorption/desorption capabilities. A wide battery of techniques was conducted ranging from spectroscopies such as: UV-Vis and IR, to microscopies (SEM, AFM) and CO2 sorption/desorption isotherms, thus with the purpose of the full characterization of the material. The bare SiO2 (50 nm) nanoparticles modified with 3-aminopropyl (triethoxysilane), APTES@SiO2 (50 nm), show a remarkable CO2 sequestration enhancement compared to the pristine material (0.57 vs. 0.80 mmol/g respectively at 50 °C). Furthermore, when comparing them to their 200 nm size counterparts (SiO2 (200 nm) and APTES@SiO2 (200 nm)), there is a marked CO2 capture increment as a consequence of their significantly larger micropore volume (0.25 cm3/g). Additionally, ideal absorbed solution theory (IAST) was conducted to determine the CO2/N2 selectivity at 25 and 50 °C of the four materials of study, which turned out to be >70, being in the range of performance of the most efficient microporous materials reported to date, even surpassing those based on silica.
Exploiting the Potential of Supported Magnetic Nanomaterials as Fenton-Like Catalysts for Environmental Applications
Authors: González-Rodríguez Jorge , Gamallo María , Conde Julio J. , Vargas-Osorio Zulema , Vázquez-Vázquez Carlos , Piñeiro Yolanda , Rivas José , Feijoo Gumersindo , Moreira Maria Teresa
Published: November 2021

In recent years, the application of magnetic nanoparticles as alternative catalysts to conventional Fenton processes has been investigated for the removal of emerging pollutants in wastewater. While this type of catalyst reduces the release of iron hydroxides with the treated effluent, it also presents certain disadvantages, such as slower reaction kinetics associated with the availability of iron and mass transfer limitations. To overcome these drawbacks, the functionalization of the nanocatalyst surface through the addition of coatings such as polyacrylic acid (PAA) and their immobilization on a mesoporous silica matrix (SBA15) can be factors that improve the dispersion and stability of the nanoparticles. Under these premises, the performance of the nanoparticle coating and nanoparticle-mesoporous matrix binomials in the degradation of dyes as examples of recalcitrant compounds were evaluated. Based on the outcomes of dye degradation by the different functionalized nanocatalysts and nanocomposites, the nanoparticles embedded in a mesoporous matrix were applied for the removal of estrogens (E1, E2, EE2), accomplishing high removal percentages (above 90%) after the optimization of the operational variables. With the feasibility of their recovery in mind, the nanostructured materials represented a significant advantage as their magnetic character allows their separation for reuse in different successive sequential batch cycles.
Genetic Algorithm-Driven Surface-Enhanced Raman Spectroscopy Substrate Optimization
Authors: Bilgin Buse , Yanik Cenk , Torun Hulya , Onbasli Mehmet Cengiz
Published: November 2021

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive and molecule-specific detection technique that uses surface plasmon resonances to enhance Raman scattering from analytes. In SERS system design, the substrates must have minimal or no background at the incident laser wavelength and large Raman signal enhancement via plasmonic confinement and grating modes over large areas (i.e., squared millimeters). These requirements impose many competing design constraints that make exhaustive parametric computational optimization of SERS substrates prohibitively time consuming. Here, we demonstrate a genetic-algorithm (GA)-based optimization method for SERS substrates to achieve strong electric field localization over wide areas for reconfigurable and programmable photonic SERS sensors. We analyzed the GA parameters and tuned them for SERS substrate optimization in detail. We experimentally validated the model results by fabricating the predicted nanostructures using electron beam lithography. The experimental Raman spectrum signal enhancements of the optimized SERS substrates validated the model predictions and enabled the generation of a detailed Raman profile of methylene blue fluorescence dye. The GA and its optimization shown here could pave the way for photonic chips and components with arbitrary design constraints, wavelength bands, and performance targets.
Systematic Assessment of Visible-Light-Driven Microspherical V2O5 Photocatalyst for the Removal of Hazardous Organosulfur Compounds from Diesel
Authors: Shafiq Iqrash , Hussain Murid , Shafique Sumeer , Akhter Parveen , Ahmed Ashfaq , Ashraf Raja Shahid , Ali Khan Moonis , Jeon Byong-Hun , Park Young-Kwon
Published: November 2021

The organosulfur compounds present in liquid fuels are hazardous for health, asset, and the environment. The photocatalytic desulfurization technique works at ordinary conditions and removes the requirement of hydrogen, as it is an expensive gas, highly explosive, with a broader flammability range and is declared the most hazardous gas within a petroleum refinery, with respect to flammability. The projected work is based on the synthesis of V2O5 microspheres for photocatalytic oxidation for the straight-run diesel (SRD) and diesel oil blend (DOB). The physicochemical properties of V2O5 microspheres were examined by FT-IR, Raman, UV-vis DRS, SEM, and Photoluminescence evaluations. The as-synthesized photocatalyst presented a trivial unit size, a narrow bandgap, appropriate light-capturing capability, and sufficient active sites. The desulfurization study discovered that the anticipated technique is substantial in desulfurizing DOB up to 37% in 180 min using methanol as an interfacing agent. Furthermore, the outcome of employing a range of polar interfacing solvents was examined, and the 2-ethoxyethanol elevated the desulfurization degree up to 51.3%. However, the anticipated technology is constrained for its application in sulfur removal from SRD. Additionally, the mechanism for a photocatalytic reaction was seen in strong agreement with pseudo-first-order kinetics. The investigated photocatalyst exhibited a compromised recyclability and regeneration tendency.
Vertically Aligned Binder-Free TiO2 Nanotube Arrays Doped with Fe, S and Fe-S for Li-ion Batteries
Authors: Dasarathan Suriyakumar , Ali Mukarram , Jung Tai-Jong , Sung Junghwan , Ha Yoon-Cheol , Park Jun-Woo , Kim Doohun
Published: November 2021

Vertically aligned Fe, S, and Fe-S doped anatase TiO2 nanotube arrays are prepared by an electrochemical anodization process using an organic electrolyte in which lactic acid is added as an additive. In the electrolyte, highly ordered TiO2 nanotube layers with greater thickness of 12 μm, inner diameter of approx. 90 nm and outer diameter of approx. 170 nm are successfully obtained. Doping of Fe, S, and Fe-S via simple wet impregnation method substituted Ti and O sites with Fe and S, which leads to enhance the rate performance at high discharge C-rates. Discharge capacities of TiO2 tubes increased from 0.13 mAh cm−2(bare) to 0.28 mAh cm−2 for Fe-S doped TiO2 at 0.5 C after 100 cycles with exceptional capacity retention of 85 % after 100 cycles. Owing to the enhancement of thermodynamic and kinetic properties by doping of Fe-S, Li-diffusion increased resulting in remarkable discharge capacities of 0.27 mAh cm−2 and 0.16 mAh cm−2 at 10 C, and 30 C, respectively.
Deficiency in the Essential Amino Acids l-Isoleucine, l-Leucine and l-Histidine and Clinical Measures as Predictors of Moderate Depression in Elderly Women: A Discriminant Analysis Study
Authors: Solís-Ortiz Silvia , Arriaga-Avila Virginia , Trejo-Bahena Aurora , Guevara-Guzmán Rosalinda
Published: November 2021

Increases in depression are common in some elderly women. Elderly women often show moderate depressive symptoms, while others display minimal depressive symptoms. These discrepancies have produced contradictory and inconclusive outcomes, which have not been explained entirely by deficits in neurotransmitter precursors. Deficiency in some amino acids have been implicated in major depression, but its role in non-clinical elderly women is not well known. An analysis of essential amino acids, depression and the use of discriminant analysis can help to clarify the variation in depressive symptoms exhibited by some elderly women. The aim was to investigate the relationship of essential amino acids with affective, cognitive and comorbidity measures in elderly women without major depression nor severe mood disorders or psychosis, specifically thirty-six with moderate depressive symptoms and seventy-one with minimal depressive symptoms. The plasma concentrations of nineteen amino acids, Beck Depression Inventory (BDI) scores, Geriatric Depression Scale (GDS) scores, global cognitive scores and comorbidities were submitted to stepwise discriminant analysis to identify predictor variables. Seven predictors arose as important for belong to the group based on amino acid concentrations, with the moderate depressive symptoms group characterized by higher BDI, GDS and cognitive scores; fewer comorbidities; and lower levels of l-histidine, l-isoleucine and l-leucine. These findings suggest that elderly women classified as having moderate depressive symptoms displayed a deficiency in essential amino acids involved in metabolism, protein synthesis, inflammation and neurotransmission.