bluuebunny/crossref_metadata_2025 huggingface dataset:
The Second Life of Citrus Fruit Waste: A Valuable Source of Bioactive Compounds
Authors: Russo Caterina , Maugeri Alessandro , Lombardo Giovanni Enrico , Musumeci Laura , Barreca Davide , Rapisarda Antonio , Cirmi Santa , Navarra Michele
Published: October 2021

Citrus fruits (CF) are among the most widely cultivated fruit crops throughout the world and their production is constantly increasing along with consumers’ demand. Therefore, huge amounts of waste are annually generated through CF processing, causing high costs for their disposal, as well as environmental and human health damage, if inappropriately performed. According to the most recent indications of an economic, environmental and pharmaceutical nature, CF processing residues must be transformed from a waste to be disposed to a valuable resource to be reused. Based on a circular economy model, CF residues (i.e., seeds, exhausted peel, pressed pulp, secondary juice and leaves) have increasingly been re-evaluated to also obtain, but not limited to, valuable compounds to be employed in the food, packaging, cosmetic and pharmaceutical industries. However, the use of CF by-products is still limited because of their underestimated nutritional and economic value, hence more awareness and knowledge are needed to overcome traditional approaches for their disposal. This review summarizes recent evidence on the pharmacological potential of CF waste to support the switch towards a more environmentally sustainable society.
Semi-Rigid (Aminomethyl) Piperidine-Based Pentadentate Ligands for Mn(II) Complexation
Authors: Martinelli Jonathan , Callegari Edoardo , Baranyai Zsolt , Fraccarollo Alberto , Cossi Maurizio , Tei Lorenzo
Published: October 2021

Two pentadentate ligands built on the 2-aminomethylpiperidine structure and bearing two tertiary amino and three oxygen donors (three carboxylates in the case of AMPTA and two carboxylates and one phenolate for AMPDA-HB) were developed for Mn(II) complexation. Equilibrium studies on the ligands and the Mn(II) complexes were carried out using pH potentiometry, 1H-NMR spectroscopy and UV-vis spectrophotometry. The Mn complexes that were formed by the two ligands were more stable than the Mn complexes of other pentadentate ligands but with a lower pMn than Mn(EDTA) and Mn(CDTA) (pMn for Mn(AMPTA) = 7.89 and for Mn(AMPDA-HB) = 7.07). 1H and 17O-NMR relaxometric studies showed that the two Mn-complexes were q = 1 with a relaxivity value of 3.3 mM−1 s−1 for Mn(AMPTA) and 3.4 mM−1 s−1 for Mn(AMPDA-HB) at 20 MHz and 298 K. Finally, the geometries of the two complexes were optimized at the DFT level, finding an octahedral coordination environment around the Mn2+ ion, and MD simulations were performed to monitor the distance between the Mn2+ ion and the oxygen of the coordinated water molecule to estimate its residence time, which was in good agreement with that determined using the 17O NMR data.
The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons
Authors: Araújo Hallysson Douglas Andrade de , Silva Hianna Arely Milca Fagundes , Silva Júnior José Guedes da , Albuquerque Mônica Camelo Pessoa de Azevedo , Coelho Luana Cassandra Breitenbach Barroso , Aires André de Lima
Published: October 2021

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.
Bioactive Compounds from Ephedra fragilis: Extraction Optimization, Chemical Characterization, Antioxidant and AntiGlycation Activities
Authors: Guenaou Ismail , Nait Irahal Imane , Errami Ahmed , Lahlou Fatima Azzahra , Hmimid Fouzia , Bourhim Noureddine
Published: October 2021

Response surface methodology (RSM) with a Box–Behnken design (BBD) was used to optimize the extraction of bioactive compounds from Ephedra fragilis. The results suggested that extraction with 61.93% ethanol at 44.43 °C for 15.84 h was the best solution for this combination of variables. The crude ethanol extract (CEE) obtained under optimum extraction conditions was sequentially fractionated with solvents of increasing polarity. The content of total phenolic (TP) and total flavonoid (TF) as well as the antioxidant and antiglycation activities were measured. The phytochemical fingerprint profile of the fraction with the highest activity was characterized by using RP-HPLC. The ethyl acetate fraction (EAF) had the highest TP and TF contents and exhibited the most potent antioxidant and antiglycation activities. The Pearson correlation analysis results showed that TP and TF contents were highly significantly correlated with the antioxidant and antiglycation activities. Totally, six compounds were identified in the EAF of E. fragilis, including four phenolic acids and two flavonoids. Additionally, molecular docking analysis also showed the possible connection between identified bioactive compounds and their mechanisms of action. Our results suggest new evidence on the antioxidant and antiglycation activities of E. fragilis bioactive compounds that may be applied in the treatment and prevention of aging and glycation-associated complications.
Synthesis, Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives
Authors: Katopodi Annita , Tsotsou Evangelia , Iliou Triantafylia , Deligiannidou Georgia-Eirini , Pontiki Eleni , Kontogiorgis Christos , Tsopelas Fotios , Detsi Anastasia
Published: October 2021

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.
The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation
Authors: Ruzgys Paulius , Barauskaitė Neringa , Novickij Vitalij , Novickij Jurij , Šatkauskas Saulius
Published: October 2021

One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of the bystander effect following these electroporation-based treatments. During direct CHO-K1 cell treatment, cells were electroporated using one 100 µs duration square wave electric pulse at 1400 V/cm (for bleomycin electrotransfer) or 2800 V/cm (for irreversible electroporation). To evaluate the bystander effect, the medium was taken from directly treated cells after 24 h incubation and applied on unaffected cells. Six days after the treatment, cell viability and colony sizes were evaluated using the cell colony formation assay. The results showed that the bystander effect after bleomycin electrotransfer had a strong negative impact on cell viability and cell colony size, which decreased to 2.8% and 23.1%, respectively. On the contrary, irreversible electroporation induced a strong positive bystander effect on cell viability, which increased to 149.3%. In conclusion, the results presented may serve as a platform for further analysis of the bystander effect after electroporation-based therapies and may ultimately lead to refined application of these therapies in clinics.
Overexpression of the Gene Encoding Neurosecretory Protein GL Precursor Prevents Excessive Fat Accumulation in the Adipose Tissue of Mice Fed a Long-Term High-Fat Diet
Authors: Fukumura Keisuke , Narimatsu Yuki , Moriwaki Shogo , Iwakoshi-Ukena Eiko , Furumitsu Megumi , Ukena Kazuyoshi
Published: October 2021

We previously identified a novel small hypothalamic protein, neurosecretory protein GL (NPGL), which induces feeding behavior and fat accumulation in rodents depending on their diet. In the present study, we explored the effects of NPGL on feeding behavior and energy metabolism in mice placed on a long-term high-fat diet with 60% calories from fat (HFD 60). Overexpression of the NPGL precursor gene (Npgl) over 18 weeks increased food intake and weight. The weekly weight gain of Npgl-overexpressing mice was higher than that of controls until 7 weeks from induction of overexpression, after which it ceased to be so. Oral glucose tolerance tests showed that Npgl overexpression maintained glucose tolerance and increased blood insulin levels, and intraperitoneal insulin tolerance tests showed that it maintained insulin sensitivity. At the experimental endpoint, Npgl overexpression was associated with increased mass of the perirenal white adipose tissue (WAT) and decreased mass of the epididymal WAT (eWAT), resulting in little effect on the total WAT mass. These results suggest that under long-term HFD 60 feeding, Npgl overexpression may play a role in avoiding metabolic disturbance both by accelerating energy storage and by suppressing excess fat accumulation in certain tissues, such as the eWAT.
On the Squalene Content of CV Chondrolia Chalkidikis and Chalkidiki (Greece) Virgin Olive Oil
Authors: Mastralexi Aspasia , Tsimidou Maria Z.
Published: October 2021

This work is a continuation of efforts to establish the nutritional profile of virgin olive oil (VOO) from cv. Chondrolia Chalkidikis and Chalkidiki and to strengthen its positioning in the global VOO landscape. VOOs produced at an industrial scale in different olive mills of the Chalkidiki (Greece) regional unit as well as VOOs obtained at the laboratory scale from drupes of different maturity stages for four consecutive harvesting years were examined for their squalene (SQ) content using both HPLC and GC procedures. The mean values of SQ were found to be 4228 (HPLC) and 4865 (GC) mg/kg oil (n = 15) and were of the same magnitude as that in VOOs from cv Koroneiki (4134 mg/kg, n = 23). Storage of VOOs in the dark at room temperature for 18 months indicated an insignificant mean SQ content loss (~2%) in comparison to a mean loss of 26% for alpha-tocopherol content. This finding strengthens our view that SQ does not act as a radical scavenger that donates hydrogen atoms to the latter. The four consecutive harvest years studied indicated a clear declining trend in VOO SQ concentration upon olive ripening. To our knowledge, this is the first systematic work concerning the SQ content of Chondrolia Chalkidikis and Chalkidiki VOOs.
Improved Stability of a Stable Crystal Form C of 6S-5-Methyltetrahydrofolate Calcium Salt, Method Development and Validation of an LC–MS/MS Method for Rat Pharmacokinetic Comparison
Authors: Lian Zenglin , Chen Hong , Liu Kang , Jia Qianghua , Qiu Feng , Cheng Yongzhi
Published: October 2021

Folate is a vitamin beneficial for humans that plays an important role in metabolism, but it cannot be well supplemented by food; it is necessary to supplement it in other ways. Based on this consideration, a novel crystal form C of 6S-5-methyltetrahydrofolate calcium salt (MTHF CAC) was obtained. To explore the difference between MTHF CAC and the crystal form Ⅰ of 6S-5-methyltetrahydrofolate calcium salt (MTHF CA) as well as an amorphous product of 6S-5-methyltetrahydrofolate glucosamine salt (MTHF GA), their stability and pharmacokinetic behaviours were compared. The results of high-performance liquid chromatography coupled with ultraviolet detection analysis indicated that MTHF CAC showed a better stability than MTHF CA and MTHF GA. After oral administration of MTHF CAC, MTHF CA, and MTHF GA to male rats, the MTHF concentrations were analysed using a validated liquid chromatography–tandem mass spectrometry, and the pharmacokinetic parameters were compared. The mean residence times (0–t) of MTHF CAC, MTHF CA, and MTHF GA were 3.7 ± 1.9 h, 1.0 ± 0.2 h (p < 0.01), and 1.5 ± 0.3 h (p < 0.05), respectively. The relative bioavailability of MTHF CAC was calculated to be 351% and 218% compared with MTHF CA and MTHF GA, respectively, which suggests that MTHF CAC can be better absorbed and utilized for a longer period of time.
Structural Basis for PPARs Activation by The Dual PPARα/γ Agonist Sanguinarine: A Unique Mode of Ligand Recognition
Authors: Tian Siyu , Wang Rui , Chen Shuming , He Jialing , Zheng Weili , Li Yong
Published: October 2021

Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARα and PPARγ, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARα/γ. Similar to fenofibrate, sanguinarine upregulates the expression of PPARα-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARγ-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARα, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARα. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARα/γ among all three PPARs. In summary, our study identifies a PPARα/γ dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands.
Analytical Assessment of Bioelements in Various Types of Black Teas from Different Geographical Origins in View of Chemometric Approach
Authors: Koch Wojciech , Kukula-Koch Wirginia , Czop Marcin , Baj Tomasz , Kocki Janusz , Bawiec Piotr , Casasnovas Roser Olives , Głowniak-Lipa Anna , Głowniak Kazimierz
Published: October 2021

A comprehensive approach to the mineral composition of black teas of different origins was studied using the Flame Atomic Absorption Spectrometry (FAAS) method, supported by chemometric tools including Principal Component Analysis PCA) and Classification and Regression Trees (CART). Significant differences between the teas from seven countries (Japan, Nepal, Kenya, Iran, Sri Lanka, India, and China) were shown. K was the main element determined in all teas, with an average concentration of 11,649 mg/kg, followed by Ca, Mg and Mn. In general, regarding all investigated black teas, the element content was ranked in the following order: K > Ca > Mg > Mn > Fe > Na > Zn > Cu. The applied chemometric methods allowed us to recognize black tea clusters based on their mineral composition and place of cultivation, and allowed us to find correlations between particular elements in black teas. The performed analyses revealed interesting correlations between the concentration of various elements in black teas: K was negatively correlated with Na, Fe, Mn and Cu; K was positively correlated with the content of Ca and Mg. Significant positive correlations between Mn and Fe and Mn and Zn in the studied black tea samples were also revealed. It was shown that mineral composition may be a significant factor regarding the origin of the black tea, not only considering the country, but also the region or province.
Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development
Authors: Aljanabi Reem , Alsous Lina , Sabbah Dima A. , Gul Halise Inci , Gul Mustafa , Bardaweel Sanaa K.
Published: October 2021

Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.
Crystal Structure and Magnetic Properties of Trinuclear Transition Metal Complexes (MnII, CoII, NiII and CuII) with Bridging Sulfonate-Functionalized 1,2,4-Triazole Derivatives
Authors: Moneo-Corcuera Andrea , Pato-Doldan Breogán , Sánchez-Molina Irene , Nieto-Castro David , Galán-Mascarós José Ramón
Published: October 2021

Here we present the synthesis, structure and magnetic properties of complexes of general formula (Mn)(Me2NH2)4][Mn3(μ-L)6(H2O)6] and (Me2NH2)6[M3(μ-L)6(H2O)6] (M = CoII, NiII and CuII); L−2 = 4-(1,2,4-triazol-4-yl) ethanedisulfonate). The trinuclear polyanions were isolated as dimethylammonium salts, and their crystal structures determined by single crystal and powder X-ray diffraction data. The polyanionic part of these salts have the same molecular structure, which consists of a linear array of metal(II) ions linked by triple N1-N2-triazole bridges. In turn, the composition and crystal packing of the MnII salt differs from the rest of the complexes (with six dimethyl ammonia as countercations) in containing one Mn+2 and four dimethyl ammonia as countercations. Magnetic data indicate dominant intramolecular antiferromagnetic interactions stabilizing a paramagnetic ground state. Susceptibility data have been successfully modeled with a simple isotropic Hamiltonian for a centrosymmetric linear trimer, H = −2J (S1S2 + S2S3) with super-exchange parameters J = −0.4 K for MnII, −7.5 K for NiII and −45 K for CuII complex. The magnetic properties of these complexes and their easy processing opens unique possibilities for their incorporation as magnetic molecular probes into such hybrid materials as magnetic/conducting multifunctional materials or as dopant for organic conducting polymers.
Peptaibol-Containing Extracts of Trichoderma atroviride and the Fight against Resistant Microorganisms and Cancer Cells
Authors: Víglaš Ján , Dobiasová Simona , Viktorová Jitka , Ruml Tomáš , Repiská Vanda , Olejníková Petra , Gbelcová Helena
Published: October 2021

Fighting resistance to antibiotics and chemotherapeutics has brought bioactive peptides to the fore. Peptaibols are short α-aminoisobutyric acid-containing peptides produced by Trichoderma species. Here, we studied the production of peptaibols by Trichoderma atroviride O1 and evaluated their antibacterial and anticancer activity against drug-sensitive and multidrug-resistant bacterium and cancer cell lines. This was substantiated by an analysis of the activity of the peptaibol synthetase-encoding gene. Atroviridins, 20-residue peptaibols were detected using MALDI-TOF mass spectrometry. Gram-positive bacteria were susceptible to peptaibol-containing extracts of T. atroviride O1. A synergic effect of extract constituents was possible, and the biolo-gical activity of extracts was pronounced in/after the peak of peptaibol synthetase activity. The growth of methicillin-resistant Staphylococcus aureus was reduced to just under 10% compared to the control. The effect of peptaibol-containing extracts was strongly modulated by the lipoteichoic acid and only slightly by the horse blood serum present in the cultivation medium. Peptaibol-containing extracts affected the proliferation of human breast cancer and human ovarian cancer cell lines in a 2D model, including the multidrug-resistant sublines. The peptaibols influenced the size and compactness of the cell lines in a 3D model. Our findings indicate the molecular basis of peptaibol production in T. atroviride O1 and the potential of its peptaibol-containing extracts as antimicrobial/anticancer agents.
Solvent Mixture Optimization in the Extraction of Bioactive Compounds and Antioxidant Activities from Garlic (Allium sativum L.)
Authors: Cavalcanti Vytória Piscitelli , Aazza Smail , Bertolucci Suzan Kelly Vilela , Rocha João Pedro Miranda , Coelho Adriane Duarte , Oliveira Altino Júnior Mendes , Mendes Laís Campelo , Pereira Maysa Mathias Alves , Morais Ludmila Caproni , Forim Moacir Rossi , Pasqual Moacir , Dória Joyce
Published: October 2021

Garlic is a health promoter that has important bioactive compounds. The bioactive extraction is an important step in the analysis of constituents present in plant preparations. The purpose of this study is to optimize the extraction with the best proportion of solvents to obtain total phenolic compounds (TPC) and thiosulfinates (TS) from dried garlic powder, and evaluate the antioxidant activities of the optimized extracts. A statistical mixture simplex axial design was used to evaluate the effect of solvents (water, ethanol, and acetone), as well as mixtures of these solvents, after two ultrasound extraction cycles of 15 min. Results showed that solvent mixtures with a high portion of water and pure water were efficient for TPC and TS recovery through this extraction procedure. According to the regression model computed, the most significant solvent mixtures to obtain high TPC and TS recovery from dried garlic powder are, respectively, the binary mixture with 75% water and 25% acetone and pure water. These optimized extracts presented oxygen radical absorbance capacity. Pure water was better for total antioxidant capacity, and the binary mixture of water–acetone (75:25) was better for DPPH scavenging activity. These optimized extracts can be used for industrial and research applications.
Immunomodulatory Activities of Ammodytes personatus Egg Lipid in RAW264.7 Cells
Authors: Lim Jun Hyeok , Choi Gyoung Su , Monmai Chaiwat , Rod-in Weerawan , Jang A-yeong , Park Woo Jung
Published: October 2021

Ammodytes personatus, known as the Pacific sand lance, thrives in cold areas of the North Pacific. In this study, the total lipid was extracted from A. personatus eggs and the fatty acid composition was determined using gas chromatography (GC)–flame ionization detection (FID). The results showed that the extracted lipid contained high content of polyunsaturated fatty acids (PUFAs). The immunomodulatory activities of the A. personatus lipid were investigated using rodent macrophages. First, immune enhancement was analyzed, and the A. personatus lipid significantly and dose-dependently increased the NO production in RAW264.7 cells, and this lipid also regulated the transcription of immune-associated genes in RAW264.7 cells by activating the NF-κB and MAPK pathways. Additionally, flow cytometry revealed that this lipid stimulated phagocytosis. Conversely, the anti-inflammatory activity of the A. personatus lipid was also analyzed and the results showed significantly decreased NO production and gene expression in a dose-dependent manner in LPS-stimulated RAW264.7 cells. In addition, the A. personatus lipid suppressed the LPS-induced phosphorylation of proteins related to the NF-κB and MAPK pathways in LPS-stimulated RAW264.7 cells. Further, flow cytometry demonstrated the lipid-regulated anti-inflammatory activity via inhibition of CD86 expression. The results indicate that A. personatus egg lipid is a potential source of immunomodulation.
Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm
Authors: El-Hawari Lara , Bunjes Heike
Published: October 2021

Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc™) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc™ membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase.
Tandem Solid-Phase Extraction Columns for Simultaneous Aroma Extraction and Fractionation of Wuliangye and Other Baijiu
Authors: He Zhanglan , Yang Kangzhuo , Liu Zhipeng , An Mingzhe , Qiao Zongwei , Zhao Dong , Zheng Jia , Qian Michael
Published: October 2021

Wuliangye baijiu is one of the most famous baijiu in China, with a rich, harmonic aroma profile highly appreciated by consumers. Thousands of volatiles have been identified for the unique aroma profile. Among them, fatty acid esters have been identified as the main contributors to the aroma profile. In addition, many non-ester minor compounds, many of which are more polar than the esters, have been identified to contribute to the characteristic aroma unique to Wuliangye baijiu. The analysis of these minor compounds has been challenging due to the dominance of esters in the sample. Thus, it is desirable to fractionate the aroma extract into subgroups based on functional group or polarity to simplify the analysis. This study attempts a new approach to achieve simultaneous volatile extraction and fractionation using tandem LiChrolut EN and silica gel solid-phase extraction (SPE) columns. A baijiu sample (10 mL, diluted in 40 mL of water) was first passed through the LiChrolut EN (1.0 g) column. The loaded LiChrolut EN column was then dried with air and coupled with a silica gel (5.0 g) SPE column with anhydrous Na2SO4 (10.0 g) in between. The volatile compounds were eluted from the LiChrolut EN column and simultaneously fractionated on the silica gel column based on polarity. The simultaneous extraction and fractionation technique enabled the fractionations of all fatty acid esters into less polar fractions. Fatty acids, alcohols, pyrazines, furans, phenols, hydroxy esters, and other polar compounds were collected in more polar fractions. This technique was used to study the volatile compounds in Wuliangye, Moutai, and Fengjiu baijiu. In addition to fatty acid esters, many minor polar compounds, including 2,6-dimethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-3,5-dimethylpyrazine, p-cresol, and 2-acetylpyrrole, were unequivocally identified in the samples. The procedure is fast and straightforward, with low solvent consumption.
Integrated Network Pharmacology Analysis and In Vitro Validation Revealed the Potential Active Components and Underlying Mechanistic Pathways of Herba Patriniae in Colorectal Cancer
Authors: Yang Huihai , Cheung Man-Kit , Yue Grace Gar-Lee , Leung Ping-Chung , Wong Chun-Kwok , Lau Clara Bik-San
Published: October 2021

Herba Patriniae (HP) are medicinal plants commonly used in colorectal cancer (CRC) patients. In this study, network pharmacology was used to predict the active components and key signaling pathways of HP in CRC. Patrinia heterophylla, one type of HP, was chosen for validation of the network pharmacology analysis. The phytochemical profile of Patrinia heterophylla water extract (PHW) was determined by UHPLC-MS. MTT, RT-PCR, and Western blot assays were performed to evaluate the bioactivities of PHW in colon cancer cells. Results showed that 15 potentially active components of HP interacted with 28 putative targets of CRC in the compound–target network, of which asperglaucide had the highest degree. Furthermore, the ErbB signaling pathway was identified as the pathway mediated by HP with the most potential against CRC. Both RT-PCR and Western blot results showed that PHW significantly downregulated the mRNA and protein levels of EGFR, PI3K, and AKT in HCT116 cells. Asperglaucide, present in PHW, exhibited an anti-migratory effect in HCT116 cells, suggesting that it could be an active component of PHW in CRC treatment. In conclusion, this study has provided the first scientific evidence to support the use of PHW in CRC and paved the way for further research into the underlying mechanisms of PHW against CRC.
Synthesis of Indoloquinolines: An Intramolecular Cyclization Leading to Advanced Perophoramidine-Relevant Intermediates
Authors: Johnston Craig A. , Cordes David B. , Lebl Tomas , Slawin Alexandra M. Z. , Westwood Nicholas J.
Published: October 2021

The bioactive natural product perophoramidine has proved a challenging synthetic target. An alternative route to its indolo[2,3-b]quinolone core structure involving a N-chlorosuccinimde-mediated intramolecular cyclization reaction is reported. Attempts to progress towards the natural product are also discussed with an unexpected deep-seated rearrangement of the core structure occurring during an attempted iodoetherification reaction. X-ray crystallographic analysis provides important analytical confirmation of assigned structures.
Theoretical Analysis on Absorption of Carbon Dioxide (CO2) into Solutions of Phenyl Glycidyl Ether (PGE) Using Nonlinear Autoregressive Exogenous Neural Networks
Authors: Khan Naveed Ahmad , Sulaiman Muhammad , Tavera Romero Carlos Andrés , Alarfaj Fawaz Khaled
Published: October 2021

In this paper, we analyzed the mass transfer model with chemical reactions during the absorption of carbon dioxide (CO2) into phenyl glycidyl ether (PGE) solution. The mathematical model of the phenomenon is governed by a coupled nonlinear differential equation that corresponds to the reaction kinetics and diffusion. The system of differential equations is subjected to Dirichlet boundary conditions and a mixed set of Neumann and Dirichlet boundary conditions. Further, to calculate the concentration of CO2, PGE, and the flux in terms of reaction rate constants, we adopt the supervised learning strategy of a nonlinear autoregressive exogenous (NARX) neural network model with two activation functions (Log-sigmoid and Hyperbolic tangent). The reference data set for the possible outcomes of different scenarios based on variations in normalized parameters (α1, α2, β1, β2, k) are obtained using the MATLAB solver “pdex4”. The dataset is further interpreted by the Levenberg–Marquardt (LM) backpropagation algorithm for validation, testing, and training. The results obtained by the NARX-LM algorithm are compared with the Adomian decomposition method and residual method. The rapid convergence of solutions, smooth implementation, computational complexity, absolute errors, and statistics of the mean square error further validate the design scheme’s worth and efficiency.
Significantly Improved Colossal Dielectric Properties and Maxwell—Wagner Relaxation of TiO2—Rich Na1/2Y1/2Cu3Ti4+xO12 Ceramics
Authors: Saengvong Pariwat , Chanlek Narong , Putasaeng Bundit , Pengpad Atip , Harnchana Viyada , Krongsuk Sriprajak , Srepusharawoot Pornjuk , Thongbai Prasit
Published: October 2021

In this work, the colossal dielectric properties and Maxwell—Wagner relaxation of TiO2–rich Na1/2Y1/2Cu3Ti4+xO12 (x = 0–0.2) ceramics prepared by a solid-state reaction method are investigated. A single phase of Na1/2Y1/2Cu3Ti4O12 is achieved without the detection of any impurity phase. The highly dense microstructure is obtained, and the mean grain size is significantly reduced by a factor of 10 by increasing Ti molar ratio, resulting in an increased grain boundary density and hence grain boundary resistance (Rgb). The colossal permittivities of ε′ ~ 0.7–1.4 × 104 with slightly dependent on frequency in the frequency range of 102–106 Hz are obtained in the TiO2–rich Na1/2Y1/2Cu3Ti4+xO12 ceramics, while the dielectric loss tangent is reduced to tanδ ~ 0.016–0.020 at 1 kHz due to the increased Rgb. The semiconducting grain resistance (Rg) of the Na1/2Y1/2Cu3Ti4+xO12 ceramics increases with increasing x, corresponding to the decrease in Cu+/Cu2+ ratio. The nonlinear electrical properties of the TiO2–rich Na1/2Y1/2Cu3Ti4+xO12 ceramics can also be improved. The colossal dielectric and nonlinear electrical properties of the TiO2–rich Na1/2Y1/2Cu3Ti4+xO12 ceramics are explained by the Maxwell–Wagner relaxation model based on the formation of the Schottky barrier at the grain boundary.
Probing Electron Excitation Characters of Carboline-Based Bis-Tridentate Ir(III) Complexes
Authors: Yan Jie , Zhu Ze-Lin , Lee Chun-Sing , Liu Shih-Hung , Chou Pi-Tai , Chi Yun
Published: October 2021

In this work, we report a series of bis-tridentate Ir(III) metal complexes, comprising a dianionic pyrazole-pyridine-phenyl tridentate chelate and a monoanionic chelate bearing a peripheral carbene and carboline coordination fragment that is linked to the central phenyl group. All these Ir(III) complexes were synthesized with an efficient one-pot and two-step method, and their emission hue was fine-tuned by variation of the substituent at the central coordination entity (i.e., pyridinyl and phenyl group) of each of the tridentate chelates. Their photophysical and electrochemical properties, thermal stabilities and electroluminescence performances are examined and discussed comprehensively. The doped devices based on [Ir(cbF)(phyz1)] (Cb1) and [Ir(cbB)(phyz1)] (Cb4) give a maximum external quantum efficiency (current efficiency) of 16.6% (55.2 cd/A) and 13.9% (43.8 cd/A), respectively. The relatively high electroluminescence efficiencies indicate that bis-tridentate Ir(III) complexes are promising candidates for OLED applications.
Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
Authors: Gallien John , Srinageshwar Bhairavi , Gallo Kellie , Holtgrefe Gretchen , Koneru Sindhuja , Otero Paulina Sequeiros , Bueno Catalina Alvarez , Mosher Jamie , Roh Alison , Kohtz D. Stave , Swanson Douglas , Sharma Ajit , Dunbar Gary , Rossignol Julien
Published: October 2021

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH2), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH2) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
Development of HPLC Method for Catechins and Related Compounds Determination and Standardization in Miang (Traditional Lanna Fermented Tea Leaf in Northern Thailand)
Authors: Wangkarn Sunanta , Grudpan Kate , Khanongnuch Chartchai , Pattananandecha Thanawat , Apichai Sutasinee , Saenjum Chalermpong
Published: October 2021

High performance liquid chromatography (HPLC) for catechins and related compounds in Miang (traditional Lanna fermented tea leaf) was developed to overcome the matrices during the fermentation process. We investigated a variety of columns and elution conditions to determine seven catechins, namely (+)-catechin, (−)-gallocatechin, (−)-epigallocatechin, (−)-epicatechin, (−)-epigallocatechin gallate, (−)-gallocatechin gallate, (−)-epicatechin gallate, as well as gallic acid and caffeine, resulting in the development of reproducible systems for analyses that overcome sample matrices. Among the three reversed-phase columns, column C (deactivated, with extra dense bonding, double endcapped monomeric C18, high-purity silica at 3.0 mm × 250 mm and a 5 µm particle size) significantly improved the separation between Miang catechins in the presence of acid in the mobile phase within a shorter analysis time. The validation method showed effective linearity, precision, accuracy, and limits of detection and quantitation. The validated system was adequate for the qualitative and quantitative measurement of seven active catechins, including gallic acid and caffeine in Miang, during the fermentation process and standardization of Miang extracts. The latter contain catechins and related compounds that are further developed into natural active pharmaceutical ingredients (natural APIs) for cosmeceutical and nutraceutical products.
Occurrence of Phthalates in Bottled Drinks in the Chinese Market and Its Implications for Dietary Exposure
Authors: Xue Xiaohong , Su Yaoming , Su Hailei , Fan Dongping , Jia Hongliang , Chu Xiaoting , Song Xiaoyang , Liu Yuxian , Li Feilong , Xue Jingchuan , Liu Wenbin
Published: October 2021

Ubiquitous occurrences of phthalic acid esters (PAEs) or phthalates in a variety of consumer products have been demonstrated. Nevertheless, studies on their occurrence in various types of bottled drinks are limited. In this study, fifteen PAEs were analyzed in six categories of bottled drinks (n = 105) collected from the Chinese market, including mineral water, tea drinks, energy drinks, juice drinks, soft drinks, and beer. Among the 15 PAEs measured, DEHP was the most abundant phthalate with concentrations ranging from below the limit of quantification (LOQ) to 41,000 ng/L at a detection rate (DR) of 96%, followed by DIBP (DR: 88%) and DBP (DR: 84%) with respective concentration ranges of below LOQ to 16,000 and to 4900 ng/L. At least one PAE was detected in each drink sample, and the sum concentrations of 15 PAEs ranged from 770 to 48,004 ng/L (median: 6286 ng/L). Significant differences with respect to both PAE concentrations and composition profiles were observed between different types of bottled drinks. The median sum concentration of 15 PAEs in soft drinks was over five times higher than that detected in mineral water; different from other drink types. Besides DEHP, DBIP, and DBP, a high concentration of BMEP was also detected in a tea drink. The estimated daily dietary intake of phthalates (EDIdrink) through the consumption of bottled drinks was calculated based on the concentrations measured and the daily ingestion rates of bottled drink items. The EDIdrink values for DMP, DEP, DIBP, DBP, BMEP, DAP, BEEP, BBP, DCP, DHP, BMPP, BBEP, DEHP, DOP, and DNP through the consumption of bottled mineral water (based on mean concentrations) were 0.45, 0.33, 12.5, 3.67, 2.10, 0.06, 0.32, 0.16, 0.10, 0.09, 0.05, 0.81, 112, 0.13, and 0.20 ng/kg-bw/d, respectively, for Chinese adults. Overall, the EDIdrink values calculated for phthalates through the consumption of bottled drinks were below the oral reference doses suggested by the United States Environmental Protection Agency (U.S. EPA).
Control of the Induced Handedness of Helical Nanofilaments Employing Cholesteric Liquid Crystal Fields
Authors: Kim Ju-Yong , Lee Jae-Jin , Park Jun-Sung , Choi Yong-Jun , Choi Suk-Won
Published: October 2021

In this paper, a simple and powerful method to control the induced handedness of helical nanofilaments (HNFs) is presented. The nanofilaments are formed by achiral bent-core liquid crystal molecules employing a cholesteric liquid crystal field obtained by doping a rod-like nematogen with a chiral dopant. Homochiral helical nanofilaments are formed in the nanophase-separated helical nanofilament/cholesteric phase from a mixture with a cholesteric phase. This cholesteric phase forms at a temperature higher than the temperature at which the helical nanofilament in a bent-core molecule appears. Under such conditions, the cholesteric liquid crystal field acts as a driving force in the nucleation of HNFs, realizing a perfectly homochiral domain consisting of identical helical nanofilament handedness.
Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams
Authors: Christensen Søren Brøgger
Published: October 2021

The appearance of antibiotic drugs revolutionized the possibilities for treatment of diseases with high mortality such as pneumonia, sepsis, plaque, diphtheria, tetanus, typhoid fever, and tuberculosis. Today fewer than 1% of mortalities in high income countries are caused by diseases caused by bacteria. However, it should be recalled that the antibiotics were introduced in parallel with sanitation including sewerage, piped drinking water, high standard of living and improved understanding of the connection between food and health. Development of salvarsan, sulfonamides, and β-lactams into efficient drugs is described. The effects on life expectancy and life quality of these new drugs are indicated.
Effects of Surfactant Volume Fraction on the Antioxidant Efficiency and on The Interfacial Concentrations of Octyl and Tetradecyl p-Coumarates in Corn Oil-in-Water Emulsions
Authors: Costa Marlene , Losada-Barreiro Sonia , Paiva-Martins Fátima , Bravo-Díaz Carlos
Published: October 2021

Surfactants have been used for decades in the food industry for the preparation of lipid-based emulsified food stuffs. They play two main roles in the emulsification processes: first they decrease the interfacial tension between the oil and water, facilitating droplet deformation and rupture; second, they reduce droplet coalescence by forming steric barriers. However, addition of surfactants to binary oil-water mixtures also brings up the formation of three-dimensional interfacial layers, surrounding each emulsion droplet, that significantly alter chemical reactivity. This is the case, for instance, in the inhibition reaction between antioxidants and the lipid radicals formed in the course of the spontaneous oxidation reaction of unsaturated lipids, which are commonly employed in the preparation of food-grade emulsions. The rate of the inhibition reaction depends on the effective concentrations of antioxidants, which are mostly controlled by the amount of surfactant employed in the preparation of the emulsion. In this work, we analyze the effects of the surfactant Tween 20 on the oxidative stability and on the effective concentrations of two model antioxidants derived from cinnamic acid, determining their interfacial concentrations in the intact emulsions to avoid disrupting the existing equilibria and biasing results. For this purpose, a recently developed methodology was employed, and experimental results were interpreted on the grounds of a pseudophase kinetic model.
Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach
Authors: Verdino Anna , D’Urso Gaetano , Tammone Carmen , Scafuri Bernardina , Catapano Lucrezia , Marabotti Anna
Published: October 2021

Classic galactosemia is an inborn error of metabolism associated with mutations that impair the activity and the stability of galactose-1-phosphate uridylyltransferase (GALT), catalyzing the third step in galactose metabolism. To date, no treatments (including dietary galactose deprivation) are able to prevent or alleviate the long-term complications affecting galactosemic patients. Evidence that arginine is able to improve the activity of the human enzyme expressed in a prokaryotic model of classic galactosemia has induced researchers to suppose that this amino acid could act as a pharmacochaperone, but no effects were detected in four galactosemic patients treated with this amino acid. Given that no molecular characterizations of the possible effects of arginine on GALT have been performed, and given that the samples of patients treated with arginine are extremely limited for drawing definitive conclusions at the clinical level, we performed computational simulations in order to predict the interactions (if any) between this amino acid and the enzyme. Our results do not support the possibility that arginine could function as a pharmacochaperone for GALT, but information obtained by this study could be useful for identifying, in the future, possible pharmacochaperones for this enzyme.
HPTLC and ATR/FTIR Characterization of Antioxidants in Different Rosemary Extracts
Authors: Agatonovic-Kustrin Snezana , Balyklova Ksenia S. , Gegechkori Vladimir , Morton David W.
Published: October 2021

The effect of spontaneous fermentation by lactic acid bacteria on the extraction yield of bioactive compounds and antioxidant activity from rosemary leaf extracts was investigated using high-performance thin-layer chromatography (HPTLC). Brining and spontaneous fermentation with lactic acid bacteria more than doubled extraction of polyphenolics and antioxidants from the rosemary leaves. The results show that lactic acid fermentation enhances antioxidant activity in extracts by increasing the total phenolic content but does not increase extraction of phytosterols. Increased extraction of phenolic oxidants during fermentation assisted extraction, results from the in situ generated natural eutectic solvent from the plant sample. ATR-FTIR spectra from the bioactive bands suggests that this increased antioxidant activity is associated with increased extraction of rosmarinic acid, depolymerised lignin, abietane diterpenoids and 15-hydroxy-7-oxodehydroabietic acid.