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  • Phytochemical Screening and Antiprotozoal Effects of the Methanolic Berberis vulgaris and Acetonic Rhus coriaria Extracts
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Gaber El-Saber Batiha; Amany Magdy Beshbishy; Oluyomi Stephen Adeyemi; Eman Hassan Nadwa; Eman kadry Mohamed Rashwan; Luay M. Alkazmi; Amr A. Elkelish; Ikuo Igarashi

    Berberis vulgaris (B. vulgaris) and Rhus coriaria (R. coriaria) have been documented to have various pharmacologic activities. The current study assessed the in vitro as well as in vivo inhibitory efficacy of a methanolic extract of B. vulgaris (MEBV) and an acetone extract of R. coriaria (AERC) on six species of piroplasm parasites. The drug-exposure viability assay was tested on three different cell lines, namely mouse embryonic fibroblast (NIH/3T3), Madin-Darby bovine kidney (MDBK) and human foreskin fibroblast (HFF) cells. Qualitative phytochemical estimation revealed that both extracts containing alkaloid, tannin, saponins and terpenoids and significant amounts of flavonoids and polyphenols. The GC-MS analysis of MEBV and AERC revealed the existence of 27 and 20 phytochemical compounds, respectively. MEBV and AERC restricted the multiplication of Babesia (B.) bovis, B. bigemina, B. divergens, B. caballi, and Theileria (T.) equi at the half-maximal inhibitory concentration (IC50) of 0.84 ± 0.2, 0.81 ± 0.3, 4.1 ± 0.9, 0.35 ± 0.1 and 0.68 ± 0.1 µg/mL and 85.7 ± 3.1, 60 ± 8.5, 90 ± 3.7, 85.7 ± 2.1 and 78 ± 2.1 µg/mL, respectively. In the cytotoxicity assay, MEBV and AERC inhibited MDBK, NIH/3T3 and HFF cells with half-maximal effective concentrations (EC50) of 695.7 ± 24.9, 931 ± 44.9, ˃1500 µg/mL and 737.7 ± 17.4, ˃1500 and ˃1500 µg/mL, respectively. The experiments in mice showed that MEBV and AERC prohibited B. microti multiplication at 150 mg/kg by 66.7% and 70%, respectively. These results indicate the prospects of these extracts as drug candidates for piroplasmosis treatment following additional studies in some clinical cases.

    更新日期:2020-01-27
  • Adropin as A Fat-Burning Hormone with Multiple Functions—Review of a Decade of Research
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Mariami Jasaszwili; Maria Billert; Mathias Z. Strowski; Krzysztof W. Nowak; Marek Skrzypski

    Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. A decade after its discovery, there is evidence that adropin may contribute to body weight regulation, glucose and lipid homeostasis, and cardiovascular system functions. In this review, we summarize and discuss the physiological, metabolic, and pathophysiological factors regulating Enho as well as adropin. Furthermore, we review the literature addressing the role of adropin in adiposity and type 2 diabetes. Finally, we elaborate on the role of adropin in the context of the cardiovascular system, liver diseases, and cancer.

    更新日期:2020-01-27
  • Analysis of Binding Interactions of Ramipril and Quercetin on Human Serum Albumin: A Novel Method in Affinity Evaluation
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Zuzana Vaneková; Lukáš Hubčík; José Luis Toca-Herrera; Paul Georg Furtműller; Pavel Mučaji; Milan Nagy

    The aim of this study was to analyze the binding interactions between a common antihypertensive drug (ramipril, R) and the widely distributed plant flavonoid quercetin (Q), in the presence of human serum albumin (HSA). From the observed fluorescence spectra of the (HSA + R) system we can assume that ramipril is also one of the Site 3 ligands—similar to fusidic acid—the binding of which has been proven by RTG crystallography. Our claim is supported by near-UV CD spectroscopy, microscale themophoresis and molecular modeling. The presence of R slightly inhibited the subsequent binding of Q to HSA and, on the contrary, the pre-incubation of HSA with Q caused a stronger binding of R, most likely due to allosteric interactions. At high concentrations, R is also able to displace Q from its binding site. The dissociation constant KD for the binding of R is more than hundredfold larger than for Q, which means that R is a very weak binder to HSA. The knowledge of qualitative and quantitative parameters of R, as well as the methods used in this study, are important for future research into HSA binding. This study shows the importance of implementing other methods for KD determination. Microscale thermophoresis has proved to be a novel, practical and accurate method for KD determination on HSA, especially in cases when fluorescence spectroscopy is unable to produce usable results.

    更新日期:2020-01-27
  • Fine Modulation of the Catalytic Properties of Rhizomucor miehei Lipase Driven by Different Immobilization Strategies for the Selective Hydrolysis of Fish Oil
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Maryam Yousefi; Marzia Marciello; Jose Manuel Guisan; Gloria Fernandez-Lorente; Mehdi Mohammadi; Marco Filice

    Functional properties of each enzyme strictly depend on immobilization protocol used for linking enzyme and carrier. Different strategies were applied to prepare the immobilized derivatives of Rhizomucor miehei lipase (RML) and chemically aminated RML (NH2-RML). Both RML and NH2-RML forms were covalently immobilized on glyoxyl sepharose (Gx-RML and Gx-NH2-RML), glyoxyl sepharose dithiothreitol (Gx-DTT-RML and Gx-DTT-NH2-RML), activated sepharose with cyanogen bromide (CNBr-RML and CNBr-NH2-RML) and heterofunctional epoxy support partially modified with iminodiacetic acid (epoxy-IDA-RML and epoxy-IDA-NH2-RML). Immobilization varied from 11% up to 88% yields producing specific activities ranging from 0.5 up to 1.9 UI/mg. Great improvement in thermal stability for Gx-DTT-NH2-RML and epoxy-IDA-NH2-RML derivatives was obtained by retaining 49% and 37% of their initial activities at 70 °C, respectively. The regioselectivity of each derivative was also examined in hydrolysis of fish oil at three different conditions. All the derivatives were selective between cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) in favor of EPA. The highest selectivity (32.9 folds) was observed for epoxy-IDA-NH2-RML derivative in the hydrolysis reaction performed at pH 5 and 4 °C. Recyclability study showed good capability of the immobilized biocatalysts to be used repeatedly, retaining 50%–91% of their initial activities after five cycles of the reaction.

    更新日期:2020-01-27
  • Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Eman Assirey; Azhaar Alsaggaf; Arshi Naqvi; Ziad Moussa; Rawda M. Okasha; Tarek H. Afifi; Alaa S. Abd-El-Aziz

    Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

    更新日期:2020-01-27
  • Photolysis of 5-Azido-3-Phenylisoxazole at Cryogenic Temperature: Formation and Direct Detection of a Nitrosoalkene
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Upasana Banerjee; William L. Karney; Bruce S. Ault; Anna D. Gudmundsdottir

    To enhance the versatility of organic azides in organic synthesis, a better understanding of their photochemistry is required. Herein, the photoreactivity of azidoisoxazole 1 was characterized in cryogenic matrices with IR and UV-Vis absorption spectroscopy. The irradiation (λ = 254 nm) of azidoisoxazole 1 in an argon matrix at 13 K and in glassy 2-methyltetrahydrofuran (mTHF) at 77 K yielded nitrosoalkene 3. Density functional theory (DFT) and complete active space self-consistent field (CASSCF) calculations were used to aid the characterization of nitrosoalkene 3 and to support the proposed mechanism for its formation. It is likely that nitrosoalkene 3 is formed from the singlet excited state of azidoisoxazole 1 via a concerted mechanism or from cleavage of an intermediate singlet nitrene that does not undergo efficient intersystem crossing to its triplet configuration.

    更新日期:2020-01-27
  • Novel Cationic Prodrug of Ubiquinol-10 Enhances Intestinal Absorption via Efficient Formation of Nanosized Mixed-Micelles with Bile Acid Anions
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Shuichi Setoguchi; Ryoji Hidaka; Nami Nagata-Akaho; Daisuke Watase; Mitsuhisa Koga; Kazuhisa Matsunaga; Yoshiharu Karube; Jiro Takata

    The aim of this study was to develop a prodrug of ubiquinol-10 (UqH-10), the active form of ubiquinone-10 (Uq-10), for oral delivery. Bioavailability of UqH-10 is hampered by its high susceptibility to oxidation and water-insolubility. We prepared three novel N,N-dimethylglycine ester derivatives of UqH-10, including a 1-monoester (UqH-1-DMG), 4-monoester (UqH-4-DMG), and 1,4-bis-ester (UqH-DMG), and assessed their physicochemical properties in vitro and in vivo. UqH-DMG spontaneously formed an aqueous micelle solution comprising 20 nm particles at 36.5 °C. Cationic UqH-DMG formed nano-sized (5 nm) mixed-micelles with taurocholic acid. Reconversion of the derivatives to UqH-10 was accelerated in human liver microsomes. The oral bioavailability of UqH-10 after administration of UqH-derivatives or Uq-10 was determined in fasted and postprandial rats secreting normal and high levels of bile, respectively. In fasted rats, plasma UqH-10 after UqH-derivatives administration reached Cmax at 2–3 h and after Uq-10 administration, it remained low. The AUC0-24h of UqH-10 after UqH-derivatives administration was 2–3-fold higher than that after Uq-10 administration. In postprandial rats, the Tmax of UqH-10 after UqH-derivatives administration was an hour earlier than after Uq-10 administration. In conclusion, cationic UqH-derivatives are convenient prodrugs that enhance UqH-10 bioavailability by forming nanosized mixed-micelles with intestinal bile acids.

    更新日期:2020-01-27
  • Advances in Synthesis of π-Extended Benzosilole Derivatives and Their Analogs
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Tuan Thanh Dang; Hue Minh Thi Nguyen; Hien Nguyen; Tran Ngoc Dung; Minh Tho Nguyen; Wim Dehaen

    Benzosiloles and their π-extended derivatives are present in many important advanced materials due to their excellent physical properties. Especially, they have found many potential applications in the development of novel electronic materials such as OLEDs, semiconductors and solar cells. In this review, we have summarized several main approaches to construct (di)benzosilole derivatives and (benzo)siloles fused to aromatic five- and six-membered heterocycles.

    更新日期:2020-01-27
  • Yellow Emission Obtained by Combination of Broadband Emission and Multi-Peak Emission in Garnet Structure Na2YMg2V3O12: Dy3+ Phosphor
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Weiyi Zhang; Can He; Xiaowen Wu; Ximing Huang; Fankai Lin; Yan’gai Liu; Minghao Fang; Xin Min; Zhaohui Huang

    The fabrication and luminescent performance of novel phosphors Na2YMg2V3O12:Dy3+ were investigated by a conventional solid-state reaction method. Under near-UV light, the Na2YMg2V3O12 host self-activated and released a broad emission band (400–700 nm, with a peak at 524 nm) ascribable to charge transfer in the (VO4)3− groups. Meanwhile, the Na2YMg2V3O12:Dy3+ phosphors emitted bright yellow light within both the broad emission band of the (VO4)3- groups and the sharp peaks of the Dy3+ ions at 490, 582, and 663 nm at a quenching concentration of 0.03 mol. The emission of the as-prepared Na2YMg2V3O12:Dy3+ phosphors remained stable at high temperatures. The obtained phosphors, commercial Y2O3:Eu3+ red phosphors, and BaMgAl10O17:Eu2+ blue phosphors were packed into a white light-emitting diode (WLED) device with a near-UV chip. The designed WLED emitted bright white light with good chromaticity coordinates (0.331, 0.361), satisfactory color rendering index (80.2), and proper correlation to a color temperature (7364 K). These results indicate the potential utility of Na2YMg2V3O12:Dy3+ phosphor as a yellow-emitting phosphor in solid-state illumination.

    更新日期:2020-01-27
  • Production of 5-Hydroxymethylfurfural from Chitin Biomass: A Review
    Molecules (IF 3.060) Pub Date : 2020-01-27
    Dan Zhou; Dongsheng Shen; Wenjing Lu; Tao Song; Meizhen Wang; Huajun Feng; Jiali Shentu; Yuyang Long

    Chitin biomass, a rich renewable resource, is the second most abundant natural polysaccharide after cellulose. Conversion of chitin biomass to high value-added chemicals can play a significant role in alleviating the global energy crisis and environmental pollution. In this review, the recent achievements in converting chitin biomass to high-value chemicals, such as 5-hydroxymethylfurfural (HMF), under different conditions using chitin, chitosan, glucosamine, and N-acetylglucosamine as raw materials are summarized. Related research on pretreatment technology of chitin biomass is also discussed. New approaches for transformation of chitin biomass to HMF are also proposed. This review promotes the development of industrial technologies for degradation of chitin biomass and preparation of HMF. It also provides insight into a sustainable future in terms of renewable resources.

    更新日期:2020-01-27
  • The Role of Salicylic Acid in Plants Exposed to Heavy Metals
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Anket Sharma; Gagan Preet Singh Sidhu; Fabrizio Araniti; Aditi Shreeya Bali; Babar Shahzad; Durgesh Kumar Tripathi; Marian Brestic; Milan Skalicky; Marco Landi

    Salicylic acid (SA) is a very simple phenolic compound (a C7H6O3 compound composed of an aromatic ring, one carboxylic and a hydroxyl group) and this simplicity contrasts with its high versatility and the involvement of SA in several plant processes either in optimal conditions or in plants facing environmental cues, including heavy metal (HM) stress. Nowadays, a huge body of evidence has unveiled that SA plays a pivotal role as plant growth regulator and influences intra- and inter-plant communication attributable to its methyl ester form, methyl salicylate, which is highly volatile. Under stress, including HM stress, SA interacts with other plant hormones (e.g., auxins, abscisic acid, gibberellin) and promotes the stimulation of antioxidant compounds and enzymes thereby alerting HM-treated plants and helping in counteracting HM stress. The present literature survey reviews recent literature concerning the roles of SA in plants suffering from HM stress with the aim of providing a comprehensive picture about SA and HM, in order to orientate the direction of future research on this topic.

    更新日期:2020-01-26
  • TBAB-Catalyzed 1,6-Conjugate Sulfonylation of para-Quinone Methides: A Highly Efficient Approach to Unsymmetrical gem-Diarylmethyl Sulfones in Water
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Zhang-Qin Liu; Peng-Sheng You; Liang-Dong Zhang; Da-Qing Liu; Sheng-Shu Liu; Xiao-Yu Guan

    A highly efficient sulfonylation of para-quinone methides with sulfonyl hydrazines in water has been developed on the basis of the mode involving a tetrabutyl ammonium bromide (TBAB)-promoted sulfa-1,6-conjugated addition pathway. This reaction provides a green and sustainable method to synthesize various unsymmetrical diarylmethyl sulfones, showing good functional group tolerance, scalability, and regioselectivity. Further transformation of the resulting diarylmethyl sulfones provides an efficient route to some functionalized molecules.

    更新日期:2020-01-26
  • Apoptotic Effects on HL60 Human Leukaemia Cells Induced by Lavandin Essential Oil Treatment
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Valentina Laghezza Masci; Elisa Ovidi; Anna Rita Taddei; Giovanni Turchetti; Antonio Tiezzi; Pierluigi Giacomello; Stefania Garzoli

    Recent scientific investigations have reported a number of essential oils to interfere with intracellular signalling pathways and to induce apoptosis in different cancer cell types. In this paper, Lavandin Essential Oil (LEO), a natural sterile hybrid obtained by cross-breeding L. angustifolia × L. latifolia, was tested on human leukaemia cells (HL60). Based on the MTT results, the reduced cell viability of HL60 cells was further investigated to determine whether cell death was related to the apoptotic process. HL60 cells treated for 24 h with LEO were processed by flow cytometry, and the presence of Annexin V was measured. The activation of caspases-3 was evaluated by western blot and immunofluorescence techniques. Treated cells were also examined by scanning and transmission electron microscopy to establish the possible occurrence of morphological alterations during the apoptotic process. LEO main compounds, such as linalool, linalyl acetate, 1,8-cineole, and terpinen-4-ol, were also investigated by MTT and flow cytometry analysis. The set of obtained results showed that LEO treatments induced apoptosis in a dose-dependent, but not time-dependent, manner on HL60 cells, while among LEO main compounds, both terpinen-4-ol and linalyl acetate were able to induce apoptosis.

    更新日期:2020-01-26
  • Overcoming Resistance to Platinum-Based Drugs in Ovarian Cancer by Salinomycin and Its Derivatives—An In Vitro Study
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Marcin Michalak; Michał Stefan Lach; Michał Antoszczak; Adam Huczyński; Wiktoria Maria Suchorska

    Polyether ionophore salinomycin (SAL) and its semi-synthetic derivatives are recognized as very promising anticancer drug candidates due to their activity against various types of cancer cells, including multidrug-resistant populations. Ovarian cancer is the deadliest among gynecologic malignancies, which is connected with the development of chemoresistant forms of the disease in over 70% of patients after initial treatment regimen. Thus, we decided to examine the anticancer properties of SAL and selected SAL derivatives against a series of drug-sensitive (A2780, SK-OV-3) and derived drug-resistant (A2780 CDDP, SK-OV-3 CDDP) ovarian cancer cell lines. Although SAL analogs showed less promising IC50 values than SAL, they were identified as the antitumor agents that significantly overcome the resistance to platinum-based drugs in ovarian cancer, more potent than unmodified SAL and commonly used anticancer drugs—5-fluorouracil, gemcitabine, and cisplatin. Moreover, when compared with SAL used alone, our experiments proved for the first time increased selectivity of SAL-based dual therapy with 5-fluorouracil or gemcitabine, especially towards A2780 cell line. Looking closer at the results, SAL acted synergistically with 5-fluorouracil towards the drug-resistant A2780 cell line. Our results suggest that combinations of SAL with other antineoplastics may become a new therapeutic option for patients with ovarian cancer.

    更新日期:2020-01-26
  • Deep Oxidative Desulfurization of Fuels in the Presence of Brönsted Acidic Polyoxometalate-Based Ionic Liquids
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Argam Akopyan; Ekaterina Eseva; Polina Polikarpova; Anastasia Kedalo; Anna Vutolkina; Aleksandr Glotov

    Polyoxometalate-based ionic liquid hybrid materials with a pyridinium cation, containing Brönsted acid sites, were synthesized and used as catalysts for the oxidation of model and real diesel fuels. Keggin-type polyoxometalates with the formulae [PMo12O40]3−, [PVMo11O40]4−, [PV2Mo10O40]4−, [PW12O40]3− were used as anions. It was shown that increasing the acid site strength leads to an increase of dibenzothiophene conversion to the corresponding sulfone. The best results were obtained in the presence of a catalyst, containing a nicotinic acid derivative as cation and phosphomolybdate as anion. The main factors affecting the process consisting of catalyst dosage, temperature, reaction time, oxidant dosage were investigated in detail. Under optimal conditions full oxidation of dibenzothiophene and more than a 90% desulfurization degree of real diesel fuel (initial sulfur content of 2050 ppm) were obtained (the oxidation conditions: NK-1 catalyst, molar ratio H2O2:S 10:1, molar ratio S:Mo 8:1, 1 mL MeCN, 70 °C, 1 h). The synthesized catalysts could be used five times with a slight decrease in activity.

    更新日期:2020-01-26
  • Pharmacokinetic Characterization and Tissue Distribution of Fusion Protein Therapeutics by Orthogonal Bioanalytical Assays and Minimal PBPK Modeling
    Molecules (IF 3.060) Pub Date : 2020-01-26
    Hiroshi Sugimoto; Susan Chen; Mark G. Qian

    Characterization of pharmacokinetic (PK) properties and target tissue distribution of therapeutic fusion proteins (TFPs) are critical in supporting in vivo efficacy. We evaluated the pharmacokinetic profile of an investigational TFP consisting of human immunoglobulin G4 fused to the modified interferon alpha by orthogonal bioanalytical assays and applied minimal physiologically based pharmacokinetic (PBPK) modeling to characterize the TFP pharmacokinetics in mouse. The conventional ligand binding assay (LBA), immunocapture-liquid chromatography/tandem mass spectrometry (IC-LC/MS) detecting the human IgG4 peptide or the interferon alpha peptide were developed to measure the TFP concentrations in mouse plasma and tumor. The minimal PBPK model incorporated a tumor compartment model was used for data fitting. The plasma clearance measured by LBA and IC-LC/MS was comparable in the range of 0.5–0.6 mL/h/kg. However, the tumor exposure measured by the generic human IgG4 IC-LC/MS was significantly underestimated compared with the interferon alpha specific IC-LC/MS and LBA. Furthermore, the minimal PBPK model simultaneously captured the relationship between plasma and tissue exposure. We proposed the streamlined practical strategy to characterize the plasma exposure and tumor distribution of a TFP by both LBA and IC-LC/MS. The minimal PBPK modeling was established for better understanding of pharmacokinetic profile of investigational TFPs in the biotherapeutic discovery.

    更新日期:2020-01-26
  • Characterization of Isolated Extracts from Justicia Plant Leaves used as Remedy for Anemia
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Jana Wood; Sayeda Yasmin-Karim; Michele Moreau; Rajiv Kumar; Janet Akwanwi; Atoh Derek; Fred Atoneche; John Kress; and Wilfred Ngwa

    Indigenous populations use plants as an important healthcare resource or remedy for different diseases. Here, isolated extracts from Justicia (family Acanthanceae) plant leaves used in Africa as remedy for anemia are characterized by different methods to assess composition and potential nutritional or therapeutic value. Extracts from Justicia leaves were obtained by aqueous extraction, with further isolation by centrifuging and high-performance liquid chromatography. Extracts and isolated compounds were characterized by ultraviolet–visible (UV-Vis) spectroscopy and inductively coupled plasma mass spectrometry (ICP-MS). Hemoglobin activity was assessed using different hemoglobin assays (Cayman Chemical, and Sigma–Aldrich), as well as ELISA. In addition, the safety of the isolated samples was assessed in vitro and in vivo in mice. ICP-MS study results revealed many essential metabolites found in blood plasma. The UV-Vis spectroscopy results highlighted the presence of hemoglobin, with assays showing levels over 4 times higher than that of similar mass of lyophilized human hemoglobin. Meanwhile, in vivo studies showed faster recovery from anemia in mice administered with the isolated extracts compared to untreated mice. Moreover, in vitro and in vivo studies highlighted safety of the extracts. This study reveals the presence of high levels of elements essential for blood health in the isolated extracts from Justicia plant leaves. The findings inspire further research with the potential applications in food fortification, and as remedy for blood disorders like anemia, which disproportionally affects cancer patients, pregnant women, and populations in low- and middle-income countries.

    更新日期:2020-01-26
  • Chlorpyrifos Oxon-Induced Isopeptide Bond Formation in Human Butyrylcholinesterase
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Kevser Biberoglu; Ozden Tacal; Lawrence M. Schopfer; Oksana Lockridge

    A newly recognized action of organophosphates (OP) is the ability to crosslink proteins through an isopeptide bond. The first step in the mechanism is covalent addition of the OP to the side chain of lysine. This activates OP-lysine for reaction with a nearby glutamic or aspartic acid to make a gamma glutamyl epsilon lysine bond. Crosslinked proteins are high molecular weight aggregates. Our goal was to identify the residues in the human butyrylcholinesterase (HuBChE) tetramer that were crosslinked following treatment with 1.5 mM chlorpyrifos oxon. High molecular weight bands were visualized on an SDS gel. Proteins in the gel bands were digested with trypsin, separated by liquid chromatography and analyzed in an Orbitrap mass spectrometer. MSMS files were searched for crosslinked peptides using the Batch-Tag program in Protein Prospector. MSMS spectra were manually evaluated for the presence of ions that supported the crosslinks. The crosslink between Lys544 in VLEMTGNIDEAEWEWK544AGFHR and Glu542 in VLEMTGNIDEAEWE542WK satisfied our criteria including that of spatial proximity. Distances between Lys544 and Glu542 were 7.4 and 9.5 Å, calculated from the cryo-EM (electron microscopy) structure of the HuBChE tetramer. Paraoxon ethyl, diazoxon, and dichlorvos had less pronounced effects as visualized on SDS gels. Our proof-of-principle study provides evidence that OP have the ability to crosslink proteins. If OP-induced protein crosslinking occurs in the brain, OP exposure could be responsible for some cases of neurodegenerative disease.

    更新日期:2020-01-26
  • Substituted Piperazines as Novel Potential Radioprotective Agents
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Alzbeta Filipova; Jan Marek; Radim Havelek; Jaroslav Pejchal; Marcela Jelicova; Jana Cizkova; Martina Majorosova; Lubica Muckova; Tomas Kucera; Lukas Prchal; Miroslav Psotka; Natalie Zivna; Darja Koutova; Zuzana Sinkorova; Martina Rezacova; Ales Tichy

    The increasing risk of radiation exposure underlines the need for novel radioprotective agents. Hence, a series of novel 1-(2-hydroxyethyl)piperazine derivatives were designed and synthesized. Some of the compounds protected human cells against radiation-induced apoptosis and exhibited low cytotoxicity. Compared to the previous series of piperazine derivatives, compound 8 exhibited a radioprotective effect on cell survival in vitro and low toxicity in vivo. It also enhanced the survival of mice 30 days after whole-body irradiation (although this increase was not statistically significant). Taken together, our in vitro and in vivo data indicate that some of our compounds are valuable for further research as potential radioprotectors.

    更新日期:2020-01-26
  • Theoretical Description of R–X⋯NH3 Halogen Bond Complexes: Effect of the R Group on the Complex Stability and Sigma-Hole Electron Depletion
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Juan Zurita; Vladimir Rodriguez; Cesar Zambrano; Jose Ramón Mora; Luis Rincón; F. Javier Torres

    In the present work, a number of R–X⋯NH3 (X = Cl, Br, and I) halogen bonded systems were theoretical studied by means of DFT calculations performed at the ωB97XD/6-31+G(d,p) level of theory in order to get insights on the effect of the electron-donating or electron-withdrawing character of the different R substituent groups (R = halogen, methyl, partially fluorinated methyl, perfluoro-methyl, ethyl, vinyl, and acetyl) on the stability of the halogen bond. The results indicate that the relative stability of the halogen bond follows the Cl < Br < I trend considering the same R substituent whereas the more electron-withdrawing character of the R substituent the more stable the halogen bond. Refinement of the latter results, performed at the MP2/6-31+G(d,p) level showed that the DFT and the MP2 binding energies correlate remarkably well, suggesting that the Grimme’s type dispersion-corrected functional produces reasonable structural and energetic features of halogen bond systems. DFT results were also observed to agree with more refined calculations performed at the CCSD(T) level. In a further stage, a more thorough analysis of the R–Br⋯NH3 complexes was performed by means of a novel electron localization/delocalization tool, defined in terms of an Information Theory, IT, based quantity obtained from the conditional pair density. For the latter, our in-house developed C++/CUDA program, called KLD (acronym of Kullback–Leibler divergence), was employed. KLD results mapped onto the one-electron density plotted at a 0.04 a.u. isovalue, showed that (i) as expected, the localized electron depletion of the Br sigma-hole is largely affected by the electron-withdrawing character of the R substituent group and (ii) the R–X bond is significantly polarized due to the presence of the NH3 molecule in the complexes. The afore-mentioned constitutes a clear indication of the dominant character of electrostatics on the stabilization of halogen bonds in agreement with a number of studies reported in the main literature. Finally, the cooperative effects on the [Br—CN]n system (n = 1–8) was evaluated at the MP2/6-31+G(d,p) level, where it was observed that an increase of about ~14.2% on the complex stability is obtained when going from n = 2 to n = 8. The latter results were corroborated by the analysis of the changes on the Fermi-hole localization pattern on the halogen bond zones, which suggests an also important contribution of the electron correlation in the stabilization of these systems.

    更新日期:2020-01-26
  • Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Yoo-Seong Jeong; Minjeong Baek; Seungbeom Lee; Min-Soo Kim; Han-Joo Maeng; Jong-Hwa Lee; Young-Ger Suh; Suk-Jae Chung

    SH-1242, a novel inhibitor of heat shock protein 90 (HSP90), is a synthetic analog of deguelin: It was previously reported that the treatment of SH-1242 led to a strong suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the hypoxia-induced upregulation of expression in hypoxia-inducible factor 1α (HIF-1ɑ) and vascular endothelial growth factor (VEGF). In this study, an analytical method for the quantification of SH-1242 in biological samples from rats and mice was developed/validated for application in pharmacokinetic studies. SH-1242 and deguelin, an internal standard of the assay, in plasma samples from the rodents were extracted with methanol containing 0.1% formic acid and analyzed at m/z transition values of 368.9→151.0 and 395.0→213.0, respectively. The method was validated in terms of accuracy, precision, dilution, matrix effects, recovery, and stability and shown to comply with validation guidelines when it was used in the concentration ranges of 1–1000 ng/mL for rat plasma and of 2–1000 ng/mL for mouse plasma. SH-1242 levels in plasma samples were readily determined using the developed method for up to 480 min after the intravenous administration of 0.1 mg/kg SH-1242 to rats and for up to 120 min to mice. These findings suggested that the current method was practical and reliable for pharmacokinetic studies on SH-1242 in preclinical animal species.

    更新日期:2020-01-26
  • Aspidoptoids A–D: Four New Diterpenoids from Aspidopterys obcordata Vine
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Peng Sun; Dong-Hua Cao; Yi-Dian Xiao; Zong-Yi Zhang; Jia-Nan Wang; Xiao-Cui Shi; Chun-Fen Xiao; Hua-Bin Hu; You-Kai Xu

    Four new diterpenoids, named aspidoptoids A–D (1–4), together with two known analogues (5–6) were isolated from Aspidopterys obcordata vine. Aspidoptoids A–B (1–2) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B (2) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production.

    更新日期:2020-01-26
  • Microbial Transformation of Prenylquercetins by Mucor hiemalis
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Fubo Han; Yina Xiao; Ik-Soo Lee

    Quercetin, one of the most widely distributed flavonoids, has been found to show various biological activities including antioxidant, anticancer, and anti-inflammatory effects. It has been reported that bioactivity enhancement of flavonoids has often been closely associated with nuclear prenylation, as shown in 8-prenylquercetin and 5′-prenylquercetin. It has also been revealed in many studies that the biological activities of flavonoids could be improved after glucosylation. Three prenylated quercetins were prepared in this study, and microbial transformation was carried out in order to identify derivatives of prenylquercetins with increased water solubility and improved bioavailability. The fungus M. hiemalis was proved to be capable of converting prenylquercetins into more polar metabolites and was selected for preparative fermentation. Six novel glucosylated metabolites were obtained and their chemical structures were elucidated by NMR and mass spectrometric analyses. All the microbial metabolites showed improvement in water solubility.

    更新日期:2020-01-26
  • Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Cristina Maria Al Matarneh; Roxana Maria Amarandi; Anda Mihaela Craciun; Ionel I. Mangalagiu; Gheorghita Zbancioc; Ramona Danac

    Three series of fused pyrrolophenanthroline derivatives were designed as analogues of phenstatin and synthesized in two steps starting with 1,7-phenanthroline, 4,7-phenanthroline and 1,10-phenanthroline, respectively. Two (Compounds 8a and 11c) of the four compounds tested against a panel of sixty human cancer cell lines of the National Cancer Institute (NCI) exhibited significant growth inhibition activity on several cell lines. Compound 11c showed a broad spectrum in terms of antiproliferative efficacy with GI50 values in the range of 0.296 to 250 μM. Molecular docking studies indicated that Compounds 8a and 11c are accommodated in the colchicine binding site of tubulin in two different ways.

    更新日期:2020-01-26
  • Industrial Application of Nanocelluloses in Papermaking: A Review of Challenges, Technical Solutions, and Market Perspectives
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Ana Balea; Elena Fuente; M. Concepcion Monte; Noemi Merayo; Cristina Campano; Carlos Negro; Angeles Blanco

    Nanocelluloses (NC) increase mechanical and barrier paper properties allowing the use of paper in applications actually covered by other materials. Despite the exponential increase of information, NC have not been fully implemented in papermaking yet, due to the challenges of using NC. This paper provides a review of the main new findings and emerging possibilities in this field by focusing mainly on: (i) Decoupling the effects of NC on wet-end and paper properties by using synergies with retention aids, chemical modification, or filler preflocculation; (ii) challenges and solutions related to the incorporation of NC in the pulp suspension and its effects on barrier properties; and (iii) characterization needs of NC at an industrial scale. The paper also includes the market perspectives. It is concluded that to solve these challenges specific solutions are required for each paper product and process, being the wet-end optimization the key to decouple NC effects on drainage and paper properties. Furthermore, the effect of NC on recyclability must also be taken into account to reach a compromise solution. This review helps readers find upscale options for using NC in papermaking and identify further research needs within this field.

    更新日期:2020-01-26
  • Structural Diversity of Sense and Antisense RNA Hexanucleotide Repeats Associated with ALS and FTLD
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Tim Božič; Matja Zalar; Boris Rogelj; Janez Plavec; Primož Šket

    The hexanucleotide expansion GGGGCC located in C9orf72 gene represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Since the discovery one of the non-exclusive mechanisms of expanded hexanucleotide G4C2 repeats involved in ALS and FTLD is RNA toxicity, which involves accumulation of pathological sense and antisense RNA transcripts. Formed RNA foci sequester RNA-binding proteins, causing their mislocalization and, thus, diminishing their biological function. Therefore, structures adopted by pathological RNA transcripts could have a key role in pathogenesis of ALS and FTLD. Utilizing NMR spectroscopy and complementary methods, we examined structures adopted by both guanine-rich sense and cytosine-rich antisense RNA oligonucleotides with four hexanucleotide repeats. While both oligonucleotides tend to form dimers and hairpins, the equilibrium of these structures differs with antisense oligonucleotide being more sensitive to changes in pH and sense oligonucleotide to temperature. In the presence of K+ ions, guanine-rich sense RNA oligonucleotide also adopts secondary structures called G-quadruplexes. Here, we also observed, for the first time, that antisense RNA oligonucleotide forms i-motifs under specific conditions. Moreover, simultaneous presence of sense and antisense RNA oligonucleotides promotes formation of heterodimer. Studied structural diversity of sense and antisense RNA transcripts not only further depicts the complex nature of neurodegenerative diseases but also reveals potential targets for drug design in treatment of ALS and FTLD.

    更新日期:2020-01-26
  • Alkoxy- and Silanol-Functionalized Cage-Type Oligosiloxanes as Molecular Building Blocks to Construct Nanoporous Materials
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Atsushi Shimojima; Kazuyuki Kuroda

    Siloxane-based materials have a wide range of applications. Cage-type oligosiloxanes have attracted significant attention as molecular building blocks to construct novel siloxane-based nanoporous materials with promising applications such as in catalysis and adsorption. This paper reviews recent progress in the preparation of siloxane-based nanoporous materials using alkoxy- and silanol-functionalized cage siloxanes. The arrangement of cage siloxanes units is controlled by various methods, including amphiphilic self-assembly, hydrogen bonding of silanol groups, and regioselective functionalization, toward the preparation of ordered nanoporous siloxane-based materials.

    更新日期:2020-01-26
  • Dual Emission in a Ligand and Metal Co-Doped Lanthanide-Organic Framework: Color Tuning and Temperature Dependent Luminescence
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Despoina Andriotou; Stavros A. Diamantis; Anna Zacharia; Grigorios Itskos; Nikos Panagiotou; Anastasios J. Tasiopoulos; Theodore Lazarides

    In this study, we report the luminescence color tuning in the lanthanide metal-organic framework (LnMOF) ([La(bpdc)Cl(DMF)] (1); bpdc2− = [1,1′-biphenyl]-4,4′-dicarboxylate, DMF = N,N-dimethylformamide) by introducing dual emission properties in a La3+ MOF scaffold through doping with the blue fluorescent 2,2′-diamino-[1,1′-biphenyl]-4,4′-dicarboxylate (dabpdc2−) and the red emissive Eu3+. With a careful adjustment of the relative doping levels of the lanthanide ions and bridging ligands, the color of the luminescence was modulated, while at the same time the photophysical characteristics of the two chromophores were retained. In addition, the photophysical properties of the parent MOF (1) and its doped counterparts with various dabpdc2−/bpdc2− and Eu3+/La3+ ratios and the photoinduced energy transfer pathways that are possible within these materials are discussed. Finally, the temperature dependence study on the emission profile of a doped analogue containing 10% dabpdc2− and 2.5% Eu3+ (7) is presented, highlighting the potential of this family of materials to behave as temperature sensors.

    更新日期:2020-01-26
  • Comparative Study of the Effect of 5,6-Dihydroergosterol and 3-epi-5,6-dihydroergosterol on Chemokine Expression in Human Keratinocytes
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Ye Seul Park; Hye Jin Moon; Kwang Hyun Ahn; Tae Hoon Lee; Hakwon Kim

    5,6-Dihydroergosterol-glucose is an organic synthetic derivative of spinasterol-glucose, which has potent anti-inflammatory activity. We previously synthesized alpha and beta anomers of DHE-glycosides and compared their inhibitory activity on CCL17 and CCL22 mRNA expression induced by TNF-α/IFN-γ in activated HaCaTs. Recently, we synthesized a new type of DHE-glycosides, 3-epi-5,6-dihydroergosterol(3-epi-DHE)-glycosides, and compared its inhibitory activity on mRNA expression levels of CCL17 and CCL22 in TNF-α/IFN-γ-induced HaCaT. DHE-Xly did not affect TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression in HaCaTs, however, 3-epi-DHE-Xly strongly inhibited TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression levels in human keratinocytes. These results provide important clues for development of chronic dermatitis treatment via inhibition of chemokine expression using DHE derivatives.

    更新日期:2020-01-26
  • Finger-Temperature-Detecting Liquid Crystal Composite Film for Anti-Counterfeiting Labels
    Molecules (IF 3.060) Pub Date : 2020-01-25
    Yanzi Gao; Ke Feng; Jin Zhang; Lanying Zhang

    The development of the economy has increased the demand for anti-counterfeiting technologies, and with the traditional ones becoming known to the public, new and more effective ones are needed. In this study, a series of liquid crystal mixtures containing side-chain liquid crystal polymers and small-molecular-weight liquid crystals (LCs) were designed and prepared. The phase transition behavior and self-assembling structures of the LC mixtures were investigated by a combination of differential scanning calorimetry, polarized optical microscopy, and small-angle X-ray diffraction. The optical properties of the mixture film were characterized with a UV/VIS/IR spectrum study. The results reveal that the obtained film exhibited different optical modes between transparent, scattering, and selective reflection under finger-temperature control. Therefore, by the introduction of a coexisting thermal- or optical-polymer-dispersed network, a liquid crystal composite film with an integration of apparent optical switching modes and enhanced strength and toughness was successfully demonstrated. This research provides a versatile strategy for the design and preparation of liquid crystal anti-counterfeiting materials for practical use. In this study, a prototype finger-temperature-detecting anti-counterfeiting label was prepared, and its temperature-response property was demonstrated.

    更新日期:2020-01-26
  • Fast Isolation of Flavonoids from the Endemic Species Nolana ramosissima I.M. Johnst and its Endothelium-Independent Relaxation Effect in Rat Aorta
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Fredi Cifuentes; Javier Palacios; Jorge Bórquez; Adrián Paredes; Claudio Parra; Alejandra Bravo; Mario J. Simirgiotis

    The infusion of the desertic plant Nolana ramosissima I.M. Johnst showed vascular smooth muscle relaxation in rat aorta and the presence of several phenolic compounds, which were detected by high resolution UHPLC-Orbitrap-HESI-MS. In addition, five flavonoids were rapidly isolated from a methanolic extract using high-performance counter-current chromatography (HPCCC). The N. ramosissima extract showed endothelium-independent relaxation effect in rat aorta. Sixty-one compounds were detected in the infusion, mainly glycosylated flavonoids, flavanones and several oxylipins, suggesting that a synergistic effect between the compounds in the extracts could be responsible for the relaxation activity. Vascular activity experiments were done in isolated organ bath. In rat aorta, a nitric oxide inhibitor did not prevent the relaxation effects of the extract; however, a selective guanylyl cyclase inhibitor partially blunted this effect. The compound 5,3′-dihydroxy-4′7-dimethoxyflavone presented higher relaxation effect than 100 μg/mL of N. ramosissima extract. The extract and the isolated metabolites from N. ramosissima can show relaxation effects on rat aorta by a mechanism that is independent of the endothelium.

    更新日期:2020-01-24
  • Exopolyhedral Ligand Orientation Controls Diastereoisomer in Mixed-Metal Bis(carboranes)
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Antony P. Y. Chan; Georgina M. Rosair; Alan J. Welch

    Heterobimetallic derivatives of a bis(carborane), [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-(p-cymene)-closo-2,1,8-RuC2B9H10] (1) and [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-Cp-closo-2,1,8-CoC2B9H10] (2) have been synthesised and characterised, including crystallographic studies. A minor co-product during the synthesis of compound 2 is the new species [8-{8′-2′-H-2′,2′-(PPh3)2-closo-2′,1′,8′-RhC2B9H10}-2-Cp-closo-2,1,8-CoC2B9H10] (3), isolated as a mixture of diastereoisomers. Although, in principle, compounds 1 and 2 could also exist as two diastereoisomers, only one (the same in both cases) is formed. It is suggested that the preferred exopolyhedral ligand orientation in the rhodacarboranes in the non-observed diastereoisomers would lead to unacceptable steric crowding between the PPh3 ligand and either the p-cymene (compound 1) or Cp (compound 2) ligand of the ruthenacarborane or cobaltacarborane, respectively.

    更新日期:2020-01-24
  • The Effect of Polyphenols on Pomegranate Fruit Susceptibility to Pilidiella granati Provides Insights into Disease Tolerance Mechanisms
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Annamaria Mincuzzi; Antonio Ippolito; Virginia Brighenti; Lucia Marchetti; Stefania Benvenuti; Angela Ligorio; Federica Pellati; Simona Marianna Sanzani

    Pilidiella granati, also known as Coniella granati, is the etiological agent of pomegranate fruit dry rot. This fungal pathogen is also well-known as responsible for both plant collar rot and leaf spot. Because of its aggressiveness and the worldwide diffusion of pomegranate crops, the selection of cultivars less susceptible to this pathogen might represent an interesting preventive control measure. In the present investigation, the role of polyphenols in the susceptibility to P. granati of the two royalties-free pomegranate cultivars Wonderful and Mollar de Elche was compared. Pomegranate fruit were artificially inoculated and lesion diameters were monitored. Furthermore, pathogen DNA was quantified at 12–72 h post-inoculation within fruit rind by a real time PCR assay setup herein, and host total RNA was used in expression assays of genes involved in host-pathogen interaction. Similarly, protein extracts were employed to assess the specific activity of enzymes implicated in defense mechanisms. Pomegranate phenolic compounds were evaluated by HPLC-ESI-MS and MS2. All these data highlighted ‘Wonderful’ as less susceptible to P. granati than ‘Mollar de Elche’. In the first cultivar, the fungal growth seemed controlled by the activation of the phenylpropanoid pathway, the production of ROS, and the alteration of fungal cell wall. Furthermore, antifungal compounds seemed to accumulate in ‘Wonderful’ fruit following inoculation. These data suggest that pomegranate polyphenols have a protective effect against P. granati infection and their content might represent a relevant parameter in the selection of the most suitable cultivars to reduce the economic losses caused by this pathogen.

    更新日期:2020-01-24
  • Development and Validation of Methods for the Determination of Anthocyanins in Physiological Fluids via UHPLC-MSn
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Michael Kaiser; Lisa Müller-Ehl; Maike Passon; Andreas Schieber

    Recent in vitro and in vivo studies on anthocyanins confirmed numerous health-promoting effects in humans. Daily anthocyanin intake can be estimated via food databases, but the amount absorbed by the organism still remains uncertain because anthocyanin bioavailability is yet to be elucidated in its entirety. For this purpose, suitable and validated methods of sample preparation and analysis are required. Therefore, a sample preparation method for anthocyanin metabolite analysis in plasma was successfully established and validated. The validation yielded acceptable results for the anthocyanins in terms of recovery (54–108%) and precision (coefficient of variation (CV) < 15%). The UHPLC-MS method used in the consecutive reaction monitoring (CRM) mode was sufficiently sensitive, resulting in limits of detection <2.3 ng/mL and limits of quantification < 8.1 ng/mL with associated repeatability of the MS system with CVs of <5.1%. In addition, a method for the sum parameter determination of anthocyanidins in urine comprising solely the evaporation of acidified samples was developed, validated, and successfully applied to real samples. The results showed that this method is applicable for the methylated anthocyanidins, but not for the hydroxylated anthocyanidins, due to the chosen CRM modes required for optimum selectivity.

    更新日期:2020-01-24
  • Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Jingou Liang; Xinyu Peng; Xuedong Zhou; Jing Zou; Lei Cheng

    The oral cavity is a unique complex ecosystem colonized with huge numbers of microorganism species. Oral cavities are closely associated with oral health and sequentially with systemic health. Many factors might cause the shift of composition of oral microbiota, thus leading to the dysbiosis of oral micro-environment and oral infectious diseases. Local therapies and dental hygiene procedures are the main kinds of treatment. Currently, oral drug delivery systems (DDS) have drawn great attention, and are considered as important adjuvant therapy for oral infectious diseases. DDS are devices that could transport and release the therapeutic drugs or bioactive agents to a certain site and a certain rate in vivo. They could significantly increase the therapeutic effect and reduce the side effect compared with traditional medicine. In the review, emerging recent applications of DDS in the treatment for oral infectious diseases have been summarized, including dental caries, periodontitis, peri-implantitis and oral candidiasis. Furthermore, oral stimuli-responsive DDS, also known as “smart” DDS, have been reported recently, which could react to oral environment and provide more accurate drug delivery or release. In this article, oral smart DDS have also been reviewed. The limits have been discussed, and the research potential demonstrates good prospects.

    更新日期:2020-01-24
  • Bioassay-Guided Different Extraction Techniques of Carica papaya (Linn.) Leaves on In Vitro Wound-Healing Activities
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Husnul Hanani Soib; Hassan Fahmi Ismail; Fitrien Husin; Mohamad Hafizi Abu Bakar; Harisun Yaakob; Mohamad Roji Sarmidi

    Herbal plants are traditionally utilized to treat various illnesses. They contain phytochemicals that can be extracted using conventional methods such as maceration, soxhlet, and boiling, as well as non-conventional methods including ultrasonic, microwave, and others. Carica papaya leaves have been used for the treatment of dengue, fungal, and bacterial infections as well as an ingredient in anti-aging products. Phytochemicals analysis detected the presence of kaempferol, myricetin, carpaine, pseudocarpaine, dehydrocarpaine I and II, ferulic acid, caffeic acid, chlorogenic acid, β-carotene, lycopene, and anthraquinones glycoside. Conventional preparation by boiling and simple maceration is practical, simple, and safe; however, only polar phytochemicals are extracted. The present study aims to investigate the effects of three different non-conventional extraction techniques (ultrasonic-assisted extraction, reflux, and agitation) on C. papaya phytochemical constituents, the antioxidant capacity, and wound-healing activities. Among the three techniques, the reflux technique produced the highest extraction yield (17.86%) with the presence of saponins, flavonoids, coumarins, alkaloids, and phenolic metabolites. The reflux technique also produced the highest 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging with an IC50 value of 0.236 mg/mL followed by ultrasonic-assisted extraction (UAE) (IC50: 0.377 mg/mL) and agitation (IC50: 0.404 mg/mL). At tested concentrations (3.125 µg/mL to 500 µg/mL), all extracts do not exhibit a cytotoxicity effect on the human skin fibroblast, HSF1184. Interestingly, reflux and UAE were active fibroblast proliferators that support 85% (12.5 µg/mL) and 41% (6.25 µg/mL) better cell growth, respectively. Additionally, during the early 24 h of the scratch assay, the migration rate at 12.5 µg/mL was faster for all extracts with 51.8% (reflux), 49.3% (agitation), and 42.5% (UAE) as compared to control (21.87%). At 48 h, proliferated cells covered 78.7% of the scratch area for reflux extract, 63.1% for UAE, 61% for agitation, and 42.6% for control. Additionally, the collagen synthesis was enhanced for 31.6% and 65% after 24 and 48 h of treatment for reflux. An HPLC-MS/MS-QTOF (quadruple time-of-flight) analysis of reflux identified nine phytochemicals, including carpaine, kaempferol 3-(2G-glucosylrutinoside), kaempferol 3-(2''-rhamnosylgalactoside), 7-rhamnoside, kaempferol 3-rhamnosyl-(1->2)-galactoside-7-rhamnoside, luteolin 7-galactosyl-(1->6)-galactoside, orientin 7-O-rhamnoside, 11-hydroperoxy-12,13-epoxy-9-octadecenoic acid, palmitic amide, and 2-hexaprenyl-6-methoxyphenol. The results suggested that reflux was the best technique as compared to ultrasonic and agitation.

    更新日期:2020-01-24
  • Novel Approaches Utilizing Metal-Organic Framework Composites for the Extraction of Organic Compounds and Metal Traces from Fish and Seafood
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Sofia C. Vardali; Natalia Manousi; Mariusz Barczak; Dimitrios A. Giannakoudakis

    The determination of organic and inorganic pollutants in fish samples is a complex and demanding process, due to their high protein and fat content. Various novel sorbents including graphene, graphene oxide, molecular imprinted polymers, carbon nanotubes and metal-organic frameworks (MOFs) have been reported for the extraction and preconcentration of a wide range of contaminants from fish tissue. MOFs are crystalline porous materials that are composed of metal ions or clusters coordinated with organic linkers. Those materials exhibit extraordinary properties including high surface area, tunable pore size as well as good thermal and chemical stability. Therefore, metal-organic frameworks have been recently used in many fields of analytical chemistry including sample pretreatment, fabrication of stationary phases and chiral separations. Various MOFs, and especially their composites or hybrids, have been successfully utilized for the sample preparation of fish samples for the determination of organic (i.e., antibiotics, antimicrobial compounds, polycyclic aromatic hydrocarbons, etc.) and inorganic pollutants (i.e., mercury, palladium, cadmium, lead, etc.) as such or after functionalization with organic compounds.

    更新日期:2020-01-24
  • Understanding the Solution Behavior of Epinephrine in the Presence of Toxic Cations: A Thermodynamic Investigation in Different Experimental Conditions
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Francesco Crea; Concetta De Stefano; Anna Irto; Gabriele Lando; Stefano Materazzi; Demetrio Milea; Alberto Pettignano; Silvio Sammartano

    The interactions of epinephrine ((R)-(−)-3,4-dihydroxy-α-(methylaminomethyl)benzyl alcohol; Eph-) with different toxic cations (methylmercury(II): CH3Hg+; dimethyltin(IV): (CH3)2Sn2+; dioxouranium(VI): UO22+) were studied in NaClaq at different ionic strengths and at T = 298.15 K (T = 310.15 K for (CH3)2Sn2+). The enthalpy changes for the protonation of epinephrine and its complex formation with UO22+ were also determined using isoperibolic titration calorimetry: HHL = -39 ± 1 kJ mol-1, HH2L = -67 ± 1 kJ mol-1 (overall reaction), HML = -26 ± 4 kJ mol-1, and HM2L2(OH)2 = 39 ± 2 kJ mol-1. The results were that UO22+ complexation by Eph- was an entropy-driven process. The dependence on the ionic strength of protonation and the complex formation constants was modeled using the extended Debye–Hückel, specific ion interaction theory (SIT), and Pitzer approaches. The sequestering ability of adrenaline toward the investigated cations was evaluated using the calculation of pL0.5 parameters. The sequestering ability trend resulted in the following: UO22+ >> (CH3)2Sn2+ > CH3Hg+. For example, at I = 0.15 mol dm-3 and pH = 7.4 (pH = 9.5 for CH3Hg+), pL0.5 = 7.68, 5.64, and 2.40 for UO22+, (CH3)2Sn2+, and CH3Hg+, respectively. Here, the pH is with respect to ionic strength in terms of sequestration.

    更新日期:2020-01-24
  • Binaphthyl-Based Macrocycles as Optical Sensors for Aromatic Diphenols
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Stefano Piacentini; Marco Caricato; Aurora Pacini; Andrea Nitti; Dario Pasini

    The synthesis of several rigid, homochiral organic macrocycles possessing, respectively, average molecular D2 and D3 symmetries, is described. They have been obtained from aromatic dicarboxylic acids, in combination with an axially-chiral, suitable dibenzylic alcohol, derived from 1,1′-binaphthyl-2,2′-diol (BINOL) using one-pot esterification reactions in good isolated yields. NMR and circular dichroism (CD) spectroscopies detect the structural and shape variability in the scaffolds, reflected both in terms of the changes in chemical shifts and the shape of selected proton resonances, and in terms of the variation of the CD signature related to the dihedral angle defined by the binaphthyl units embedded in the rigid cyclic skeleton. The D2 cyclic adducts are able to form stable complexes with aromatic diphenols, with binding strengths that are dependent on small variations in the spacing units, and therefore on the shapes of the internal cavities of the cyclic structures.

    更新日期:2020-01-24
  • A Non-Targeted Capillary Electrophoresis-Mass Spectrometry Strategy to Study Metabolic Differences in an In vitro Model of High-Glucose Induced Changes in Human Proximal Tubular HK-2 Cells
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Samuel Bernardo-Bermejo; Elena Sánchez-López; María Castro-Puyana; Selma Benito-Martínez; Francisco Javier Lucio-Cazaña; María Luisa Marina

    Diabetic nephropathy is characterized by the chronic loss of kidney function due to high glucose renal levels. HK-2 proximal tubular cells are good candidates to study this disease. The aim of this work was to study an in vitro model of high glucose-induced metabolic alterations in HK-2 cells to contribute to the pathogenesis of this diabetic complication. An untargeted metabolomics strategy based on CE-MS was developed to find metabolites affected under high glucose conditions. Intracellular and extracellular fluids from HK-2 cells treated with 25 mM glucose (high glucose group), with 5.5 mM glucose (normal glucose group), and with 5.5 mM glucose and 19.5 mM mannitol (osmotic control group) were analyzed. The main changes induced by high glucose were found in the extracellular medium where increased levels of four amino acids were detected. Three of them (alanine, proline, and glutamic acid) were exported from HK-2 cells to the extracellular medium. Other affected metabolites include Amadori products and cysteine, which are more likely cause and consequence, respectively, of the oxidative stress induced by high glucose in HK-2 cells. The developed CE-MS platform provides valuable insight into high glucose-induced metabolic alterations in proximal tubular cells and allows identifying discriminative molecules of diabetic nephropathy.

    更新日期:2020-01-24
  • Bioactives From Agri-Food Wastes: Present Insights and Future Challenges
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Sana Ben-Othman; Ivi Jõudu; Rajeev Bhat

    Sustainable utilization of agri-food wastes and by-products for producing value-added products (for cosmetic, pharmaceutical or food industrial applications) provides an opportunity for earning additional income for the dependent industrial sector. Besides, effective valorisation of wastes/by-products can efficiently help in reducing environmental stress by decreasing unwarranted pollution. The major focus of this review is to provide comprehensive information on valorisation of agri-food wastes and by-products with focus laid on bioactive compounds and bioactivity. The review covers the bioactives identified from wastes and by-products of plants (fruits, exotic fruits, vegetables and seeds), animals (dairy and meat) and marine (fish, shellfish seaweeds) resources. Further, insights on the present status and future challenges of sustainably utilizing agri-food wastes/by-products for value addition will be highlighted.

    更新日期:2020-01-24
  • Production of Prenylated Stilbenoids in Hairy Root Cultures of Peanut (Arachis hypogaea) and its Wild Relatives A. ipaensis and A. duranensis via an Optimized Elicitation Procedure
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Lingling Fang; Tianhong Yang; Fabricio Medina-Bolivar

    Prenylated stilbenoids are phenolic compounds produced in a small number of plants such as peanut (Arachis hypogaea) to counteract biotic and abiotic stresses. In addition to their role in plant defense, they exhibit biological activities with potential application in human health. Whereas non-prenylated stilbenoids such as resveratrol are commercially available, the availability of prenylated stilbenoids is limited. To this end, hairy root cultures of peanut were developed as an elicitor-controlled bioproduction platform for prenylated stilbenoids. An orthogonal array design approach led to the elucidation of an optimized elicitation procedure consisting of co-treatment of the hairy root cultures with 18 g/L methyl-β-cyclodextrin, 125 µM methyl jasmonate, 3 mM hydrogen peroxide (H2O2) and medium supplementation with additional 1 mM magnesium chloride. After 168-h of elicitor treatment, the combined yield of the prenylated stilbenoids arachidin-1, arachidin-2, arachidin-3 and arachidin-5 reached approximately 750 mg/L (equivalent to 107 mg/g DW). Moreover, hairy root cultures from the wild Arachis species A. duranensis and A. ipaensis were developed and shown to produce prenylated stilbenoids upon elicitor treatment. These wild Arachis hairy root lines may provide a platform to elucidate the biosynthetic origin of prenylated stilbenoids in peanut.

    更新日期:2020-01-24
  • Visible-light Promoted Atom Transfer Radical Addition−Elimination (ATRE) Reaction for the Synthesis of Fluoroalkylated Alkenes Using DMA as Electron-Donor
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Wen-Wen Xu; Le Wang; Ting Mao; Jiwei Gu; Xiao-Fei Li; Chun-Yang He

    Here, we describe a mild, catalyst-free and operationally-simple strategy for the direct fluoroalkylation of olefins driven by the photochemical activity of an electron donor−acceptor (EDA) complex between DMA and fluoroalkyl iodides. The significant advantages of this photochemical transformation are high efficiency, excellent functional group tolerance, and synthetic simplicity, thus providing a facile route for further application in pharmaceuticals and life sciences.

    更新日期:2020-01-24
  • From Dermal Patch to Implants—Applications of Biocomposites in Living Tissues
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Karolina Papera Valente; Alexandre Brolo; Afzal Suleman

    Composites are composed of two or more materials, displaying enhanced performance and superior mechanical properties when compared to their individual components. The use of biocompatible materials has created a new category of biocomposites. Biocomposites can be applied to living tissues due to low toxicity, biodegradability and high biocompatibility. This review summarizes recent applications of biocomposite materials in the field of biomedical engineering, focusing on four areas—bone regeneration, orthopedic/dental implants, wound healing and tissue engineering.

    更新日期:2020-01-24
  • Synthesis of Biologically Active Molecules through Multicomponent Reactions
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Daniel Insuasty; Juan Castillo; Diana Becerra; Hugo Rojas; Rodrigo Abonia

    Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.

    更新日期:2020-01-24
  • Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses
    Molecules (IF 3.060) Pub Date : 2020-01-24
    Lamyae El Khalki; Virginie Maire; Thierry Dubois; Abdelmajid Zyad

    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC50 = 0.19 µM), BT-20 (IC50 = 0.23 µM) and MDA-MB-468 (IC50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

    更新日期:2020-01-24
  • Effectiveness of Different Analytical Methods for the Characterization of Propolis: A Case of Study in Northern Italy
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Radmila Pavlovic; Gigliola Borgonovo; Valeria Leoni; Luca Giupponi; Giulia Ceciliani; Stefano Sala; Angela Bassoli; Annamaria Giorgi

    : Propolis is used as folk medicine due to its spectrum of alleged biological and pharmaceutical properties and it is a complex matrix not still totally characterized. Two batches of propolis coming from two different environments (plains of Po Valley and the hilly Ligurian–Piedmont Apennines) of Northern Italy were characterized using different analytical methods: Spectrophotometric analysis of phenols, flavones and flavonols, and DPPH radical scavenging activity, HPLC, NMR, HSPME and GC–MS and HPLC–MS Orbitrap. Balsam and moisture content were also considered. No statistical differences were found at the spectrophotometric analysis; balsam content did not vary significantly. The most interesting findings were in the VOCs composition, with the Po Valley samples containing compounds of the resins from leaf buds of Populus nigra L. The hills (Appennines) samples were indeed characterize by the presence of phenolic glycerides already found in mountain environments. HPLC–Q-Exactive-Orbitrap®–MS analysis is crucial in appropriate recognition of evaluate number of metabolites, but also NMR itself could give more detailed information especially when isomeric compounds should be identified. It is necessary a standardized evaluation to protect and valorize this production and more research on propolis characterization using different analytical techniques.

    更新日期:2020-01-23
  • White Matter and Neuroprotection in Alzheimer’s Dementia
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Luca Lorenzini; Mercedes Fernandez; Vito Antonio Baldassarro; Andrea Bighinati; Alessandro Giuliani; Laura Calzà; Luciana Giardino

    Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in Alzheimer’s dementia (AD) and other neurodegenerative diseases, alterations which are early, extended, and regionally selective. Given that the white matter turnover is considerable in the adulthood, and that myelin repair is currently recognized as being the only true reparative capability of the mature CNS, oligodendrocyte precursor cells (OPCs), the cells that differentiate in oligodendrocyte, responsible for myelin formation and repair, are regarded as a potential target for neuroprotection. In this review, several aspects of the OPC biology are reviewed. The histology and functional role of OPCs in the neurovascular-neuroglial unit as described in preclinical and clinical studies on AD is discussed, such as the OPC vulnerability to hypoxia-ischemia, neuroinflammation, and amyloid deposition. Finally, the position of OPCs in drug discovery strategies for dementia is discussed.

    更新日期:2020-01-23
  • A New Method for Determination of Thymol and Carvacrol in Thymi herba by Ultraperformance Convergence Chromatography (UPC2)
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Xiaoqiang Chang; Peng Sun; Yue Ma; Dongchen Han; Yifan Zhao; Yue Bai; Dong Zhang; Lan Yang

    Ultraperformance convergence chromatography is an environmentally friendly analytical technique for dramatically reducing the use of organic solvents compared to conventional chromatographic methods. In this study, a rapid and sensitive ultraperformance convergence chromatography method was firstly established for quantification of thymol and carvacrol, two positional isomers of a major bioactive in the volatile oil of Thymi herba, the dried leaves and flowers of Thymus mongolicus or Thymus przewalskii, known in China as “Dijiao.” Using a TrefoilTM CEL1 column, thymol and carvacrol were separated in less than 2.5 min and resolution was enhanced. The method was validated with respect to precision, accuracy, and linearity according to the National Medical Products Administration guidelines. The optimized method exhibited good linear correlation (r = 0.9998−0.9999), excellent precision (relative standard deviations (RSDs) < 1.50%), and acceptable recoveries (87.29–102.89%). The limits of detection for thymol and carvacrol were 1.31 and 1.57 ng/L, respectively, while their corresponding limits of quantification were 2.63 and 3.14 ng/L. Finally, the quantities of the two compounds present in 16 T. mongolicus and four T. przewalskii samples were successfully evaluated by employing the developed method. It is hoped that the results of this study will serve as a guideline for the quality control of Thymi herba.

    更新日期:2020-01-23
  • Impacts of Chemical-Assisted Thermal Pretreatments on Methane Production from Fruit and Vegetable Harvesting Wastes: Process Optimization
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Ümmihan Günerhan; Ender Us; Lütfiye Dumlu; Vedat Yılmaz; Hélène Carrère; Altınay.N. Perendeci

    The increasing population creates excess pressure on the plantation and production of fruits and vegetables across the world. Consumption demand during the whole year has made production compulsory in the covered production system (greenhouse). Production, harvesting, processing, transporting, and distribution chains of fruit and vegetables have resulted in a huge amount of wastes as an alternative source to produce biofuels. In this study, optimization of two pretreatment processes (NaOH and HCl assisted thermal) was investigated to enhance methane production from fruit and vegetable harvesting wastes (FVHW) that originate from greenhouses. NaOH concentration (0–6.5%), HCl concentration (0–5%), reaction temperature (60–100 °C), solid content (1–5%), time of reaction (1–5 h), and mixing speed (0–500 rpm) were chosen in a wide range of levels to optimize the process in a broad design boundary and to evaluate the positive and negative impacts of independent variables along with their ranges. Increasing NaOH and HCl concentrations resulted in higher COD solubilization but decreased the concentration of soluble sugars that can be converted directly into methane. Thus, the increasing concentrations of NaOH and HCl in the pretreatments have resulted in low methane production. The most important independent variables impacting COD and sugar solubilization were found to be chemical concentration (as NaOH and HCl), solid content and reaction temperature for the optimization of pretreatment processes. The high amount of methane productions in the range of 222–365 mL CH4 gVS−1 was obtained by the simple thermal application without using chemical agents as NaOH or HCl. Maximum enhancement of methane production was 47–68% compared to raw FVHW when 5% solid content, 1-hour reaction time and 60–100 °C reaction temperature were applied in pretreatments.

    更新日期:2020-01-23
  • The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
    Molecules (IF 3.060) Pub Date : 2020-01-23
    So Hyun Park; Ji-Young Hong; Hyen Joo Park; Sang Kook Lee

    Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

    更新日期:2020-01-23
  • Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Junichi Okada; Eijiro Yamada; Tsugumichi Saito; Hideaki Yokoo; Aya Osaki; Yoko Shimoda; Atsushi Ozawa; Yasuyo Nakajima; Jeffrey E. Pessin; Shuichi Okada; Masanobu Yamada

    Dapagliflozin, empagliflozin, tofogliflozin, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2), is used clinically to reduce circulation glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose by the kidneys. Dapagliflozin is metabolized and inactivated by UGT1A9. Empagliflozin is metabolized and inactivated by UGT1A9 and by other related isoforms UGT2B7, UGT1A3, and UGT1A8. Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3. Dapagliflozin treatment of HCT116 cells, which express SGLT2 but not UGT1A9, results in the loss of cell adhesion, whereas HepG2 cells, which express both SGLT2 and UGT1A9, are resistant to the adhesion-related effects of dapagliflozin. PANC-1 and H1792 cells, which do not express either SGLT2 or UGT1A9, are also resistant to adhesion related effects of dapagliflozin. On the other hand, either empagliflozin or tofogliflozin treatment of HCT116, HepG2, PANC-1, and H1792 cells are resistant to the adhesion-related effects as observed in dapagliflozin treated HCT116 cells. Knockdown of UGT1A9 by shRNA in HepG2 cells increased dapagliflozin sensitivity, whereas the overexpression of UGT1A9 in HCT116 cells protected against dapagliflozin-dependent loos of cell adhesion. Dapagliflozin treatment had no effect on cellular interactions with fibronectin, vitronectin, or laminin, but it induced a loss of interaction with collagen I and IV. In parallel, dapagliflozin treatment reduced protein levels of the full-length discoidin domain receptor I (DDR1), concomitant with appearance of DDR1 cleavage products and ectodomain shedding of DDR1. In line with these observations, unmetabolized dapagliflozin increased ADAM10 activity. Dapagliflozin treatment also significantly reduced Y792 tyrosine phosphorylation of DDR1 leading to decrement of DDR1 function and detachment of cancer cells. Concomitant with these lines of results, we experienced that CEA in patients with colon cancer, which express SGLT2 but not UGT1A9, and type 2 diabetes mellitus treated by dapagliflozin in addition to chemotherapy was decreased (case 1). CEA in patients with colon cancer, which express SGLT2 but not UGT1A9, and type 2 diabetes mellitus was treated by dapagliflozin alone after radiation therapy was decreased but started to rise after cessation of dapagliflozin (case 2). CA19-9 in two of patients with pancreatic cancer and type 2 diabetes mellitus was resistant to the combination therapy of dapagliflozin and chemotherapy (case 3 and 4 respectively). PIVKAII in patients with liver cancer and type 2 diabetes mellitus, and CYFRA in patients with squamous lung cancer and type 2 diabetes mellitus was also resistant the combination therapy of dapagliflozin and chemotherapy (case 5 and 6 respectively). Taken together, these data suggest a potential role for dapagliflozin anticancer therapy against colon cancer cells that express SGLT2, but not UGT1A9.

    更新日期:2020-01-23
  • Non-Volatile Transistor Memory with a Polypeptide Dielectric
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Lijuan Liang; Wenjuan He; Rong Cao; Xianfu Wei; Sei Uemura; Toshihide Kamata; Kazuki Nakamura; Changshuai Ding; Xuying Liu; Norihisa Kobayashi

    Organic nonvolatile transistor memory with synthetic polypeptide derivatives as dielectric was fabricated by a solution process. When only poly (γ-benzyl-l-glutamate) (PBLG) was used as dielectric, the device did not show obvious hysteresis in transfer curves. However, PBLG blended with PMMA led to a remarkable increase in memory window up to 20 V. The device performance was observed to remarkably depend on the blend ratio. This study suggests the crystal structure and the molecular alignment significantly affect the electrical performance in transistor-type memory devices, thereby provides an alternative to prepare nonvolatile memory with polymer dielectrics.

    更新日期:2020-01-23
  • Fragaria Genus: Chemical Composition and Biological Activities
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Radu Claudiu Fierascu; Georgeta Temocico; Irina Fierascu; Alina Ortan; Narcisa Elena Babeanu

    The strawberries represent in our days one of the main fresh fruits consumed globally, inevitably leading to large amounts of by-products and wastes. Usually appreciated because of their specific flavor, the strawberries also possess biological properties, including antioxidant, antimicrobial, or anti-inflammatory effects. In spite of the wide spread of the Fragaria genus, few species represent the subject of the last decade scientific research. The main components identified in the Fragaria species are presented, as well as several biological properties, as emerging from the scientific papers published in the last decade.

    更新日期:2020-01-23
  • Abnormal Cannabidiol Affects Production of Pro-Inflammatory Mediators and Astrocyte Wound Closure in Primary Astrocytic-Microglial Cocultures
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Julian Cardinal von Widdern; Tim Hohmann; Faramarz Dehghani

    Abnormal cannabidiol (abn-CBD) exerts neuroprotective effects in vivo and in vitro. In the present study, we investigated the impact of abn-CBD on the glial production of proinflammatory mediators and scar formation within in vitro models. Primary astrocytic-microglial cocultures and astrocytic cultures from neonatal C57BL/6 mice and CB2 receptor knockout mice were stimulated with lipopolysaccharide (LPS), and the concentrations of tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and nitrite were determined. Furthermore, we performed a live cell microscopy-based scratch-wound assay. After LPS stimulation, TNFα, IL-6 and nitrite production was more strongly increased in cocultures than in isolated astrocytes. Abn-CBD treatment attenuated the LPS-induced production of TNFα and nitrite in cocultures, while IL-6 production remained unaltered. In isolated astrocytes, only LPS-induced TNFα production was reduced by abn-CBD. Similar effects were observed after abn-CBD application in cocultures of CB2 knockout mice. Interestingly, LPS-induced TNFα and nitrite levels were far lower in CB2 knockout cultures compared to wildtypes, while IL-6 levels did not differ. In the scratch-wound assay, treatment with abn-CBD decelerated wound closure when microglial cells were present. Our data shows a differential role of abn-CBD for modulation of glial inflammation and astrocytic scar formation. These findings provide new explanations for mechanisms behind the neuroprotective potential of abn-CBD.

    更新日期:2020-01-23
  • Chicken Heads as a Promising By-Product for Preparation of Food Gelatins
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Robert Gál; Pavel Mokrejš; Petr Mrázek; Jana Pavlačková; Dagmar Janáčová; Jana Orsavová

    Every year, the poultry industry produces a large number of by-products such as chicken heads containing a considerable proportion of proteins, particularly collagen. To prepare gelatin is one of the possibilities to advantageously utilize these by-products as raw materials. The aim of the paper was to process chicken heads into gelatins. An innovative method for conditioning starting raw material was using the proteolytic enzyme. Three technological factors influencing the yield and properties of extracted gelatins were monitored including the amount of enzyme used in the conditioning of the raw material (0.4% and 1.6%), the time of the conditioning (18 and 48 h), and the first gelatin extraction time (1 and 4 h). The gelatin yield was between 20% and 36%. The gelatin gel strength ranged from 113 to 355 Bloom. The viscosity of the gelatin solution was determined between 1.4 and 9.5 mPa.s. The content of inorganic solids varied from 2.3% to 3.9% and the melting point of the gelatin gel was recorded between 34.5 and 42.2 °C. This study has shown that gelatin obtained from chicken heads has a promising potential with diverse possible applications in the food industry, pharmacy, and cosmetics.

    更新日期:2020-01-23
  • Simple Syntheses of New Pegylated Trehalose Derivatives as a Chemical Tool for Potential Evaluation of Cryoprotectant Effects on Cell Membrane
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Karel Pomeisl; Jan Richter; Martin Golan; Irena Kratochvílová

    In our work, we developed the synthesis of new polyfunctional pegylated trehalose derivatives and evaluated their cryoprotective effect using flow cytometry. We showed that new compounds (modified trehaloses) bound to appropriate extracellular polymeric cryoprotectants could be helpful as a chemical tool for the evaluation of their potential toxic cell membrane influences. Our aim was to form a chemical tool for the evaluation of cryoprotectant cell membrane influences, which are still not easily predicted during the freezing/thawing process. We combined two basic cryoprotectants: polyethyleneglycols (PEGs) and trehalose in the new chemical compounds—pegylated trehalose hybrids. If PEG and trehalose are chemically bound and trehalose is adsorbed on the cell surface PEGs molecules which are, due to the chemical bonding with trehalose, close to the cell surface, can remove the cell surface hydration layer which destabilizes the cell membrane. This was confirmed by the comparison of new material, PEG, trehalose, and their mixture cryoprotective capabilities.

    更新日期:2020-01-23
  • Redox-Modulations of Photophysical and Single-molecule Magnet Properties in Ytterbium Complexes Involving Extended-TTF Triads
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Bertrand Lefeuvre; Jessica Flores Gonzalez; Frédéric Gendron; Vincent Dorcet; François Riobé; Vladimir Cherkasov; Olivier Maury; Boris Le Guennic; Olivier Cador; Viacheslav Kuropatov; Fabrice Pointillart

    The reaction between the 2,2’-benzene-1,4-diylbis(6-hydroxy-4,7-di-tert-butyl-1,3-benzodithiol-2-ylium-5-olate triad (H2SQ) and the metallo-precursor [Yb(hfac)3]2H2O led to the formation of a dinuclear coordination complex of formula [Yb2(hfac)6(H2SQ)]0.5CH2Cl2 (H2SQ-Yb). After chemical oxidation of H2SQ in 2,2’-cyclohexa-2,5-diene-1,4-diylidenebis(4,7-di-tert-butyl-1,3-benzodithiole-5,6-dione (Q), the latter triad reacted with the [Yb(hfac)3]2H2O precursor to give the dinuclear complex of formula [Yb2(hfac)6(Q)] (Q-Yb). Both dinuclear compounds have been characterized by X-ray diffraction, DFT optimized structure and electronic absorption spectra. They behaved as field-induced Single-Molecule Magnets (SMMs) nevertheless the chemical oxidation of the semiquinone to quinone moieties accelerated by a factor of five the relaxation time of the magnetization of Q-Yb compared to the one for H2SQ-Yb. The H2SQ triad efficiently sensitized the YbIII luminescence while the chemical oxidation of H2SQ into Q induced strong modification of the absorption properties and thus a quenching of the YbIII luminescence for Q-Yb. In other words, both magnetic modulation and luminescence quenching are reached by the oxidation of the protonated semiquinone into quinone.

    更新日期:2020-01-23
  • Biological Activities of Gedunin—A Limonoid from the Meliaceae Family
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Teresa M. Braga; Lídia Rocha; Tsz Yan Chung; Rita F. Oliveira; Cláudia Pinho; Ana I. Oliveira; Joaquim Morgado; Agostinho Cruz

    Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.

    更新日期:2020-01-23
  • Towards the Properties of Different Biomass-Derived Proteins via Various Extraction Methods
    Molecules (IF 3.060) Pub Date : 2020-01-23
    Lin Du; Pablo J. Arauzo; Maria Fernanda Meza Zavala; Zebin Cao; Maciej Pawel Olszewski; Andrea Kruse

    This study selected three representative protein-rich biomass—brewer’s spent grain (BSG), pasture grass (PG), and cyanobacteria (Arthrospira platensis; AP) for protein extraction with different extraction methods (alkaline treatment, aqueous extraction, and subcritical water extraction). The yield, purity, molecular weight, oil–water interfacial tension, and thermal stability of the obtained proteins derived from different biomass and extraction methods were comprehensively characterized and compared. In the view of protein yield and purity, alkaline treatment was found optimal for BSG (21.4 and 60.2 wt.%, respectively) and AP (55.5 and 68.8 wt.%, respectively). With the decreased oil–water interfacial tension, the proteins from all biomass showed the potential to be emulsifier. BSG and AP protein obtained with chemical treatment presented excellent thermal stability. As a novel method, subcritical water extraction is promising in recovering protein from all three biomass with the comparable yield and purity as alkaline treatment. Furthermore, the hydrolyzed protein with lower molecular weight by subcritical water could promote its functions of foaming and emulsifying.

    更新日期:2020-01-23
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