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Molecules, Volume 23, Issue 6 (June 2018)

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Open AccessArticle Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety
Molecules 2018, 23(6), 1497; https://doi.org/10.3390/molecules23061497 (registering DOI)
Received: 2 June 2018 / Revised: 15 June 2018 / Accepted: 16 June 2018 / Published: 20 June 2018
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Abstract
A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in
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A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC50 values in the range of 1.23–7.39 µM. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N′-[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N′-[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC50 values, the compound 5e seems to be leading compound for further development as anticancer agent. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Constituents of Essential Oil and Lipid Fraction from the Aerial Part of Bupleurum scorzonerifolium Willd. (Apiaceae) from Different Habitats
Molecules 2018, 23(6), 1496; https://doi.org/10.3390/molecules23061496 (registering DOI)
Received: 9 May 2018 / Revised: 12 June 2018 / Accepted: 16 June 2018 / Published: 20 June 2018
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Abstract
The essential oils and lipid fraction extracted from the aerial parts of Bupleurum scorzonerifolium were determined by a GC-MS method. In total, up to 67 components were identified. cis-β-Ocimene, trans-β-ocimene, limonene, α-pinene, α-copaene, β-elemene,
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The essential oils and lipid fraction extracted from the aerial parts of Bupleurum scorzonerifolium were determined by a GC-MS method. In total, up to 67 components were identified. cis-β-Ocimene, trans-β-ocimene, limonene, α-pinene, α-copaene, β-elemene, and caryophyllene oxide were recognized as consistent components of the essential oil extracted from the aerial parts of B. scorzonerifolium, regardless of the habitat. The content of these components varied from traces to a significant amount. The volume of the lipid fraction varied from 2.73 to 9.38%. In total, 23 components were identified, including 20 fatty acids, two sterols, and one ketone. The major fatty acid components identified were 16:0, 18:2n9, and 18:1n9. The total content of these fatty acids reached up to 76.19%. The lipid fraction of the aerial parts of B. scorzonerifolium predominantly contained MUFA and PUFA, which confirmed the pharmacological value of the species. The main factors affecting the composition of essential oils and lipid fractions of B. scorzonerifolium are environmental ones that determine the moisture supply to the plants in semiarid and arid areas. Full article
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Open AccessArticle Evaluation of the Effects of Isolated Lignin on Cellulose Enzymatic Hydrolysis of Corn Stover Pretreatment by NaOH Combined with Ozone
Molecules 2018, 23(6), 1495; https://doi.org/10.3390/molecules23061495 (registering DOI)
Received: 3 May 2018 / Revised: 16 June 2018 / Accepted: 17 June 2018 / Published: 20 June 2018
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Abstract
In this experiment, corn stover was treated with optimal combined pretreatment conditions: 2% NaOH at 80 °C treated 2 h combined with initial pH 9 at the ozone concentration of 78 mg/mL treated 25 min. The effect of lignin removal rate on the
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In this experiment, corn stover was treated with optimal combined pretreatment conditions: 2% NaOH at 80 °C treated 2 h combined with initial pH 9 at the ozone concentration of 78 mg/mL treated 25 min. The effect of lignin removal rate on the enzymatic hydrolysis degree of cellulose during the treatment process was studied. At the same time, the lignin in the optimal pretreated corn stover was separated and extracted by enzymatic acidolysis, and its structure and connection were characterized. The results showed that the alkali combined with ozone pretreatment improved the enzymatic hydrolysis degree of the cellulose while exfoliating and degrading the macromolecular lignin into small molecules. The stable crosslink structure of the lignin-cellulose-hemicellulose was destroyed, and the lignocellulosic structure changed in favor of the enzymatic hydrolysis of the cellulose. Full article
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Open AccessFeature PaperArticle Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species
Molecules 2018, 23(6), 1494; https://doi.org/10.3390/molecules23061494 (registering DOI)
Received: 2 June 2018 / Revised: 15 June 2018 / Accepted: 18 June 2018 / Published: 20 June 2018
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Abstract
The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both
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The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI50 of 0.17 μM, while compound 1 had a mean GI50 of 8.7 μM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI50 of 0.3 μg·mL−1). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessFeature PaperReview Synthesis and Reactions of α-Hydroxyphosphonates
Molecules 2018, 23(6), 1493; https://doi.org/10.3390/molecules23061493 (registering DOI)
Received: 8 May 2018 / Revised: 11 June 2018 / Accepted: 16 June 2018 / Published: 20 June 2018
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Abstract
This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other
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This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other valuable derivatives. O-Alkylation and O-acylation are typical reactions to afford α-alkoxy-, or α-acyloxyphosphonates, respectively. The oxidation of hydroxyphosphonates leads to ketophosphonates. The hydroxy function at the α carbon atom of hydroxyphosphonates may be replaced by a halogen atom. α-Aminophosphonates formed in the nucleophilic substitution reaction of α-hydroxyphosphonates with primary or secondary amines are also potentially bioactive compounds. Another typical reaction is the base-catalyzed rearrangement of α-hydroxy-phosphonates to phosphates. Hydrolysis of the ester function of hydroxyphosphonates leads to the corresponding phosphonic acids. Full article
(This article belongs to the Special Issue Organophosphorus Chemistry 2018)
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Open AccessArticle Identification of 2′,4′-Dihydroxychalcone as an Antivirulence Agent Targeting HlyU, a Master Virulence Regulator in Vibrio vulnificus
Molecules 2018, 23(6), 1492; https://doi.org/10.3390/molecules23061492 (registering DOI)
Received: 9 May 2018 / Revised: 14 June 2018 / Accepted: 19 June 2018 / Published: 20 June 2018
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Abstract
The emergence of antimicrobial resistance and rapid acclimation allows Vibrio vulnificus to rapidly propagate in the host. This problematic pathological scenario can be circumvented by employing an antivirulence strategy, treating Vibrio infections without hindering the bacterial growth. We developed a genome-integrated orthogonal inhibitor
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The emergence of antimicrobial resistance and rapid acclimation allows Vibrio vulnificus to rapidly propagate in the host. This problematic pathological scenario can be circumvented by employing an antivirulence strategy, treating Vibrio infections without hindering the bacterial growth. We developed a genome-integrated orthogonal inhibitor screening platform in E. coli to identify antivirulence agents targeting a master virulence regulator of V. vulnificus. We identified 2′,4′-dihydroxychalcone (DHC) from the natural compound library and verified that it decreases the expression of the major toxin network which is equivalent to the ∆hlyU deletion mutant. 2′,4′-DHC also reduced the hemolytic activity of V. vulnificus which was tested as an example of virulence phenotype. The electrophoretic mobility shift assay confirmed that 2′,4′-DHC specifically targeted HlyU and inhibited its binding to PrtxA1 promoter. Under in vivo conditions, a single dose of 2′,4′-DHC protected ~50% wax-worm larvae from V. vulnificus infection at a non-toxic concentration to both V. vulnificus and wax-worm larvae. In the current study, we demonstrated that an orthogonal reporter system is suitable for the identification of antivirulence compounds with accuracy, and identified 2′,4′-DHC as a potent antivirulence agent that specifically targets the HlyU virulence transcriptional regulator and significantly reduces the virulence and infection potential of V. vulnificus. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Expression, Purification, and Characterization of a Novel Hybrid Peptide with Potent Antibacterial Activity
Molecules 2018, 23(6), 1491; https://doi.org/10.3390/molecules23061491 (registering DOI)
Received: 16 April 2018 / Revised: 28 May 2018 / Accepted: 30 May 2018 / Published: 20 June 2018
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Abstract
The hybrid peptide cecropin A (1–8)–LL37 (17–30) (C–L), derived from the sequence of cecropin A (C) and LL-37 (L), showed significantly increased antibacterial activity and minimized hemolytic activity than C and L alone. To obtain high-level production of C–L, the deoxyribonucleic acid sequence
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The hybrid peptide cecropin A (1–8)–LL37 (17–30) (C–L), derived from the sequence of cecropin A (C) and LL-37 (L), showed significantly increased antibacterial activity and minimized hemolytic activity than C and L alone. To obtain high-level production of C–L, the deoxyribonucleic acid sequence encoding C–L with preferred codons was cloned into pET-SUMO to construct a fusion expression vector, and overexpressed in Escherichia coli (E. coli) BL21 (DE3). The maximum fusion protein (92% purity) was obtained with the yield of 89.14 mg/L fermentation culture after purification with Ni-NTA Sepharose column. The hybrid C–L was cleaved from the fusion protein by SUMO-protease, and 17.54 mg/L pure active C–L was obtained. Furthermore, the purified C–L showed identical antibacterial and hemolytic activity to synthesized C–L. Stability analysis results exhibited that the activity of C–L changed little below 80 °C for 20 min, but when the temperature exceeded 80 °C, a significant decrease was observed. Varying the pH from 5.0 to 10.0 did not appear to influence the activity of C–L, however, pH below 4.0 decreased the antibacterial activity of C–L rapidly. Under the challenge of several proteases (pepsin, trypsin, and proteinase K), the functional activity of C–L was maintained over 50%. In summary, this study not only supplied an effective approach for high-level production of hybrid peptide C–L, but paved the way for its further exploration in controlling infectious diseases of farm animals or even humans. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
Molecules 2018, 23(6), 1490; https://doi.org/10.3390/molecules23061490 (registering DOI)
Received: 5 May 2018 / Revised: 6 June 2018 / Accepted: 15 June 2018 / Published: 20 June 2018
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Abstract
Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA)
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Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy. Full article
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Open AccessArticle Mouse β-Defensin 3, A Defensin Inhibitor of Both Its Endogenous and Exogenous Potassium Channels
Molecules 2018, 23(6), 1489; https://doi.org/10.3390/molecules23061489 (registering DOI)
Received: 6 May 2018 / Revised: 9 June 2018 / Accepted: 11 June 2018 / Published: 20 June 2018
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Abstract
The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse β-defensin 3 (mBD3) was a novel inhibitor
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The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse β-defensin 3 (mBD3) was a novel inhibitor of both endogenous and exogenous potassium channels. The structural analysis showed that mBD3 is the most identical to human Kv1.3 channel-sensitive human β-defensin 2 (hBD2). However, the pharmacological profiles indicated that the recombinant mBD3 (rmBD3) weakly inhibited the mouse and human Kv1.3 channels. Different from the pharmacological features of human β-defensins, mBD3 more selectively inhibited the mouse Kv1.6 and human KCNQ1/KCNE1 channels with IC50 values of 0.6 ± 0.4 μM and 1.2 ± 0.8 μM, respectively. The site directed mutagenesis experiments indicated that the extracellular pore region of mouse Kv1.6 channel was the interaction site of rmBD3. In addition, the minor effect on the channel conductance-voltage relationship curves implied that mBD3 might bind the extracellular transmembrane helices S1-S2 linker and/or S3-S4 linker of mouse Kv1.6 channel. Together, these findings not only revealed mBD3 as a novel inhibitor of both endogenous and exogenous potassium channels, but also provided a clue to investigate the role of mBD3-Kv1.6 channel interaction in the physiological and pathological field in the future. Full article
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Open AccessArticle Insights into Resistance Mechanisms of Inhibitors to Mps1 C604Y Mutation via a Comprehensive Molecular Modeling Study
Molecules 2018, 23(6), 1488; https://doi.org/10.3390/molecules23061488 (registering DOI)
Received: 8 May 2018 / Revised: 7 June 2018 / Accepted: 13 June 2018 / Published: 20 June 2018
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Abstract
Mono-polar spindle 1 (Mps1/TTK) represents a protein kinase reported to be vital for cell division processes and is generally regarded as an attractive target for the treatment of hepatocellular carcinoma, breast carcinoma, and colon cancer. However, the C604Y mutation has been linked to
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Mono-polar spindle 1 (Mps1/TTK) represents a protein kinase reported to be vital for cell division processes and is generally regarded as an attractive target for the treatment of hepatocellular carcinoma, breast carcinoma, and colon cancer. However, the C604Y mutation has been linked to acquired resistance. Recently, three potential small-molecule inhibitors of Mps1 (i.e., reversine, NMS-P715, and its derivative Cpd-5) were reported for the C604Y mutation that exhibit significant resistance to NMS-P715 and Cpd-5, but retain affinity for reversine. In this study, classical molecular dynamic (MD) simulations, accelerated MD (aMD) simulations, and umbrella sampling (US) simulations were performed to illustrate the resistance mechanisms of inhibitors to Mps1. The classical MD simulations combined with free energy calculations revealed that reversine features similar binding affinity characteristics to both Mps1WT and Mps1C604Y, but both NMS-P715 and Cpd-5 feature much higher binding affinities to Mps1WT than to Mps1C604Y. The major variations were shown to be controlled by electrostatic energy and the conformational change of A-loop-induced entropy increased. The large conformational changes of Mps1C604Y bound to NMS-P715 and Cpd-5 were also observed in aMD simulations. The US simulation results further suggest that reversine and Cpd-5 both exhibit similar dissociation processes from both Mps1WT and Mps1C604Y, but Cpd-5 and NMS-P715 were found to dissociate more easily from Mps1C604Y than from Mps1WT, thus a reduced residence time was responsible for the inhibitors resistance to the C604Y mutation. The physical principles provided by the present study may provide important clues for the discovery and rational design of novel inhibitors to combat the C604Y mutation of Mps1. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle Upregulation of UDP-Glucuronosyltransferases 1a1 and 1a7 Are Involved in Altered Puerarin Pharmacokinetics in Type II Diabetic Rats
Molecules 2018, 23(6), 1487; https://doi.org/10.3390/molecules23061487 (registering DOI)
Received: 1 June 2018 / Revised: 17 June 2018 / Accepted: 17 June 2018 / Published: 20 June 2018
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Abstract
Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of
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Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of puerarin in normal rats and rats with diabetes mellitus (DM), and the mechanism involved. DM was induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection. Plasma concentrations of puerarin in DM, HFD, and control rats were determined after intravenous (20 mg/kg) and oral administration (500 mg/kg) of puerarin, and pharmacokinetic parameters were estimated. The messenger RNA (mRNA) and protein expression levels of Ugt1a1 and Ugt1a7 in rat livers and intestines were measured using qRT-PCR and western blot, respectively. The area under the concentration–time curve and the clearance of puerarin in the DM rats statistically differed from those in the control rats (p <0.05) with both administration routes. The hepatic and intestinal gene and protein expressions of Ugt1a1 and Ugt1a7 were significantly increased in the DM rats (p <0.05). Therefore, the metabolic changes in diabetes could alter the pharmacokinetics of puerarin. This change could be caused by upregulated uridine diphosphate (UDP)-glucuronosyltransferase activity, which may enhance puerarin clearance, and alter its therapeutic effects. Full article
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Open AccessReview Mitochondria-Targeting Small Molecules Effectively Prevent Cardiotoxicity Induced by Doxorubicin
Molecules 2018, 23(6), 1486; https://doi.org/10.3390/molecules23061486
Received: 22 May 2018 / Revised: 13 June 2018 / Accepted: 13 June 2018 / Published: 19 June 2018
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Abstract
Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a
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Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a variety of small molecules that target mitochondria to modulate Dox-induced cardiotoxicity have appeared in recent years. Here, we review the related literatures and discuss the evidence showing that mitochondria-targeting small molecules are promising cardioprotective agents against Dox-induced cardiac events. Full article
(This article belongs to the Special Issue Recent Advances in Anticancer Drugs)
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Open AccessArticle A Novel Cyclodextrin-Functionalized Hybrid Silicon Wastewater Nano-Adsorbent Material and Its Adsorption Properties
Molecules 2018, 23(6), 1485; https://doi.org/10.3390/molecules23061485
Received: 20 May 2018 / Revised: 9 June 2018 / Accepted: 13 June 2018 / Published: 19 June 2018
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Abstract
A novel cyclodextrin-functionalized hybrid silicon nano-adsorbent material (6-EA-β-CD-Si) was synthesized via the nucleophilic substitution method. The structure was detected by Fourier transform infrared (FT-IR), X-ray, thermogravimetric analysis, and Brunauer-Emmett-Teller (BET) analysis. Results reveal that the BET surface area of 6-EA-β-CD-Si is 240 m
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A novel cyclodextrin-functionalized hybrid silicon nano-adsorbent material (6-EA-β-CD-Si) was synthesized via the nucleophilic substitution method. The structure was detected by Fourier transform infrared (FT-IR), X-ray, thermogravimetric analysis, and Brunauer-Emmett-Teller (BET) analysis. Results reveal that the BET surface area of 6-EA-β-CD-Si is 240 m2/g and the average pore size is 4.16 nm. The adsorption properties of 6-EA-β-CD-Si onto methylene blue (MB) were studied and fitted with adsorption kinetic models. Both the Freundlich adsorption isotherm model and pseudo-second-order model were fitted with well shows that the multi-layer adsorption with chemisorption and physisorption co-existing in the system. The maximum adsorption capacities are 39.37, 39.21, 36.90, and 36.36 mg/g at temperatures 303, 313, 323, and 333 K, respectively. The maximum removal rate of MB could reach 99.5%, indicating the potential application value of 6-EA-β-CD-Si in wastewater treatment. The adsorption mechanisms of 6-EA-β-CD-Si showed that the hydrophobic cave of β-CD plays an important role on the adsorption of MB. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry 2018)
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Open AccessReview A Review of the Extraction and Determination Methods of Thirteen Essential Vitamins to the Human Body: An Update from 2010
Molecules 2018, 23(6), 1484; https://doi.org/10.3390/molecules23061484
Received: 11 May 2018 / Revised: 12 June 2018 / Accepted: 17 June 2018 / Published: 19 June 2018
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Abstract
Vitamins are a class of essential nutrients in the body; thus, they play important roles in human health. The chemicals are involved in many physiological functions and both their lack and excess can put health at risk. Therefore, the establishment of methods for
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Vitamins are a class of essential nutrients in the body; thus, they play important roles in human health. The chemicals are involved in many physiological functions and both their lack and excess can put health at risk. Therefore, the establishment of methods for monitoring vitamin concentrations in different matrices is necessary. In this review, an updated overview of the main pretreatments and determination methods that have been used since 2010 is given. Ultrasonic assisted extraction, liquid–liquid extraction, solid phase extraction and dispersive liquid–liquid microextraction are the most common pretreatment methods, while the determination methods involve chromatography methods, electrophoretic methods, microbiological assays, immunoassays, biosensors and several other methods. Different pretreatments and determination methods are discussed. Full article
(This article belongs to the Special Issue Modern Sample Preparation Approaches for Separation Science)
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Open AccessReview Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity
Molecules 2018, 23(6), 1483; https://doi.org/10.3390/molecules23061483
Received: 14 May 2018 / Revised: 13 June 2018 / Accepted: 15 June 2018 / Published: 19 June 2018
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Abstract
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with
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Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells. Full article
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