bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Ultrasound-Assisted Extraction Condition for Phenolic Compounds, Antioxidant Activity, and Epigallocatechin Gallate in Lipid-Extracted Microalgae
Authors: Gam Da Hye , Kim Song Yi , Kim Jin Woo
Published: January 2020

Lipid-extracted microalgae (LEM, Tetraselmis KCTC 12236BP), a solid waste by-product obtained from algal biodiesel production, is typically considered a rich source of antioxidant compounds, including phenolic compounds. The purpose of this study was to apply a statistically-based methodology to enhance the extraction of total phenolic compounds (TPCs) and antioxidant activity (AA) from LEM and to verify the production of epigallocatechin gallate (EGCG), a bioactive material, under optimum conditions. The optimal extractions of TPC and AA were explored by varying the key variables, including the extraction temperature, ethanol concentration, extraction time, and ultrasonic power, through statistical optimization. The optimal extraction conditions were identified through 27 runs following the central composite design. The regression analyses of TPC and AA showed good fit of the experimental data to the second-order polynomial models, with coefficient of determination (R2) values of 0.8769 and 0.8432, respectively. In the variation experiment, the maximum TPC and AA values of 9.8 mg GAE/g and 91.8% were obtained respectively with an extraction temperature of 74.4 °C, ethanol concentration of 55.4%, extraction time of 59.6 min, and ultrasonic power of 700 W. HPLC coupled with diode array detection was used to identify and quantify the phenolic compounds in the extracts, and EGCG (0.12 mg/g DM) was identified as a major peak in the analysis, demonstrating that high value-added material with a bioactive property can be produced from LEM. The results indicated that statistical optimization is applicable for optimizing the extraction of TPC and AA from LEM and provided a scientific basis for applying ultrasound-assisted extraction on an industrial scale by optimizing the conditions. LEM has a high TPC value, particularly with regard to EGCG, and excellent AA, considering it is highly used as a functional material for food, cosmetics, and medicine.
Cinnamic Derivatives as Antitubercular Agents: Characterization by Quantitative Structure–Activity Relationship Studies
Authors: Teixeira Cátia , Ventura Cristina , Gomes José R. B. , Gomes Paula , Martins Filomena
Published: January 2020

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains one of the top ten causes of death worldwide and the main cause of mortality from a single infectious agent. The upsurge of multi- and extensively-drug resistant tuberculosis cases calls for an urgent need to develop new and more effective antitubercular drugs. As the cinnamoyl scaffold is a privileged and important pharmacophore in medicinal chemistry, some studies were conducted to find novel cinnamic acid derivatives (CAD) potentially active against tuberculosis. In this context, we have engaged in the setting up of a quantitative structure–activity relationships (QSAR) strategy to: (i) derive through multiple linear regression analysis a statistically significant model to describe the antitubercular activity of CAD towards wild-type Mtb; and (ii) identify the most relevant properties with an impact on the antitubercular behavior of those derivatives. The best-found model involved only geometrical and electronic CAD related properties and was successfully challenged through strict internal and external validation procedures. The physicochemical information encoded by the identified descriptors can be used to propose specific structural modifications to design better CAD antitubercular compounds.
Interaction and Kinetics Study of the Co-Gasification of High-solid Anaerobic Digestate and Lignite
Authors: Chang Shengqiang , Zhang Zhikai , Cao Lixia , Ma Liqiang , Wang Fang , Li Jihui , Li Wangliang
Published: January 2020

This study aims at investigating the interaction and kinetics behavior of the co-gasification of digestate and lignite. The co-pyrolysis performances of digestate and lignite blended by dry process were better than that blended by wet process, while the wet-blending process could improve the performance in co-gasification stage because of the larger pore diameter and pore volume. When anaerobic digestion (AD) time was 40 days, the synergistic interaction between digestate and lignite were the most remarkable based on the results of thermogravimetric analysis (TG) and the experiments in the lab-scale downdraft fixed bed gasifier. Kinetics study showed that the increase of AD time and the addition of digestate in lignite decreased the activation energy of the co-gasification reaction.
Signalling and Bioactive Metabolites from Streptomyces sp. RK44
Authors: Fang Qing , Maglangit Fleurdeliz , Wu Linrui , Ebel Rainer , Kyeremeh Kwaku , Andersen Jeanette H. , Annang Frederick , Pérez-Moreno Guiomar , Reyes Fernando , Deng Hai
Published: January 2020

Streptomyces remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of Streptomyces sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) 1 together with five known compounds, cyclo-(L-Pro-Gly) 2, cyclo-(L-Pro-L-Phe) 3, cyclo-(L-Pro-L-Val) 4, cyclo-(L-Leu-Hyp) 5, and deferoxamine E 6. AHFA 1, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC50 = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08 µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, 7–12 and six siderophores 13–18.
Process Development and Synthesis of Process-Related Impurities of an Efficient Scale-Up Preparation of 5,2′-Dibromo-2,4′,5′-Trihydroxy Diphenylmethanone as a New Acute Pyelonephritis Candidate Drug
Authors: Feng Xiu E , Cui Ke Meng , Li Qing Shan , Wu Zi Cheng , Lei Fei
Published: January 2020

Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone (LM49-API), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of LM49-API and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of LM49-API. Its finalized preparation process was further validated at 329–410 g scale-up production in 53.4–57.1% overall yield with 99.95–99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production. LM49-API-imC and LM49-API-imX were identified as the main single impurities in LM49-API, with the content controlled to be less than 0.03%.
Pestalotiones A–D: Four New Secondary Metabolites from the Plant Endophytic Fungus Pestalotiopsis Theae
Authors: Guo Longfang , Lin Jie , Niu Shubin , Liu Shuchun , Liu Ling
Published: January 2020

Two new xanthone derivatives, pestalotiones A (1) and B (2), one new diphenyl ketone riboside, pestalotione C (7), and one new diphenyl ether, pestalotione D (8), along with five known compounds isosulochrin dehydrate (3), 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), isosulochrin (5), chloroisosulochrin (6), and pestalotether D (9), were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). The structures of the new compounds were unambiguously deduced by HRESIMS and 1D/2D-NMR spectroscopic data. Compound 6 showed modest cytotoxicity against the HeLa cell line with an IC50 value of 35.2 μM. Compound 9 also showed cytotoxic to the HeLa and MCF-7 cell lines, with IC50 values of 60.8 and 22.6 μM, respectively. Additionally, compounds 1 and 2 exhibited antioxidant activity in scavenging DPPH radical with IC50 values of 54.2 and 59.2 μg/mL, respectively.
NMR Relaxation Measurements on Complex Samples Based on Real-Time Pure Shift Techniques
Authors: Lin Xiaoqing , Zhan Haolin , Li Hong , Huang Yuqing , Chen Zhong
Published: January 2020

Longitudinal spin-lattice relaxation (T1) and transverse spin-spin relaxation (T2) reveal valuable information for studying molecular dynamics in NMR applications. Accurate relaxation measurements from conventional 1D proton spectra are generally subject to challenges of spectral congestion caused by J coupling splittings and spectral line broadenings due to magnetic field inhomogeneity. Here, we present an NMR relaxation method based on real-time pure shift techniques to overcome these two challenges and achieve accurate measurements of T1 and T2 relaxation times from complex samples that contain crowded NMR resonances even under inhomogeneous magnetic fields. Both theoretical analyses and detailed experiments are performed to demonstrate the effectiveness and ability of the proposed method for accurate relaxation measurements on complex samples and its practicability to non-ideal magnetic field conditions.
In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell
Authors: Al-Rikabi Rasha , Al-Shmgani Hanady , Dewir Yaser Hassan , El-Hendawy Salah
Published: January 2020

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.
Synthesis, Anticancer Activity, and Preliminary Pharmacokinetic Evaluation of 4,4-Disubstituted Curcuminoid 2,2-bis(Hydroxymethyl)Propionate Derivatives
Authors: Lee Der-Yen , Hou Yu-Chi , Yang Jai-Sing , Lin Hui-Yi , Chang Tsu-Yuan , Lee Kuo-Hsiung , Kuo Sheng-Chu , Hsieh Min-Tsang
Published: January 2020

Compound 1 is a curcumin di-O-2,2-bis(hydroxymethyl)propionate that shows significant in vitro and in vivo inhibitory activity against MDA-MB-231 cells with eight to ten-fold higher potency than curcumin. Here, we modified the α-position (C-4 position) of the central 1,3-diketone moiety of 1 with polar or nonpolar functional groups to afford a series of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)propionate derivatives and evaluated their anticancer activities. A clear structure–activity relationship of compound 1 derivatives focusing on the functional groups at the C-4 position was established based on their anti-proliferative effects against the MDA-MB-231 and HCT-116 cell lines. Compounds 2–6 are 4,4-dimethylated, 4,4-diethylated, 4,4-dibenzylated, 4,4-dipropargylated and 4,4-diallylated compound 1, respectively. Compounds 2m–6m, the ester hydrolysis products of compounds 2–6, respectively, were synthesized and assessed for anticancer activity. Among all compound 1 derivatives, compound 2 emerged as a potential chemotherapeutic agent for colon cancer due to the promising in vivo anti-proliferative activities of 2 (IC50 = 3.10 ± 0.29 μM) and its ester hydrolysis product 2m (IC50 = 2.17 ± 0.16 μM) against HCT-116. The preliminary pharmacokinetic evaluation of 2 implied that 2 and 2m are main contributors to the in vivo efficacy. Compound 2 was further evaluated in an animal study using HCT-116 colon tumor xenograft bearing nude mice. The results revealed a dose-dependent efficacy that led to tumor volume reductions of 27%, 45%, and 60% at 50, 100, and 150 mg/kg doses, respectively. The established structure–activity relationship and pharmacokinetic outcomes of 2 is the guidance for future development of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)- propionate derivatives as anticancer drug candidates.
Synthesis and Spectral Study of a New Family of 2,5-Diaryltriazoles Having Restricted Rotation of the 5-Aryl Substituent
Authors: Tsyrenova Biligma , Nenajdenko Valentine
Published: January 2020

Efficient synthesis of 2,5-diaryl substituted 4-azido-1,2,3-triazoles by the reaction of sodium azide with dichlorosubstituted diazadienes was demonstrated. The optical properties of the prepared azidotriazoles were studied to reveal a luminescence maximum in the 360–420 nm region. To improve the luminescence quantum yields a family of 4-azido-1,2,3-triazoles bearing ortho-propargyloxy substituents in the 5 position was prepared. Subsequent intramolecular thermal cyclization permits to construct additional triazole fragment and obtain unique benzoxazocine derivatives condensed with two triazole rings. This new family of condensed heterocycles has a flattened heterocyclic system structure to provide more conjugation of the 5-aryl fragment with the triazole core. As a result, a new type of UV/“blue light-emitting” materials with better photophysical properties was obtained.
Huntington’s Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers
Authors: Cybulska Klaudia , Perk Lars , Booij Jan , Laverman Peter , Rijpkema Mark
Published: January 2020

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by a CAG expansion mutation in the huntingtin gene. As a result, intranuclear inclusions of mutant huntingtin protein are formed, which damage striatal medium spiny neurons (MSNs). A review of Positron Emission Tomography (PET) studies relating to HD was performed, including clinical and preclinical data. PET is a powerful tool for visualisation of the HD pathology by non-invasive imaging of specific radiopharmaceuticals, which provide a detailed molecular snapshot of complex mechanistic pathways within the brain. Nowadays, radiochemists are equipped with an impressive arsenal of radioligands to accurately recognise particular receptors of interest. These include key biomarkers of HD: adenosine, cannabinoid, dopaminergic and glutamateric receptors, microglial activation, phosphodiesterase 10 A and synaptic vesicle proteins. This review aims to provide a radiochemical picture of the recent developments in the field of HD PET, with significant attention devoted to radiosynthetic routes towards the tracers relevant to this disease.
Small Peptide-Doxorubicin Co-Assembly for Synergistic Cancer Therapy
Authors: Li Shuangfei , Chen Xianglan , Chen Huirong , Peng Jiaofeng , Yang Xuewei
Published: January 2020

Design of elaborated nanomaterials to improve the therapeutic efficacy and mitigate the side effects of chemotherapeutic anticancer drugs, such as Doxorubicin (Dox), is significant for cancer treatment. Here, we describe a co-assembled strategy, where amphiphile short peptides are co-assembled with Doxorubicin to form nanoscale particles for enhanced delivery of Dox. Two kinds of short peptides, Fmoc-FK (FK) and Fmoc-FKK (FKK), are synthesized. Through adjusting the component ratio of peptide and Dox, we obtain two kinds of co-assembled nanoparticles with homogeneous size distributions. These nanoparticles show several distinct characteristics. First, they are pH-responsive as they are stable in alkaline and neutral conditions, however, de-assembly at acidic pH enables selective Dox release in malignant cancer cells. Second, the nanoparticles show an average size of 50–100 nm with positive charges, making them effective for uptake by tumor cells. Moreover, the side effects of Dox on healthy cells are mitigated due to decreased exposure of free-Dox to normal cells. To conclude, the co-assembled peptide-Dox nanoparticles exhibit increased cellular uptake compared to free-Dox, therefore causing significant cancer cell death. Further apoptosis and cell cycle analysis indicates that there is a synergistic effect between the peptide and Doxorubicin.
Identification and Characterization of pantocin wh-1, a Novel Cyclic Polypeptide Produced by Pantoea dispersa W18
Authors: Teng Tieshan , Li Xianghui , Zhang Lei , Li Yanzhang
Published: January 2020

Pantoea dispersa W18, isolated from contaminated soil, was found to exert antimicrobial activity against Mycobacterium species, including Mycobacterium tuberculosis, an important human pathogen. Here, the anti-mycobacterial compound produced by Pantoea dispersa W18 was purified by a combination of hydrophobic interaction chromatography, cation exchange chromatography, and reverse phase HPLC. Active compounds from Pantoea dispersa W18 were identified as a natural peptide named pantocin wh-1 with a 1927 Da molecular weight. The primary structure of this compound was detected by N-terminal amino acid sequencing. The amino acid sequence of pantocin wh-1 consisted of 16 amino acid residues with a cyclic structure. The pantocin wh-1 could be inactivated by protease K, but was heat stable and unaffected by pH (2–12). However, the activity was not completely inactivated by trypsin and pepsin. This is the first report of a cyclic polypeptide purified from a strain of Pantoea dispersa.
Phase Transition of Ice at High Pressures and Low Temperatures
Authors: Xu Jinjin , Liu Jinfeng , Liu Jinyun , Hu Wenxin , He Xiao , Li Jinjin
Published: January 2020

The behavior of ice under extreme conditions undergoes the change of intermolecular binding patterns and leads to the structural phase transitions, which are needed for modeling the convection and internal structure of the giant planets and moons of the solar system as well as H2O-rich exoplanets. Such extreme conditions limit the structural explorations in laboratory but open a door for the theoretical study. The ice phases IX and XIII are located in the high pressure and low temperature region of the phase diagram. However, to the best of our knowledge, the phase transition boundary between these two phases is still not clear. In this work, based on the second-order Møller–Plesset perturbation (MP2) theory, we theoretically investigate the ice phases IX and XIII and predict their structures, vibrational spectra and Gibbs free energies at various extreme conditions, and for the first time confirm that the phase transition from ice IX to XIII can occur around 0.30 GPa and 154 K. The proposed work, taking into account the many-body electrostatic effect and the dispersion interactions from the first principles, opens up the possibility of completing the ice phase diagram and provides an efficient method to explore new phases of molecular crystals.
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases
Authors: Janicka Małgorzata , Sztanke Małgorzata , Sztanke Krzysztof
Published: January 2020

The permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was used to predict the penetration of the blood-brain barrier by 65 newly-synthesized drug-like compounds. The linear free energy relationships (LFERs) model (log BB = c + eE + sS + aA + bB + vV) was established for a training set of 23 congeneric biologically active azole compounds with known experimental log BB (BB = Cblood/Cbrain) values (R2 = 0.9039). The reliability and predictive potency of the model were confirmed by leave-one-out cross validation as well as leave-50%-out cross validation. Multiple linear regression (MLR) was used to develop the quantitative structure-activity relationships (QSARs) to predict the log BB values of compounds that were tested, taking into account the chromatographic lipophilicity (log kw), polarizability and topological polar surface area. The excellent statistics of the developed MLR equations (R2 > 0.8 for all columns) showed that it is possible to use the HPLC technique and retention data to produce reliable blood-brain barrier permeability models and to predict the log BB values of our pharmaceutically important molecules.
Towards the Properties of Different Biomass-Derived Proteins via Various Extraction Methods
Authors: Du Lin , Arauzo Pablo J. , Meza Zavala Maria Fernanda , Cao Zebin , Olszewski Maciej Pawel , Kruse Andrea
Published: January 2020

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.
Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer’s Diseases
Authors: Guo Yan , Yang Hongyu , Huang Zhongwei , Tian Sen , Li Qihang , Du Chenxi , Chen Tingkai , Liu Yang , Sun Haopeng , Liu Zongliang
Published: January 2020

A series of novel compounds 6a–h, 8i–1, 10s–v, and 16a–d were synthesized and evaluated, together with the known analogs 11a–f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 μM) and BChE (eqBChE IC50 = 0.28 μM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.
Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma
Authors: Šamec Neja , Zottel Alja , Videtič Paska Alja , Jovčevska Ivana
Published: January 2020

Owing to the advancement of technology combined with our deeper knowledge of human nature and diseases, we are able to move towards precision medicine, where patients are treated at the individual level in concordance with their genetic profiles. Lately, the integration of nanoparticles in biotechnology and their applications in medicine has allowed us to diagnose and treat disease better and more precisely. As a model disease, we used a grade IV malignant brain tumor (glioblastoma). Significant improvements in diagnosis were achieved with the application of fluorescent nanoparticles for intraoperative magnetic resonance imaging (MRI), allowing for improved tumor cell visibility and increasing the extent of the surgical resection, leading to better patient response. Fluorescent probes can be engineered to be activated through different molecular pathways, which will open the path to individualized glioblastoma diagnosis, monitoring, and treatment. Nanoparticles are also extensively studied as nanovehicles for targeted delivery and more controlled medication release, and some nanomedicines are already in early phases of clinical trials. Moreover, sampling biological fluids will give new insights into glioblastoma pathogenesis due to the presence of extracellular vesicles, circulating tumor cells, and circulating tumor DNA. As current glioblastoma therapy does not provide good quality of life for patients, other approaches such as immunotherapy are explored. To conclude, we reason that development of personalized therapies based on a patient’s genetic signature combined with pharmacogenomics and immunogenomic information will significantly change the outcome of glioblastoma patients.
Biological Activities of Gedunin—A Limonoid from the Meliaceae Family
Authors: Braga Teresa M. , Rocha Lídia , Chung Tsz Yan , Oliveira Rita F. , Pinho Cláudia , Oliveira Ana I. , Morgado Joaquim , Cruz Agostinho
Published: January 2020

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.
Abnormal Cannabidiol Affects Production of Pro-Inflammatory Mediators and Astrocyte Wound Closure in Primary Astrocytic-Microglial Cocultures
Authors: Cardinal von Widdern Julian , Hohmann Tim , Dehghani Faramarz
Published: January 2020

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.
Fragaria Genus: Chemical Composition and Biological Activities
Authors: Fierascu Radu Claudiu , Temocico Georgeta , Fierascu Irina , Ortan Alina , Babeanu Narcisa Elena
Published: January 2020

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.
Non-Volatile Transistor Memory with a Polypeptide Dielectric
Authors: Liang Lijuan , He Wenjuan , Cao Rong , Wei Xianfu , Uemura Sei , Kamata Toshihide , Nakamura Kazuki , Ding Changshuai , Liu Xuying , Kobayashi Norihisa
Published: January 2020

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.
Impacts of Chemical-Assisted Thermal Pretreatments on Methane Production from Fruit and Vegetable Harvesting Wastes: Process Optimization
Authors: Günerhan Ümmihan , Us Ender , Dumlu Lütfiye , Yılmaz Vedat , Carrère Hélène , Perendeci Altınay N.
Published: January 2020

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.
White Matter and Neuroprotection in Alzheimer’s Dementia
Authors: Lorenzini Luca , Fernandez Mercedes , Baldassarro Vito Antonio , Bighinati Andrea , Giuliani Alessandro , Calzà Laura , Giardino Luciana
Published: January 2020

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.
Effectiveness of Different Analytical Methods for the Characterization of Propolis: A Case of Study in Northern Italy
Authors: Pavlovic Radmila , Borgonovo Gigliola , Leoni Valeria , Giupponi Luca , Ceciliani Giulia , Sala Stefano , Bassoli Angela , Giorgi Annamaria
Published: January 2020

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.
Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses
Authors: El Khalki Lamyae , Maire Virginie , Dubois Thierry , Zyad Abdelmajid
Published: January 2020

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.
From Dermal Patch to Implants—Applications of Biocomposites in Living Tissues
Authors: Valente Karolina Papera , Brolo Alexandre , Suleman Afzal
Published: January 2020

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.
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
Authors: Fang Lingling , Yang Tianhong , Medina-Bolivar Fabricio
Published: January 2020

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.
The Effect of Polyphenols on Pomegranate Fruit Susceptibility to Pilidiella granati Provides Insights into Disease Tolerance Mechanisms
Authors: Mincuzzi Annamaria , Ippolito Antonio , Brighenti Virginia , Marchetti Lucia , Benvenuti Stefania , Ligorio Angela , Pellati Federica , Sanzani Simona Marianna
Published: January 2020

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.
Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment
Authors: Liang Jingou , Peng Xinyu , Zhou Xuedong , Zou Jing , Cheng Lei
Published: January 2020

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.
Finger-Temperature-Detecting Liquid Crystal Composite Film for Anti-Counterfeiting Labels
Authors: Gao Yanzi , Feng Ke , Zhang Jin , Zhang Lanying
Published: January 2020

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.
Structural Diversity of Sense and Antisense RNA Hexanucleotide Repeats Associated with ALS and FTLD
Authors: Božič Tim , Zalar Matja , Rogelj Boris , Plavec Janez , Šket Primož
Published: January 2020

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.
Microbial Transformation of Prenylquercetins by Mucor hiemalis
Authors: Han Fubo , Xiao Yina , Lee Ik-Soo
Published: January 2020

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.