bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Prediction of Chiral Iron Complexes for Asymmetric Transfer Hydrogenation of Pyruvic Acid to Lactic Acid
Authors: Wang Wan , Yang Xinzheng
Published: April 2020

Density functional theory calculations reveal a formic acid-assisted proton transfer mechanism for asymmetric transfer hydrogenation of pyruvic acid catalyzed by a chiral Fe complex, FeH[(R,R)-BESNCH(Ph)CH(Ph)NH2](η6-p-cymene), with formic acid as the hydrogen provider. The rate-determining step is the hydride transfer from formate anion to Fe for the formation and dissociation of CO2 with a total free energy barrier of 28.0 kcal mol−1. A series of new bifunctional iron complexes with η6-p-cymene replaced by different arene and sulfonyl groups were built and computationally screened as potential catalysts. Among the proposed complexes, we found 1g with η6-p-cymene replaced by 4-isopropyl biphenyl had the lowest free energy barrier of 26.2 kcal mol−1 and excellent chiral selectivity of 98.5% ee.
A Review of Cytotoxic Plants of the Indian Subcontinent and a Broad-Spectrum Analysis of Their Bioactive Compounds
Authors: Mazumder Kishor , Biswas Biswajit , Raja Iqbal Mahmud , Fukase Koichi
Published: April 2020

Cancer or uncontrolled cell proliferation is a major health issue worldwide and is the second leading cause of deaths globally. The high mortality rate and toxicity associated with cancer chemotherapy or radiation therapy have encouraged the investigation of complementary and alternative treatment methods, such as plant-based drugs. Moreover, over 60% of the anti-cancer drugs are molecules derived from plants or their synthetic derivatives. Therefore, in the present review, an attempt has been made to summarize the cytotoxic plants available in the Indian subcontinent along with a description of their bio-active components. The review covers 99 plants of 57 families as well as over 110 isolated bioactive cytotoxic compounds, amongst which at least 20 are new compounds. Among the reported phytoconstituents, artemisinin, lupeol, curcumin, and quercetin are under clinical trials, while brazilin, catechin, ursolic acid, β-sitosterol, and myricetin are under pharmacokinetic development. However, for the remaining compounds, there is little or no information available. Therefore, further investigations are warranted on these subcontinent medicinal plants as an important source of novel cytotoxic agents.
Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy
Authors: Concepción Odette , Belmar Julio , F. de la Torre Alexander , M. Muñiz Francisco , Pertino Mariano W. , Alarcón Barbara , Ormazabal Valeska , Nova-Lamperti Estefania , Zúñiga Felipe A. , Jiménez Claudio A.
Published: April 2020

Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2–oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.
Gamification as a Methodological Complement to Flipped Learning—An Incident Factor in Learning Improvement
Authors: Pozo Sánchez Santiago , López Belmonte Jesús , Fuentes Cabrera Arturo , López Núñez Juan Antonio
Published: April 2020

Educational innovation is a reality that is present in learning spaces. The use of emerging methodologies such as gamification and flipped learning has shown great potential in improving the teaching and learning process. This study aims to analyze the effectiveness of innovative mixed practices, combining gamification and flipped learning in the subject of Spanish Language and Literature against the isolated use of flipped learning. For this, a quasi-experimental design of descriptive and correlational type, based on a quantitative methodology has been carried out. For its development, two study groups (control-experimental) have been set up. The selected sample is of an intentional nature and was composed of 60 students of the fourth year of Secondary Education of an educational center in Southern Spain. The data has been collected through a validated questionnaire. The results determine that the complement of gamification in flipped learning has led to improvements in various academic indicators. It is concluded that the development of gamified actions in the face-to-face phase of flipped learning improves the motivation, interaction with teachers, and interactions of students.
Magnetron-Sputtered Polytetrafluoroethylene-Stabilized Silver Nanoisland Surface for Surface-Enhanced Fluorescence
Authors: Šubr Martin , Praus Petr , Kuzminova Anna , Kočišová Eva , Kylián Ondřej , Sureau Franck , Procházka Marek , Štěpánek Josef
Published: April 2020

Surface-enhanced fluorescence (SEF) requires the absorption/emission band of the fluorophore, the localized surface plasmon resonance (LSPR) of the nanostructure and the excitation wavelength to fall in the same (or very close) spectral range. In this paper, we monitor the SEF intensity and lifetime dependence of riboflavin (vitamin B2) adsorbed on a spacer-modified Ag substrate with respect to the thickness of the spacer. The substrates were formed by silver nanoislands deposited onto magnetron-sputtered polytetrafluoroethylene (ms-PTFE). The spacer was formed by the ms-PTFE layer with the thickness ranging from ~5 to 25 nm. The riboflavin dissolved in dimethylsulfoxide (DMSO) at a 10 µM concentration forms, at the ms-PTFE surface, a homogeneous layer of adsorbed molecules corresponding to a monomolecular layer. The microspectroscopic measurements of the adsorbed layer were performed through a sessile droplet; our study has shown the advantages and limitations of this approach. Time-resolved fluorescence enabled us to determine the enhanced fluorescence quantum yield due to the shortening of the radiative decay in the vicinity of the plasmonic surface. For the 5 nm ms-PTFE layer possessing the largest (estimated 4×) fluorescence enhancement, the quantum yield was increased 2.3×.
Studies on Sensing Properties and Mechanism of CuO Nanoparticles to H2S Gas
Authors: Peng Fang , Sun Yan , Lu Yue , Yu Weiwei , Ge Meiying , Shi Jichao , Cong Rui , Hao Jiaming , Dai Ning
Published: April 2020

In this work, the high crystalline copper oxide (CuO) nanoparticles were fabricated by a hydrothermal method, and their structural properties were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The sensing results show that CuO nanoparticles exhibit enhanced sensitivity and good selectivity for hydrogen sulfide (H2S) gas at a low temperature. There are two working mechanisms involved in the H2S sensing based on CuO nanoparticle sensors. They are the H2S oxidation mechanism and the copper sulphide (CuS) formation mechanism, respectively. The two sensing mechanisms collectively enhance the sensor’s response in the H2S sensing process. The Cu–S bonding is stable and cannot break spontaneously at a low temperature. Therefore, the CuS formation inhibits the sensor’s recovery process. Such inhibition gradually enhances as the gas concentration increases from 0.2 ppm to 5 ppm, and it becomes weaker as the operating temperature rises from 40 °C to 250 °C. The XPS results confirmed the CuS formation phenomenon, and the micro Raman spectra demonstrated that the formation of CuS bonding and its decomposition can be effectively triggered by a thermal effect. Gas-sensing mechanism analysis supplied abundant cognition for the H2S sensing phenomena based on CuO materials.
A Novel Biocompatible Titanium–Gadolinium Quantum Dot as a Bacterial Detecting Agent with High Antibacterial Activity
Authors: Sur Vishma Pratap , Mazumdar Aninda , Ashrafi Amirmansoor , Mukherjee Atripan , Milosavljevic Vedran , Michalkova Hana , Kopel Pavel , Richtera Lukáš , Moulick Amitava
Published: April 2020

In this study, the titanium–gadolinium quantum dots (TGQDs) were novel, first of its type to be synthesized, and fully characterized to date. Multiple physical characterization includes scanning electron microscopy (SEM), scanning electrochemical microscope (SCEM), x-ray fluorescence, spectrophotometry, and dynamic light scattering were carried out. The obtained results confirmed appropriate size and shape distributions in addition to processing optical features with high quantum yield. The synthesized TGQD was used as a fluorescent dye for bacterial detection and imaging by fluorescent microscopy and spectrophotometry, where TGQD stained only bacterial cells, but not human cells. The significant antibacterial activities of the TGQDs were found against a highly pathogenic bacterium (Staphylococcus aureus) and its antibiotic resistant strains (vancomycin and methicillin resistant Staphylococcus aureus) using growth curve analysis and determination of minimum inhibitory concentration (MIC) analysis. Live/dead cell imaging assay using phase-contrast microscope was performed for further confirmation of the antibacterial activity. Cell wall disruption and release of cell content was observed to be the prime mode of action with the reduction of cellular oxygen demand (OD).
Photocatalytic Reduction of Cr(VI) in the Presence of Humic Acid Using Immobilized Ce–ZrO2 under Visible Light
Authors: Bortot Coelho Fabrício Eduardo , Candelario Victor M. , Araújo Estêvão Magno Rodrigues , Miranda Tânia Lúcia Santos , Magnacca Giuliana
Published: April 2020

Cr(VI) has several industrial applications but it is one of the most dangerous pollutants because of its carcinogenicity and high toxicity. Thus, the removal of Cr(VI) by photocatalytic reduction was investigated. The catalyst applied, Ce–ZrO2, was immobilized, through a sol–gel process on a silicon carbide (SiC) support, to increase the efficiency and avoid using suspended nanoparticles. The influence of initial pH, humic acid (HA), and catalyst dosage was investigated for Cr(VI) containing solutions. Then, a real galvanizing industry effluent (Cr(VI) = 77 mg L-1mg.L−1, Zn = 1789 mg L−1) was treated. It was observed that Cr(VI) adsorption and photoreduction are greatly favored at low pH values. HA can decrease Cr(VI) adsorption but also acts as holes scavenger, reducing the electron–hole recombination, favoring then the photoreduction. With the immobilized Ce–ZrO2, more than 97% of Cr(VI) was removed from the diluted effluent. These results indicate the feasibility to treat Cr(VI) effluents even in the presence of other metals and natural organic matter. The developed material has great chemical and mechanical resistances and avoids the use of nanoparticles, dangerous for the environment and hard to recover. Moreover, solar light can be used to drive the process, which contributes to the development of more sustainable, cleaner, and cost-effective wastewater treatments.
Plasma Enabled Fe2O3/Fe3O4 Nano-aggregates Anchored on Nitrogen-doped Graphene as Anode for Sodium-Ion Batteries
Authors: Wang Qianqian , Ma Yujie , Liu Li , Yao Shuyue , Wu Wenjie , Wang Zhongyue , Lv Peng , Zheng Jiajin , Yu Kehan , Wei Wei , Ostrikov Kostya (Ken)
Published: April 2020

Low electrical conductivity severely limits the application of Fe2O3 in lithium- and sodium-ion batteries. In respect of this, we design and fabricate Fe2O3/Fe3O4 nano-aggregates anchored on nitrogen-doped graphene as an anode for sodium-ion batteries with the assistance of microwave plasma. The highly conductive Fe3O4 in the composite can function as a highway of electron transport, and the voids and phase boundaries in the Fe2O3/Fe3O4 heterostructure facilitate Na+ ion diffusion into the nano-aggregates. Furthermore, the Fe–O–C bonds between the nano-aggregates and graphene not only stabilize the structural integrity, but also enhance the charge transfer. Consequently, the Fe2O3/Fe3O4/NG anode exhibits specific capacity up to 362 mAh g−1 at 100 mA g−1, excellent rate capability, and stable long-term cycling performance. This multi-component-based heterostructure design can be used in anode materials for lithium- and sodium-ion batteries, and potential opens a new path for energy storage electrodes.
Investigating Various Permutations of Copper Iodide/FeCu Tandem Materials as Electrodes for Dye-Sensitized Solar Cells with a Natural Dye
Authors: Alami Abdul Hai , Faraj Mohammed , Aokal Kamilia , Abu Hawili Abdullah , Tawalbeh Muhammad , Zhang Di
Published: April 2020

This work presents the synthesis and deposition of CuI and FeCu materials on copper substrates for dye-sensitized solar cell applications. FeCu is a metastable alloy of iron and copper powders and possesses good optical and intrinsic magnetic properties. Coupled with copper iodide as tandem layers, the deposition of these two materials was permutated over a pure copper substrate, characterized and then tested within a solar cell. The cell was sensitized with a natural dye extracted from a local desert plant (Calotropis gigantea) and operated with an iodine/triiodide electrolyte. The results show that the best layer arrangement was Cu/FeCu/CuI, which gave an efficiency of around 0.763% (compared to 0.196% from reported cells in the literature using a natural sensitizer).
Emerging Nano- and Micro-Technologies Used in the Treatment of Type-1 Diabetes
Authors: Primavera Rosita , Kevadiya Bhavesh D , Swaminathan Ganesh , Wilson Rudilyn Joyce , De Pascale Angelo , Decuzzi Paolo , Thakor Avnesh S
Published: April 2020

Type-1 diabetes is characterized by high blood glucose levels due to a failure of insulin secretion from beta cells within pancreatic islets. Current treatment strategies consist of multiple, daily injections of insulin or transplantation of either the whole pancreas or isolated pancreatic islets. While there are different forms of insulin with tunable pharmacokinetics (fast, intermediate, and long-acting), improper dosing continues to be a major limitation often leading to complications resulting from hyper- or hypo-glycemia. Glucose-responsive insulin delivery systems, consisting of a glucose sensor connected to an insulin infusion pump, have improved dosing but they still suffer from inaccurate feedback, biofouling and poor patient compliance. Islet transplantation is a promising strategy but requires multiple donors per patient and post-transplantation islet survival is impaired by inflammation and suboptimal revascularization. This review discusses how nano- and micro-technologies, as well as tissue engineering approaches, can overcome many of these challenges and help contribute to an artificial pancreas-like system.
Study of Silicon Nitride Inner Spacer Formation in Process of Gate-all-around Nano-Transistors
Authors: Li Junjie , Li Yongliang , Zhou Na , Xiong Wenjuan , Wang Guilei , Zhang Qingzhu , Du Anyan , Gao Jianfeng , Kong Zhenzhen , Lin Hongxiao , Xiang Jinjuan , Li Chen , Yin Xiaogen , Wang Xiaolei , Yang Hong , Ma Xueli , Han Jianghao , Zhang Jing , Hu Tairan , Cao Zhe , Yang Tao , Li Junfeng , Yin Huaxiang , Zhu Huilong , Luo Jun , Wang Wenwu , Radamson Henry H.
Published: April 2020

Stacked SiGe/Si structures are widely used as the units for gate-all-around nanowire transistors (GAA NWTs) which are a promising candidate beyond fin field effective transistors (FinFETs) technologies in near future. These structures deal with a several challenges brought by the shrinking of device dimensions. The preparation of inner spacers is one of the most critical processes for GAA nano-scale transistors. This study focuses on two key processes: inner spacer film conformal deposition and accurate etching. The results show that low pressure chemical vapor deposition (LPCVD) silicon nitride has a good film filling effect; a precise and controllable silicon nitride inner spacer structure is prepared by using an inductively coupled plasma (ICP) tool and a new gas mixtures of CH2F2/CH4/O2/Ar. Silicon nitride inner spacer etch has a high etch selectivity ratio, exceeding 100:1 to Si and more than 30:1 to SiO2. High anisotropy with an excellent vertical/lateral etch ratio exceeding 80:1 is successfully demonstrated. It also provides a solution to the key process challenges of nano-transistors beyond 5 nm node.
Enhanced Solar Light Photocatalytic Activity of Ag Doped TiO2–Ag3PO4 Composites
Authors: Hamrouni Abdessalem , Azzouzi Hanen , Rayes Ali , Palmisano Leonardo , Ceccato Riccardo , Parrino Francesco
Published: April 2020

Composites comprised of Ag3PO4 and bare TiO2 (TiO2@Ag3PO4) or silver doped TiO2 (Ag@TiO2–Ag3PO4) have been synthesized by coupling sol–gel and precipitation methods. For the sake of comparison, also the bare components have been similarly prepared. All the samples have been characterized by X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR), photoelectrochemical measurements, and specific surface area (SSA) analysis. The optoelectronic and structural features of the samples have been related to their photocatalytic activity for the degradation of 4–nitrophenol under solar and UV light irradiation. Coupling Ag3PO4 with silver doped TiO2 mitigates photocorrosion of the Ag3PO4 counterpart, and remarkably improves the photocatalytic activity under solar light irradiation with respect to the components, to the TiO2–Ag3PO4 sample, and to the benchmark TiO2 Evonik P25. These features open the route to future applications of this material in the field of environmental remediation.
Short-Communication: Ingestion of a Nucleotide-Rich Mixed Meal Increases Serum Uric Acid Concentrations but Does Not Affect Postprandial Blood Glucose or Serum Insulin Responses in Young Adults
Authors: Coelho Mariana O. C. , Monteyne Alistair J. , Kamalanathan Ishara D. , Najdanovic-Visak Vesna , Finnigan Tim J. A. , Stephens Francis B. , Wall Benjamin T.
Published: April 2020

Circulating uric acid concentrations have been linked to various metabolic diseases. Consumption of large boluses of nucleotides increases serum uric acid concentrations. We investigated the effect of a nucleotide-rich mixed meal on postprandial circulating uric acid, glucose, and insulin responses. Ten healthy adults participated in a randomised, controlled, double-blind, crossover trial in which they consumed a mixed-meal containing either nucleotide-depleted mycoprotein (L-NU) or high-nucleotide mycoprotein (H-NU) on two separate visits. Blood samples were collected in the postabsorptive state and throughout a 24 h postprandial period, and were used to determine circulating uric acid, glucose, and insulin concentrations. Mixed meal ingestion had divergent effects on serum uric acid concentrations across conditions (time x condition interaction; P < 0.001), with L-NU decreasing transiently (from 45 to 240 min postprandially) by ~7% (from 279 ± 16 to 257 ± 14 µmol·L−1) and H-NU resulting in a ~12% increase (from 284 ± 13 to 319 ± 12 µmol·L−1 after 210 min), remaining elevated for 12 h and returning to baseline concentrations after 24 h. There were no differences between conditions in blood glucose or serum insulin responses, nor in indices of insulin sensitivity. The ingestion of a nucleotide-rich mixed-meal increases serum uric acid concentrations for ~12 h, but does not influence postprandial blood glucose or serum insulin concentrations.
Urinary Metabolic Profiling via LC-MS/MS Reveals Impact of Bovine Lactoferrin on Bone Formation in Growing SD Rats
Authors: Xu Yan , Zhao Tianyu , Ren Haowei , Xie Yindan , An Jingjing , Shang Jiaqi , Tabys Dina , Liu Ning
Published: April 2020

Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person’s correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.
Effects of Acute Dietary Polyphenols and Post-Meal Physical Activity on Postprandial Metabolism in Adults with Features of the Metabolic Syndrome
Authors: Davis Dustin W , Navalta James W , McGinnis Graham R , Serafica Reimund , Izuora Kenneth , Basu Arpita
Published: April 2020

Approximately 22% of U.S. adults and 25% of adults globally have metabolic syndrome (MetS). Key features, such as dysglycemia and dyslipidemia, predict type 2 diabetes, cardiovascular disease, premature disability, and death. Acute supplementation of dietary polyphenols and post-meal physical activity hold promise in improving postprandial dysmetabolism. To our knowledge, no published review has described the effects of either intervention on postprandial glucose, insulin, lipids, and markers of oxidative damage and inflammation in adults with features of MetS. Thus, we conducted this review of controlled clinical trials that provided dietary polyphenols from oils, fruits, teas, and legumes during a dietary challenge, or implemented walking, cycling, and stair climbing and descending after a dietary challenge. Clinical trials were identified using ClinicalTrials.gov, PubMed, and Google Scholar and were published between 2000 and 2019. Dietary polyphenols from extra virgin olive oil, grapes, blackcurrants, strawberries, black tea, and black beans improved postprandial glucose, insulin, and markers of oxidative damage and inflammation, but results were not consistent among clinical trials. Freeze-dried strawberry powder distinctly improved postprandial insulin and markers of oxidative damage and inflammation. Post-meal physical activity attenuated postprandial glucose, but effects on postprandial lipids and markers of oxidative damage and inflammation were inconclusive. Consuming dietary polyphenols with a meal and completing physical activity after a meal may mitigate postprandial dysmetabolism in adults with features of MetS.
Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose–Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data
Authors: Furihata Kei , Tsuchikawa Masaru , Miwa Takaki , Naito Yuji , Oba Koji , Sakagami Masafumi
Published: April 2020

Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose–response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 µg/dL (95% confidence interval: 5.46, 12.70; heterogeneity: I 2 = 0.61%) compared to the placebo. A significant dose–response relationship was confirmed (p < 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose–response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 µg/dL, and 150 mg for 70 µg/dL or more.
Sturgeon (Acipenser)-Derived Chondroitin Sulfate Suppresses Human Colon Cancer HCT-116 Both In Vitro and In Vivo by Inhibiting Proliferation and Inducing Apoptosis
Authors: Wu Ruiyun , Shang Nan , Gui Meng , Yin Jian , Li Pinglan
Published: April 2020

Chondroitin sulfate (CS), mainly present in the cartilage and bone of animals, is known as a potential food-derived bioactive that has several biological functions, such as anti-arthritic and anti-inflammatory activity. Sturgeon (Acipenser), an important fishery resource in China, contains an abundance of CS in their cartilage. In our previous study, we have extracted and purified CS from sturgeon cartilage. Herein, we further investigate the health benefits of sturgeon-derived chondroitin sulfate (SCS), especially for colorectal cancer treatment. The in vitro study indicated that SCS could inhibit the proliferation of the human colon cancer cell line HCT-116 in a dose-dependent manner, which was associated with cell cycle arrest. In addition, SCS also led to extensive cellular apoptosis in colon cancer cell HCT-116 cells. Meanwhile, an in vivo study showed that SCS treatment significantly inhibited the tumor development of xenograft HCT-116 in mice via proliferation suppression and apoptosis induction. Further, a mechanistic study demonstrated that the apoptosis induction was mainly due to the activation of the Bcl-2 family-associated mitochondrial pathway. Overall, our results provided a basis for SCS as a promising agent against colon cancer.
Nutrition in Patients with Idiopathic Pulmonary Fibrosis: Critical Issues Analysis and Future Research Directions
Authors: Faverio Paola , Bocchino Marialuisa , Caminati Antonella , Fumagalli Alessia , Gasbarra Monica , Iovino Paola , Petruzzi Alessandra , Scalfi Luca , Sebastiani Alfredo , Stanziola Anna Agnese , Sanduzzi Alessandro
Published: April 2020

In idiopathic pulmonary fibrosis (IPF), several factors may have a negative impact on the nutritional status, including an increased respiratory muscles load, release of inflammation mediators, the coexistence of hypoxemia, and physical inactivity. Nutritional abnormalities also have an impact on IPF clinical outcomes. Given the relevance of nutritional status in IPF patients, we sought to focus on some critical issues, highlighting what is known and what should be further learned about these issues. We revised scientific literature published between 1995 and August 2019 by searching on Medline/PubMed and EMBASE databases including observational and interventional studies. We conducted a narrative review on nutritional assessment in IPF, underlining the importance of nutritional evaluation not only in the diagnostic process, but also during follow-up. We also highlighted the need to keep a high level of attention on cardiovascular comorbidities. We also focused on current clinical treatment in IPF with Nintedanib and Pirfenidone and management of gastrointestinal adverse events, such as diarrhea, induced by these antifibrotic drugs. Finally, we concentrated on the importance of pulmonary rehabilitation program, including nutritional assessment, education and behavioral change, and psychological support among its essential components. More attention should be devoted to the assessment of the undernutrition and overnutrition, as well as of muscle strength and physical performance in IPF patients, taking also into account that an adequate clinical management of gastrointestinal complications makes IPF drug treatments more feasible.
Key Vitamin D Target Genes with Functions in the Immune System
Authors: Koivisto Oona , Hanel Andrea , Carlberg Carsten
Published: April 2020

The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.
Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as Radioprotector
Authors: González Aránzazu , Atienza Violeta , Montoro Alegría , Soriano Jose M.
Published: April 2020

For millennia, naturopaths and physicians have used Ganoderma lucidum (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of G. lucidum, or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of G. lucidum aqueous extracts of polysaccharides and triterpenes in mice exposed to γ-rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of β-glucan of aqueous extract of G. lucidum, nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.
Exercise Training Combined with Bifidobacterium longum OLP-01 Supplementation Improves Exercise Physiological Adaption and Performance
Authors: Huang Wen-Ching , Hsu Yi-Ju , Huang Chi-Chang , Liu Hsuan-Chen , Lee Mon-Chien
Published: April 2020

Probiotics exert multiple health benefits, including gastrointestinal health, immunoregulation, and metabolic disease improvement, by modulating microbiota to maintain eubiosis via the hypothalamic–pituitary–adrenal (HPA) and brain–gut–microbiome axes. Physiological fatigue, mental stress, and gastrointestinal discomfort under the demands of athletic performance as well as immunosuppression are common during endurance training and competition. Limited studies investigated the functional effects of probiotic supplementation on endurance training. Bifidobacterium longum subsp. Longum OLP-01 (OLP-01), isolated from an elite Olympic athlete, was combined with a six-week exercise training program with gradually increasing intensity. In this study, Institute of Cancer Research (ICR) mice were assigned to sedentary, exercise, OLP-01, or exercise + OLP-01 groups and administered probiotic and/or treadmill exercise training for six weeks to assess exercise performance, physiological adaption, and related metabolites. The exercise + OLP-01 group demonstrated higher performance in terms of endurance and grip strength, as well as improved fatigue-associated indexes (lactate, ammonia, creatine kinase (CK), lactate dehydrogenase (LDH), and glycogen content), compared with the other groups. OLP-01 supplementation significantly ameliorated inflammation and injury indexes (platelet/lymphocyte ratio (PLR), aminotransferase (AST), and CK) caused by prolonged endurance exercise test. Moreover, acetate, propionate, and butyrate levels were significantly higher in the exercise + OLP-01 group than in the sedentary and OLP-01 groups. Athletes often experience psychological and physiological stress caused by programed intensive exercise, competition, and off-site training, often leading to poor exercise performance and gastrointestinal issues. Functional OLP-01 probiotics are considered to be a nutritional strategy for improving physiological adaption, oxidative stress, inflammation, and energy balance to ensure high physical performance. Based on these results, probiotics combined with exercise training is a potential strategy for ensuring high physical performance of athletes, which should be further investigated through microbiota validation.
Natural Protein Tolerance and Metabolic Control in Patients with Hereditary Tyrosinaemia Type 1
Authors: Yilmaz Ozlem , Daly Anne , Pinto Alex , Ashmore Catherine , Evans Sharon , Gupte Girish , Santra Saikat , Preece Mary Anne , Mckiernan Patrick , Kitchen Steve , Yabanci Ayhan Nurcan , MacDonald Anita
Published: April 2020

In a longitudinal retrospective study, we aimed to assess natural protein (NP) tolerance and metabolic control in a cohort of 20 Hereditary Tyrosinaemia type I (HTI) patients. Their median age was 12 years ([3.2–17.7 years], n = 11 female, n = 8 Caucasian, n = 8 Asian origin, n = 2 Arabic and n = 2 Indian). All were on nitisinone (NTBC) with a median dose of 0.7 g/kg/day (range 0.4–1.5 g/kg/day) and were prescribed a tyrosine (Tyr)/phenylalanine (Phe)-restricted diet supplemented with Tyr/Phe-free L-amino acids. Data were collected on clinical signs at presentation, medical history, annual dietary prescriptions, and blood Phe and Tyr levels from diagnosis until transition to the adult service (aged 16–18 years) or liver transplantation (if it preceded transition). The median age of diagnosis was 2 months (range: 0 to 24 months), with n = 1 diagnosed by newborn screening, n = 3 following phenylketonuria (PKU) screening and n = 7 by sibling screening. Five patients were transplanted (median age 6.3 years), and one died due to liver cancer. The median follow-up was 10 years (3–16 years), and daily prescribed NP intake increased from a median of 5 to 24 g/day. Lifetime median blood Tyr (370 µmol/L, range 280–420 µmol/L) and Phe (50 µmol/L, 45–70 µmol/L) were maintained within the target recommended ranges. This cohort of HTI patients were able to increase the daily NP intake with age while maintaining good metabolic control. Extra NP may improve lifelong adherence to the diet.
A Mediterranean Diet Is Positively Associated with Bone and Muscle Health in a Non-Mediterranean Region in 25,450 Men and Women from EPIC-Norfolk
Authors: Jennings Amy , Mulligan Angela A. , Khaw Kay-Tee , Luben Robert N. , Welch Ailsa A.
Published: April 2020

Research on Mediterranean diet (MD) adherence and musculoskeletal health is limited. The current study determined if adherence to the alternative MD score (aMED) and MD score (MDS), quantified from 7-d food diaries, was associated with fracture incidence, bone density (calcaneal broadband ultrasound attenuation (BUA)) and fat free mass (expressed over BMI (FFMBMI) using bioelectrical impedance) in 25,450 men and women recruited to the European Prospective Investigation into Cancer study in Norfolk, UK. During 17.4 years of follow up (443,178 total person years) 2195 incident fractures occurred. Higher aMED adherence was associated with 23% reduced total (Q5–Q1 HR 0.77; 95% CI 0.67, 0.88; p-trend < 0.01) and 21% reduced hip (Q5–Q1 HR 0.79; 95% CI 0.65, 0.96; p-trend = 0.01) fracture incidence, and significantly higher BUA (Q5–Q1 1.0 dB/MHz 95% CI 0.2, 1.9; p-trend < 0.01) and FFMBMI (Q5–Q1 0.05 kg/(kg/m2) 95% CI 0.04, 0.06; p-trend < 0.01), comparing extreme adherence quintiles. Higher MDS was also associated with reduced total fractures (Q5–Q1 HR 0.83; 95% CI 0.71, 0.96; p-trend = 0.03) and significantly higher BUA (Q5–Q1 1.4 dB/MHz 95% CI 0.5, 2.3; p-trend < 0.01) and FFMBMI (Q5–Q1 0.03 kg/(kg/m2) 95% CI 0.01, 0.04; p-trend < 0.01). This evidence supports the need to develop interventions to enhance MD adherence, particularly in women, where evidence for associations was stronger.
Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins
Authors: Lo Cigno Irene , Calati Federica , Albertini Silvia , Gariglio Marisa
Published: April 2020

The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition reactivates the host innate immune response, reversing what until then was an unresponsive cellular state suitable for viral persistence and tumorigenesis. Given that the disruption of distinct mechanisms of immune evasion is an attractive strategy for cancer therapy, the race is on to gain a better understanding of E6/E7-induced immune escape and cancer progression. Here, we review recent literature on the interplay between E6/E7 and the innate immune signaling pathways cGAS/STING/TBK1, RIG-I/MAVS/TBK1, and Toll-like receptors (TLRs). The overall emerging picture is that E6 and E7 have evolved broad-spectrum mechanisms allowing for the simultaneous depletion of multiple rather than single innate immunity effectors. The cGAS/STING/TBK1 pathway appears to be the most heavily impacted, whereas the RIG-I/MAVS/TBK1, still partially functional in HPV-transformed cells, can be activated by the powerful RIG-I agonist M8, triggering the massive production of type I and III interferons (IFNs), which potentiates chemotherapy-mediated cell killing. Overall, the identification of novel therapeutic targets to restore the innate immune response in HPV-transformed cells could transform the way HPV-associated cancers are treated.
Impact of Bacteriophage-Supplemented Drinking Water on the E. coli Population in the Chicken Gut
Authors: Kittler Sophie , Mengden Ruth , Korf Imke H. E. , Bierbrodt Anna , Wittmann Johannes , Plötz Madeleine , Jung Arne , Lehnherr Tatiana , Rohde Christine , Lehnherr Hansjörg , Klein Günter , Kehrenberg Corinna
Published: April 2020

Among intestinal coliform microbes in the broiler gut, there are potentially pathogenic Escherichia (E.) coli that can cause avian colibacillosis. The treatment with antibiotics favors the selection of multidrug-resistant bacteria and an alternative to this treatment is urgently required. A chicken model of intestinal colonization with an apathogenic model strain of E. coli was used to test if oral phage application can prevent or reduce the gut colonization of extraintestinal pathogenic E. coli variants in two individual experiments. The E. coli strain E28 was used as a model strain, which could be differentiated from other E. coli strains colonizing the broiler gut, and was susceptible to all cocktail phages applied. In the first trial, a mixture of six phages was continuously applied via drinking water. No reduction of the model E. coli strain E28 occurred, but phage replication could be demonstrated. In the second trial, the applied mixture was limited to the four phages, which showed highest efficacy in vitro. E. coli colonization was reduced in this trial, but again, no reduction of the E. coli strain E28 was observed. The results of the trials presented here can improve the understanding of the effect of phages on single strains in the multi-strain microbiota of the chicken gut.
Human Papillomaviruses and Epstein–Barr Virus Interactions in Colorectal Cancer: A Brief Review
Authors: Fernandes Queenie , Gupta Ishita , Vranic Semir , Al Moustafa Ala-Eddin
Published: April 2020

Human papillomaviruses (HPVs) and the Epstein–Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%–15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis.
Molecular Characterization and Antimicrobial Susceptibility of C. jejuni Isolates from Italian Wild Bird Populations
Authors: Marotta Francesca , Janowicz Anna , Di Marcantonio Lisa , Ercole Claudia , Di Donato Guido , Garofolo Giuliano , Di Giannatale Elisabetta
Published: April 2020

Poultry is considered a major reservoir of human campylobacteriosis. It also been reported that not only poultry, but also wild birds, are capable of carrying C. jejuni, thus demonstrating to be a risk of spreading the bacteria in the environment. To gain insight into the population structure and investigate the antimicrobial resistance genotypes and phenotypes, we analyzed a collection of 135 C. jejuni from 15 species of wild birds in Italy. MLST revealed the presence of 41 sequence types (STs) and 13 clonal complexes (CCs). ST-179 complex and the generalist ST-45 complex were the most prevalent. Core genome MLST revealed that C. jejuni from ST-45 complex clustered according to the bird species, unlike the ST-179 complex which featured 3 different species in the same cluster. Overall we found a moderate prevalence of resistance to tetracycline (12.5%), ciprofloxacin and nalidixic acid (10%). The novel ST isolated from one pigeon showed resistance to all the antibiotics tested. The ST-179 complex (33.3%) was identified with significantly higher nalidixic acid resistance relative to other tested STs. Nine AMR genes (tet(O), cmeA, cmeB, cmeC, cmeR, aad, blaOXA-61, blaOXA-184 and erm(B)) and 23S rRNA and gyrA-associated point mutations were also described, indicating a concordance level between genotypic and phenotypic resistance of 23.3%, 23.4% and of 37.5% for streptomycin, tetracycline and quinolones/fluoroquinolones, respectively. We recommend that particular attention should be given to wild birds as key sentinel animals for the ecosystem contamination surveillance.
Electroanalysis Applied to Compatibility and Stability Assays of Drugs: Carvedilol Study Case
Authors: de Carvalho Murilo Ferreira , Garcia Luane Ferreira , de Macedo Isaac Yves Lopes , Marreto Ricardo Neves , de Oliveira Mayk Teles , do Couto Renê Oliveira , da Cunha Carlos Eduardo Peixoto , de Siqueira Leite Karla Carneiro , Rezende Kênnia Rocha , Machado Fabio Bahls , Somerset Vernon , Gil Eric de Souza
Published: April 2020

Carvedilol (CRV) is a non-selective blocker of α and β adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions.
Targeting the Tumor Microenvironment with Fluorescence-Activatable Bispecific Endoglin/Fibroblast Activation Protein Targeting Liposomes
Authors: Tansi Felista L. , Rüger Ronny , Kollmeier Ansgar M. , Rabenhold Markus , Steiniger Frank , Kontermann Roland E. , Teichgräber Ulf K. , Fahr Alfred , Hilger Ingrid
Published: April 2020

Liposomes are biocompatible nanocarriers with promising features for targeted delivery of contrast agents and drugs into the tumor microenvironment, for imaging and therapy purposes. Liposome-based simultaneous targeting of tumor associated fibroblast and the vasculature is promising, but the heterogeneity of tumors entails a thorough validation of suitable markers for targeted delivery. Thus, we elucidated the potential of bispecific liposomes targeting the fibroblast activation protein (FAP) on tumor stromal fibroblasts, together with endoglin which is overexpressed on tumor neovascular cells and some neoplastic cells. Fluorescence-quenched liposomes were prepared by hydrating a lipid film with a high concentration of the self-quenching near-infrared fluorescent dye, DY-676-COOH, to enable fluorescence detection exclusively upon liposomal degradation and subsequent activation. A non-quenched green fluorescent phospholipid was embedded in the liposomal surface to fluorescence-track intact liposomes. FAP- and murine endoglin-specific single chain antibody fragments were coupled to the liposomal surface, and the liposomal potentials validated in tumor cells and mice models. The bispecific liposomes revealed strong fluorescence quenching, activatability, and selectivity for target cells and delivered the encapsulated dye selectively into tumor vessels and tumor associated fibroblasts in xenografted mice models and enabled their fluorescence imaging. Furthermore, detection of swollen lymph nodes during intra-operative simulations was possible. Thus, the bispecific liposomes have potentials for targeted delivery into the tumor microenvironment and for image-guided surgery.