bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralogical and Geochemical Characterization of Gold Mining Tailings and Their Potential to Generate Acid Mine Drainage (Minas Gerais, Brazil)
Authors: Lemos Mariana , Valente Teresa , Reis Paula Marinho , Fonseca Rita , Delbem Itamar , Ventura Juliana , Magalhães Marcus
Published: December 2020

For more than 30 years, sulfide gold ores were treated in metallurgic plants located in Nova Lima, Minas Gerais, Brazil, and accumulated in the Cocoruto tailings dam. Both flotation and leaching tailings from a deactivated circuit, as well as roasted and leaching tailings from an ongoing plant, were studied for their acid mine drainage potential and elements’ mobility. Detailed characterization of both tailings types indicates the presence of fine-grain size material hosting substantial amounts of sulfides that exhibit distinct geochemical and mineralogical characteristics. The samples from the ongoing plant show high grades of Fe in the form of oxides, cyanide, and sulfates. Differently, samples from the old circuit shave higher average concentrations of Al (0.88%), Ca (2.4%), Mg (0.96%), and Mn (0.17%), present as silicates and carbonates. These samples also show relics of preserved sulfides, such as pyrite and pyrrhotite. Concentrations of Zn, Cu, Au, and As are higher in the tailings of the ongoing circuit, while Cr and Hg stand out in the tailings of the deactivated circuit. Although the obtained results show that the sulfide wastes do not tend to generate acid mine drainage, leaching tests indicate the possibility of mobilization of toxic elements, namely As and Mn in the old circuit, and Sb, As, Fe, Ni, and Se in the tailings of the plant that still works. This work highlights the need for proper management and control of tailing dams even in alkaline drainage environments such as the one of the Cocoruto dam. Furthermore, strong knowledge of the tailings’ dynamics in terms of geochemistry and mineralogy would be pivotal to support long-term decisions on wastes management and disposal.
Uranium Rhizofiltration by Lactuca sativa, Brassica campestris L., Raphanus sativus L., Oenanthe javanica under Different Hydroponic Conditions
Authors: Han Yikyeong , Lee Juyeon , Kim Changmin , Park Jinyoung , Lee Minhee , Yang Minjune
Published: December 2020

Rhizofiltration experiments were conducted using uranium-contaminated groundwater and lettuce (Lactuca sativa), Chinese cabbage (Brassica campestris L.), radish (Raphanus sativus L.), and buttercup (Oenanthe javanica), which are commonly grown and consumed in South Korea. The results of the rhizofiltration experiments with artificial solutions with different initial uranium concentrations (18, 32, 84, 116, 173, and 263 μg/L) show that the uranium accumulation and bioconcentration factor (BCF) of plant roots increase with increasing uranium concentration in the groundwater. Among the four plants, the uranium concentration in the roots of Raphanus sativus L. is 1215.8 μg/g dry weight, with a maximum BCF value of 2692.7. The BCF value of the artificial solutions with various pH values (pH 3, 5, 7, and 9) is the highest under acidic conditions (pH 3) for all four plants. The uranium BCF values based on different hydroponic conditions range from 170.5 to 11580.3 and the results are comparable with those of other studies using similar methods; the highest BCF value was determined for Brassica campestris L. at pH 3. The BCF values of Raphanus sativus L. after the rhizofiltration experiments with genuine groundwater contaminated with uranium are the highest among the four species; that is, 1684.7 and 1700.1 in Oesam-dong and Bugokdong groundwater samples with uranium concentrations of 83 and 173 μg/L, respectively. The results of the scanning electron microscope/electron dispersive X-ray spectroscope analyses show that uranium in contaminated groundwater is adsorbed as a solid phase on the root surface. These results demonstrate that Raphanus sativus L. has a high tolerance to high concentrations of uranium and low pH conditions and a remarkable potential for uranium accumulation.
Wild Plants for the Phytostabilization of Phosphate Mine Waste in Semi-Arid Environments: A Field Experiment
Authors: Zine Hamza , Elgadi Sara , Hakkou Rachid , Papazoglou Eleni , Midhat Laila , Ouhammou Ahmed
Published: December 2020

The management of mine waste has become an urgent issue, especially in semi-arid environments. In this context, and with an aim to inhibit the oxidation of the sulfide tailings of the abandoned mine of Kettara in Morocco, a store-and-release (SR) cover made of phosphate mine waste (PW) was implemented. In order to guarantee its long-term performance, phytostabilization by local wild plant species is currently the most effective and sustainable solution. This study aimed to assess the growth performance and phytostabilization efficiency of five local wild plant species to grow on the SR cover made of PW. A field experiment was conducted for two growing seasons (2018 and 2019), without amendments and with the minimum of human care. PW and the aboveground and belowground parts of the studied plant species were collected and analyzed for As, Cd, Cu, Ni, and Zn. The bioconcentration factor (BCF) and translocation factor (TF) were also calculated. Despite the hostile conditions of the mining environment, the five plant species showed promising growth performances as follows: Atriplex semibaccata > Vicia sativa > Launaea arborescens > Peganum harmala > Asparagus horridus. The five plants showed high accumulation capacity of the trace elements, with the highest concentrations in belowground tissue. Principal component analysis distinguished A. semibaccata as having a high concentration of Cu and As, while Asparagus horridus had higher concentrations of Cd and Zn. In contrast, P. harmala, V. sativa, and L. arborescens demonstrated affinity regarding Ni. According to the BCF (<1) and TF (<1), these plant species could be used as effective phytostabilizers of the studied trace elements. The present study showed that local wild plant species have a great potential for the phytostabilization of PW, and could ensure the long-term efficiency of SR cover.
Hydrodechlorination of 4-Chlorophenol on Pd-Fe Catalysts on Mesoporous ZrO2SiO2 Support
Authors: Lokteva Ekaterina S. , Shishova Vera V. , Tolkachev Nikolay N. , Kharlanov Andrey N. , Maslakov Konstantin I. , Kamaev Alexey O. , Kaplin Igor Yu. , Savina Irina N. , Golubina Elena V.
Published: December 2020

A mesoporous support based on silica and zirconia (ZS) was used to prepare monometallic 1 wt% Pd/ZS, 10 wt% Fe/ZS, and bimetallic FePd/ZS catalysts. The catalysts were characterized by TPR-H2, XRD, SEM-EDS, TEM, AAS, and DRIFT spectroscopy of adsorbed CO after H2 reduction in situ and tested in hydrodechlorination of environmental pollutant 4-chlorophelol in aqueous solution at 30 °C. The bimetallic catalyst demonstrated an excellent activity, selectivity to phenol and stability in 10 consecutive runs. FePd/ZS has exceptional reducibility due to the high dispersion of palladium and strong interaction between FeOx and palladium, confirmed by TPR-H2, DRIFT spectroscopy, XRD, and TEM. Its reduction occurs during short-time treatment with hydrogen in an aqueous solution at RT. The Pd/ZS was more resistant to reduction but can be activated by aqueous phenol solution and H2. The study by DRIFT spectroscopy of CO adsorbed on Pd/ZS reduced in harsh (H2, 330 °C), medium (H2, 200 °C) and mild conditions (H2 + aqueous solution of phenol) helped to identify the reasons of the reducing action of phenol solution. It was found that phenol provided fast transformation of Pd+ to Pd0. Pd/ZS also can serve as an active and stable catalyst for 4-PhCl transformation to phenol after proper reduction.
Geissospermiculatine, a New Alkaloid from Geissospermum reticulatum Bark
Authors: Sajkowska-Kozielewicz Joanna J. , Kozielewicz Paweł , Makarova Katerina , Stocki Marcin , Barnes Nicholas M. , Paradowska Katarzyna
Published: December 2020

A new alkaloid, geissospermiculatine was characterized in Geissospermum reticulatum A. H. Gentry bark (Apocynaceae). Here, following a simplified isolation protocol, the structure of the alkaloid was elucidated through GC-MS, LC-MS/MS, 1D, and 2D NMR (COSY, ROESY, HSQC, HMBC, 1H-15N HMBC). Cytotoxic properties were evaluated in vitro on malignant THP-1 cells, and the results demonstrated that the cytotoxicity of the alkaloid (30  μg/mL) was comparable with staurosporine (10  μM). Additionally, the toxicity was tested on zebrafish (Danio rerio) embryos in vivo by monitoring their development (0–72 h); toxicity was not evident at 30  μg/mL.
Exhaled Breath and Oxygenator Sweep Gas Propionaldehyde in Acute Respiratory Distress Syndrome
Authors: Meidert Agnes S. , Choukèr Alexander , Praun Siegfried , Schelling Gustav , Dolch Michael E.
Published: December 2020

Background: Oxidative stress-induced lipid peroxidation (LPO) due to neutrophil-derived reactive oxygen species plays a key role in the early stage of the acute respiratory distress syndrome (ARDS). Monitoring of oxidative stress in this patient population is of great interest, and, ideally, this can be done noninvasively. Recently, propionaldehyde, a volatile chemical compound (VOC) released during LPO, was identified in the breath of lung transplant recipients as a marker of oxidative stress. The aim of the present study was to identify if markers of oxidative stress appear in the oxygenator outflow gas of patients with severe ARDS treated with veno-venous extracorporeal membrane oxygenation (ECMO). Methods: The present study included patients with severe ARDS treated with veno-venous ECMO. Concentrations of acetone, isoprene, and propionaldehyde were measured in inspiratory air, exhaled breath, and oxygenator inflow and outflow gas at corresponding time points. Ion-molecule reaction mass spectrometry was used to measure VOCs in a sequential order within the first 24 h and on day three after ECMO initiation. Results: Nine patients (5 female, 4 male; age = 42.1 ± 12.2 year) with ARDS and already established ECMO therapy (pre-ECMO PaO2/FiO2 = 44.0 ± 11.5 mmHg) were included into analysis. VOCs appeared in comparable amounts in breath and oxygenator outflow gas (acetone: 838 (422–7632) vs. 1114 (501–4916) ppbv; isoprene: 53.7 (19.5–244) vs. 48.7 (37.9–108) ppbv; propionaldehyde: 53.7 (32.1–82.2) vs. 42.9 (24.8–122) ppbv). Concentrations of acetone, isoprene, and propionaldehyde in breath and oxygenator outflow gas showed a parallel course with time. Conclusions: Acetone, isoprene, and propionaldehyde appear in breath and oxygenator outflow gas in comparable amounts. This allows for the measurement of these VOCs in a critically ill patient population via the ECMO oxygenator outflow gas without the need of ventilator circuit manipulation.
Improved Synthesis of Phosphoramidite-Protected N6-Methyladenosine via BOP-Mediated SNAr Reaction
Authors: Shishodia Shifali , Schofield Christopher J.
Published: December 2020

N6-methyladenosine(m6A) is the most abundant modification in mRNA. Studies on proteins that introduce and bind m6A require the efficient synthesis of oligonucleotides containing m6A. We report an improved five-step synthesis of the m6A phosphoramidite starting from inosine, utilising a 1-H-benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)-mediated SNAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.
Bee Venom in Wound Healing
Authors: Kurek-Górecka Anna , Komosinska-Vassev Katarzyna , Rzepecka-Stojko Anna , Olczyk Paweł
Published: December 2020

Bee venom (BV), also known as api-toxin, is widely used in the treatment of different inflammatory diseases such as rheumatoid arthritis or multiple sclerosis. It is also known that BV can improve the wound healing process. BV plays a crucial role in the modulation of the different phases of wound repair. It possesses anti-inflammatory, antioxidant, antifungal, antiviral, antimicrobial and analgesic properties, all of which have a positive impact on the wound healing process. The mentioned process consists of four phases, i.e., hemostasis, inflammation, proliferation and remodeling. The impaired wound healing process constitutes a significant problem especially in diabetic patients, due to hypoxia state. It had been found that BV accelerated the wound healing in diabetic patients as well as in laboratory animals by impairing the caspase-3, caspase-8 and caspase-9 activity. Moreover, the activity of BV in wound healing is associated with regulating the expression of transforming growth factor (TGF-β1), vascular endothelial growth factor and increased collagen type I. BV stimulates the proliferation and migration of human epidermal keratinocytes and fibroblasts. In combination with polyvinyl alcohol and chitosan, BV significantly accelerates the wound healing process, increasing the hydroxyproline and glutathione and lowering the IL-6 level in wound tissues. The effect of BV on the wounds has been proved by numerous studies, which revealed that BV in the wound healing process brings about a curative effect and could be applied as a new potential treatment for wound repair. However, therapy with bee venom may induce allergic reactions, so it is necessary to assess the existence of the patient’s hypersensitivity to apitoxin before treatment.
Photodestruction of Diatomic Molecular Ions: Laboratory and Astrophysical Application
Authors: Srećković Vladimir A. , Ignjatović Ljubinko M. , Dimitrijević Milan S.
Published: December 2020

In this work, the processes of photodissociation of some diatomic molecular ions are investigated. The partial photodissociation cross-sections for the individual rovibrational states of the diatomic molecular ions, which involves alkali metals, as well as corresponding data on molecular species and molecular state characterizations, are calculated. Also, the average cross-section and the corresponding spectral absorption rate coefficients for those small molecules are presented in tabulated form as a function of wavelengths and temperatures. The presented results can be of interest for laboratory plasmas as well as for the research of chemistry of different stellar objects with various astrophysical plasmas.
The Anticancer Peptide CIGB-552 Exerts Anti-Inflammatory and Anti-Angiogenic Effects through COMMD1
Authors: Daghero Hellen , Fernández Massó Julio Raúl , Astrada Soledad , Guerra Vallespí Maribel , Bollati-Fogolín Mariela
Published: December 2020

CIGB-552 is a synthetic anti-tumor peptide capable of reducing tumor size and increasing the lifespan of tumor-bearing mice. Part of its anti-cancer effects consists of inducing apoptosis, modulating NF-kB signaling pathway, and the angiogenesis process. Although one of its major mediators, the COMMD1 protein, has been identified, the mechanism by which CIGB-552 exerts such effects remains elusive. In the present study, we show the role of COMMD1 in CIGB-552 mechanism of action by generating the COMMD1 knock-out from the human lung cancer cell line NCI-H460. A microarray was performed to analyze both wild-type and KO cell lines with regard to CIGB-552 treatment. Additionally, different signaling pathways were studied in both cell lines to validate the results. Furthermore, the interaction between CIGB-552 and COMMD1 was analyzed by confocal microscopy. By signaling pathway analysis we found that genes involved in cell proliferation and apoptosis, oncogenic transformation, angiogenesis and inflammatory response are potentially regulated by the treatment with CIGB-552. We then demonstrated that CIGB-552 is capable of modulating NF-kB in both 2D and 3D cell culture models. Finally, we show that the ability of CIGB-552 to negatively modulate NF-kB and HIF-1 pathways is impaired in the COMMD1 knock-out NCI-H460 cell line, confirming that COMMD1 is essential for the peptide mechanism of action.
BODIPY-Based Molecules, a Platform for Photonic and Solar Cells
Authors: Squeo Benedetta Maria , Ganzer Lucia , Virgili Tersilla , Pasini Mariacecilia
Published: December 2020

The 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based molecules have emerged as interesting material for optoelectronic applications. The facile structural modification of BODIPY core provides an opportunity to fine-tune its photophysical and optoelectronic properties thanks to the presence of eight reactive sites which allows for the developing of a large number of functionalized derivatives for various applications. This review will focus on BODIPY application as solid-state active material in solar cells and in photonic devices. It has been divided into two sections dedicated to the two different applications. This review provides a concise and precise description of the experimental results, their interpretation as well as the conclusions that can be drawn. The main current research outcomes are summarized to guide the readers towards the full exploitation of the use of this material in optoelectronic applications.
Editorial to the Special Issue “Gulliver in the Country of Lilliput: An Interplay of Noncovalent Interactions”
Authors: Shenderovich Ilya G.
Published: December 2020

Noncovalent interactions allow our world to exist [...]
EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer’s Disease
Authors: Khavinson Vladimir , Linkova Natalia , Kozhevnikova Ekaterina , Trofimova Svetlana
Published: December 2020

The EDR peptide (Glu-Asp-Arg) has been previously established to possess neuroprotective properties. It activates gene expression and synthesis of proteins, involved in maintaining the neuronal functional activity, and reduces the intensity of their apoptosis in in vitro and in vivo studies. The EDR peptide interferes with the elimination of dendritic spines in neuronal cultures obtained from mice with Alzheimer’s (AD) and Huntington’s diseases. The tripeptide promotes the activation of the antioxidant enzyme synthesis in the culture of cerebellum neurons in rats. The EDR peptide normalizes behavioral responses in animal studies and improves memory issues in elderly patients. The purpose of this review is to analyze the molecular and genetics aspects of the EDR peptide effect on gene expression and synthesis of proteins involved in the pathogenesis of AD. The EDR peptide is assumed to enter cells and bind to histone proteins and/or ribonucleic acids. Thus, the EDR peptide can change the activity of the MAPK/ERK signaling pathway, the synthesis of proapoptotic proteins (caspase-3, p53), proteins of the antioxidant system (SOD2, GPX1), transcription factors PPARA, PPARG, serotonin, calmodulin. The abovementioned signaling pathway and proteins are the components of pathogenesis in AD. The EDR peptide can be AD.
The Effects of a Trace Amount of Manganese and the Homogenization on the Recrystallization of Al–7Mg–0.15Ti Alloys
Authors: Chiu Yang-Chun , Pan Tse-An , Chen Guan-Ming , Jiang Xin-Cheng , Bor Hui-Yun , Tzeng Yu-Chih , Lee Sheng-Long
Published: December 2020

The aim of this study is to explore the effects of Manganese addition and homogenization treatment on the microstructures and mechanical properties of the Al–7Mg–0.15Ti (B535.0) alloy. The optical microscopy, electrical conductivity measurements, transmission electron microscopy, scanning electron microscopy (SEM + EBSD), as well as Rockwell hardness and tensile tests, were exploited for this purpose. The main objectives are to refine the grain size, inhibit grain growth in the annealed state, and enhance the mechanical strength of the alloy. The results show that the addition of manganese to the Al–7Mg–0.15Ti alloys refined the as-cast and recrystallized grains of the alloys. During the homogenization process, Al4Mn high-temperature stable dispersoids were precipitated in the aluminum matrix. After annealing, the Al4Mn particles blocked the movement of grain boundaries during the growth of the recrystallized grains and inhibited grain growth. Consequently, the annealed alloys showed grain refinement and dispersion strengthening. The Al4Mn dispersoids of the alloys with manganese added were smaller and denser after a two-stage homogenization process compared to those that underwent a one-stage homogenization process. By contrast, for the alloys without the addition of manganese, the recrystallized grains showed normal growth after annealing, and different homogenization processes had no significantly different effects.
Incidence of Fusarium Mycotoxins in Wheat and Maize from Albania
Authors: Topi Dritan , Babič Janja , Pavšič-Vrtač Katarina , Tavčar-Kalcher Gabrijela , Jakovac-Strajn Breda
Published: December 2020

In this study, ten Fusarium toxins were analysed in wheat and maize commodities from Albania. In total, 71 samples of wheat and 45 samples of maize were collected from different producing regions. The analytical procedure consisted of a simple one-step sample extraction followed by the determination of toxins using liquid chromatography coupled with tandem mass spectrometry. Fusarium toxins were found in 23% of the analysed wheat samples and in 78% of maize samples. In maize samples, most often fumonisins B1 (FB1) and B2 (FB2) were found. They were present in 76% of samples. They were detected in all positive samples except in one with concentrations ranging from 59.9 to 16,970 μg/kg. The sum of FB1 and FB2 exceeded the EU maximum permitted level (4000 μg/kg) in 31% of maize samples. In wheat samples, the only detected Fusarium mycotoxin was deoxynivalenol (DON), present in 23% of samples. In one sample with the concentration of 1916 μg/kg, the EU maximum permitted level (1250 μg/kg) was exceeded. This is the first report on the presence of Fusarium toxins in wheat and maize grains cultivated in Albania.
Depth-Sensing Hardness Measurements to Probe Hardening Behaviour and Dynamic Strain Ageing Effects of Iron during Tensile Pre-Deformation
Authors: Veleva Lyubomira , Hähner Peter , Dubinko Andrii , Khvan Tymofii , Terentyev Dmitry , Ruiz-Moreno Ana
Published: December 2020

This work reports results from quasi-static nanoindentation measurements of iron, in the un-strained state and subjected to 15% tensile pre-straining at room temperature, 125 °C and 300 °C, in order to extract room temperature hardness and elastic modulus as a function of indentation depth. The material is found to exhibit increased disposition for pile-up formation due to the pre-straining, affecting the evaluation of the mechanical properties of the material. Nanoindentation data obtained with and without pre-straining are compared with bulk tensile properties derived from the tensile pre-straining tests at various temperatures. A significant mismatch between the hardness of the material and the tensile test results is observed and attributed to increased pile-up behaviour of the material after pre-straining, as evidenced by atomic force microscopy. The observations can be quantitatively reconciled by an elastic modulus correction applied to the nanoindentation data, and the remaining discrepancies explained by taking into account that strain hardening behaviour and nano-hardness results are closely affected by dynamic strain ageing caused by carbon interstitial impurities, which is clearly manifested at the intermediate temperature of 125 °C.
Helium Isotopes Quantum Sieving through Graphtriyne Membranes
Authors: Hernández Marta I. , Bartolomei Massimiliano , Campos-Martínez José
Published: December 2020

We report accurate quantum calculations of the sieving of Helium atoms by two-dimensional (2D) graphtriyne layers with a new interaction potential. Thermal rate constants and permeances in an ample temperature range are computed and compared for both Helium isotopes. With a pore larger than graphdiyne, the most common member of the γ-graphyne family, it could be expected that the appearance of quantum effects were more limited. We find, however, a strong quantum behavior that can be attributed to the presence of selective adsorption resonances, with a pronounced effect in the low temperature regime. This effect leads to the appearance of some selectivity at very low temperatures and the possibility for the heavier isotope to cross the membrane more efficiently than the lighter, contrarily to what happened with graphdiyne membranes, where the sieving at low energy is predominantly ruled by quantum tunneling. The use of more approximate methods could be not advisable in these situations and prototypical transition state theory treatments might lead to large errors.
The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials
Authors: Abboud Myriam , Rizk Rana , AlAnouti Fatme , Papandreou Dimitrios , Haidar Suzan , Mahboub Nadine
Published: December 2020

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6–12 weeks, and included 50–105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus, Bifidobacterium, and Streptococcus. Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation.
Diet Quality Is Associated with Serum Antioxidant Capacity in Women with Breast Cancer: A Cross Sectional Study
Authors: Reitz Luiza K. , Baptista Sheyla de L. , Santos Elaine da S. , Hinnig Patrícia F. , Rockenbach Gabriele , Vieira Francilene G. K. , de Assis Maria A. A. , da Silva Edson L. , Boaventura Brunna C. B. , Pietro Patrícia F. Di
Published: December 2020

Oxidative stress produced by adjuvant treatments is associated with cell injury; however, a healthy diet can help mitigate it. The aim of this study is to investigate the association between diet quality and oxidative stress parameters in women subjected to adjuvant treatment for breast cancer. The sample comprised 70 women. Oxidative stress biomarkers and diet quality parameters based on the Brazilian Healthy Eating Index—Revised (BHEI-R)—were evaluated at baseline (p0) and after adjuvant treatment (p1). Ferric reducing antioxidant potential (FRAP) was associated with diet quality at p0. BHEI-R scores were not different between p0 and p1; however, scores from total vegetables, total fruits, milk and dairy products, and meat, eggs and legumes were lower during treatment. On the other hand, lower sodium and saturated fat intake observed at p1 counterbalanced the BHEI-R score. Oxidative stress parameters have increased at p1, but they were not associated with diet quality; thus, changes in component intake were not enough to promote changes in oxidative stress during treatment. It appears that diet can enhance patients’ antioxidant defense before treatment, which could lead to better outcomes in the long term. Further investigations may help to clarify the association between diet and oxidative stress in women with breast cancer.
Healthy Obese Subjects Differ in Chronotype, Sleep Habits, and Adipose Tissue Fatty Acid Composition from Their Non-Healthy Counterparts
Authors: Torres-Castillo Nathaly , Martinez-Lopez Erika , Vizmanos-Lamotte Barbara , Garaulet Marta
Published: December 2020

Obesity is not the same in all individuals and two different phenotypes have been described: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The aim of this study was to identify factors that explain metabolic health status in a rigorously matched Spanish population. Subcutaneous and visceral fat, adipocyte size and fatty acid composition, cardiometabolic markers in serum, and lifestyle habits were assessed. Higher physical activity in the mornings (Odds Ratio (95% Confidence Interval) (OR (95% CI) = 1.54 (1.09–2.18), p = 0.01)), earlier bedtimes (8:30–10:30 pm) (OR = 2.11 (1.02–4.36), p = 0.04), a complete breakfast (OR = 1.59 (1.07–2.36), p = 0.02), and a greater number of meals per day (4.10 ± 0.05 vs. 3.93 ± 0.05, p < 0.01), were associated with the MHO phenotype. Concentrations of 20:5 n-3 eicosapentaenoic acid (0.26 ± 0.46 vs. 0.10% ± 0.11%, p = 0.04) and 18:3 n-6 gamma-linolenic acid (0.37 ± 0.24 vs. 0.23% ± 0.22%, p = 0.04) in subcutaneous adipocytes were higher and omental adipocyte size (187 094 ± 224 059 µm3 vs. 490 953 ± 229 049 µm3, p = 0.02) was lower in MHO subjects than in those with MUO. Visceral fat area differed between MHO and MUO subjects (135 ± 60 cm2 vs. 178 ± 85 cm2, p = 0.04, respectively). The study highlights specific lifestyle habits that could form part of obesity therapies, not only involving healthier eating habits but also earlier sleeping and exercise patterns.
Parents’ Perception of Food Insecurity and of Its Effects on Their Children in Italy Six Months after the COVID-19 Pandemic Outbreak
Authors: Dondi Arianna , Candela Egidio , Morigi Francesca , Lenzi Jacopo , Pierantoni Luca , Lanari Marcello
Published: December 2020

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic and subsequent containment measures are causing an increase in food insecurity (FI) worldwide, with direct consequences on children’s nutrition. We aimed to investigate the effects of the lockdown imposed in Italy on FI and changes in eating habits and body weight in the pediatric population 6 months after the beginning of the pandemic through a cross-sectional online survey proposed to parents of children <18 and living in Italy. Among 5811 respondents, most of whom were Italian, living in Northern Italy, and with a wealthy household economy, 8.3% reported that their families were at risk of FI before the appearance of SARS-CoV-2 and, alarmingly, this percentage increased to 16.2% after the pandemic began, with households from Southern Italy being more at risk. Moreover, 27.3% of the parents reported that their children were eating more; an increase in “junk food” consumption was also found; 31.8% of the respondents declared an increase in children’s weight; weight loss prevailed among adolescents. Since the SARS-CoV-2 pandemic is again requiring restrictions, our findings might serve as a warning to politicians to promote healthy lifestyles and provide assistance to the groups in need.
Malnutrition in Eosinophilic Gastrointestinal Disorders
Authors: Votto Martina , De Filippo Maria , Olivero Francesca , Raffaele Alessandro , Cereda Emanuele , De Amici Mara , Testa Giorgia , Marseglia Gian Luigi , Licari Amelia
Published: December 2020

Primary eosinophilic gastrointestinal disorders (EGIDs) are emerging chronic/remittent inflammatory diseases of unknown etiology, which may involve any part of the gastrointestinal (GI) tract, in the absence of secondary causes of GI eosinophilia. Eosinophilic esophagitis is the prototype of eosinophilic gastrointestinal disorders and is clinically characterized by symptoms related to esophageal inflammation and dysfunction. A few studies have assessed the nutritional status of patients with eosinophilic gastrointestinal disorders, showing conflicting results. This review summarizes the current evidence on the nutritional status of patients with EGIDs, focusing on the pediatric point of view and also speculating potential etiological mechanisms.
Comparison of α-Tocopherol, α-Tocopherol Acetate, and α-Tocopheryl Polyethylene Glycol Succinate 1000 Absorption by Caco-2 TC7 Intestinal Cells
Authors: Cuerq Charlotte , Bordat Claire , Halimi Charlotte , Blond Emilie , Nowicki Marion , Peretti Noël , Reboul Emmanuelle
Published: December 2020

(1) Background: vitamin E is often supplemented in the form of tocopherol acetate, but it has poor bioavailability and can fail to correct blood tocopherol concentrations in some patients with severe cholestasis. In this context, α-tocopheryl polyethylene glycol succinate 1000 (TPGS) has been of value, but very little is known about the mechanisms of its absorption. The aim of our work was to evaluate the mechanisms of absorption/secretion of TPGS compared to tocopherol acetate (TAC) and α-tocopherol by human enterocyte-like Caco-2 TC7 cells. (2) Methods: two weeks post-confluence Caco-2 cells were incubated with tocopherol- or TAC- or TPGS-rich mixed micelles up to 24 h and, following lipid extraction, TAC and tocopherol amounts were measured by high performance liquid chromatography (HPLC) in apical, cellular, and basolateral compartments. (3) Results: at equivalent concentrations of tocopherol in the apical side, the amounts of tocopherol secreted at the basolateral pole of Caco-2 cells are (i) significantly greater when the tocopherol is in the free form in the micelles; (ii) intermediate when it is in the TAC form in the micelles (p < 0.001); and (iii) significantly lower with the TPGS form (p < 0.0001). Interestingly, our results show, for the first time, that Caco-2 cells secrete one or more esterified forms of the vitamin contained in TPGS at the basolateral side.
Quality of Life in Women Diagnosed with Breast Cancer after a 12-Month Treatment of Lifestyle Modifications
Authors: Montagnese Concetta , Porciello Giuseppe , Vitale Sara , Palumbo Elvira , Crispo Anna , Grimaldi Maria , Calabrese Ilaria , Pica Rosa , Prete Melania , Falzone Luca , Libra Massimo , Cubisino Serena , Poletto Luigina , Martinuzzo Valentina , Coluccia Sergio , Esindi Nadia , Nocerino Flavia , Minopoli Anita , Grilli Bruna , Fiorillo Pasqualina C. , Cuomo Marco , Cavalcanti Ernesta , Thomas Guglielmo , Cianniello Daniela , Pinto Monica , De Laurentiis Michelino , Pacilio Carmen , Rinaldo Massimo , D'Aiuto Massimiliano , Serraino Diego , Massarut Samuele , Caggiari Laura , Evangelista Chiara , Steffan Agostino , Catalano Francesca , Banna Giuseppe L. , Scandurra Giuseppa , Ferraù Francesco , Rossello Rosalba , Antonelli Giovanna , Guerra Gennaro , Farina Amalia , Messina Francesco , Riccardi Gabriele , Gatti Davide , Jenkins David J. A. , Celentano Egidio , Botti Gerardo , Augustin Livia S. A.
Published: December 2020

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.
ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
Authors: Hirayama Tatsuro , Miyazaki Taiga , Sumiyoshi Makoto , Ashizawa Nobuyuki , Takazono Takahiro , Yamamoto Kazuko , Imamura Yoshifumi , Izumikawa Koichi , Yanagihara Katsunori , Kohno Shigeru , Mukae Hiroshi
Published: December 2020

Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of ERG3 in intestinal infections is unknown. Here, we infected mice with the C. albicans strains CAE3DU3 and CAF2-1, containing mutant and wild-type ERG3, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (p < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the erg3/erg3 mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type ERG3. These results establish that the ergosterol biosynthetic pathway may be associated with C. albicans gut colonization and subsequent dissemination.
Inactivation of Prions by Low-Temperature Sterilization Technology Using Vaporized Gas Derived from a Hydrogen Peroxide–Peracetic Acid Mixture
Authors: Sakudo Akikazu , Anraku Daiki , Itarashiki Tomomasa
Published: December 2020

Prion diseases are proteopathies that cause neurodegenerative disorders in humans and animals. Prion is highly resistant to both chemical and physical inactivation. Here, vaporized gas derived from a hydrogen peroxide–peracetic acid mixture (VHPPA) was evaluated for its ability to inactivate prion using a STERIACE 100 instrument (Saraya Co., Ltd.). Brain homogenates of scrapie (Chandler strain) prion-infected mice were placed on a cover glass, air-dried, sealed in a Tyvek package, and subjected to VHPPA treatment at 50–55 °C using 8% hydrogen peroxide and <10% peracetic acid for 47 min (standard mode, SD) or 30 min (quick mode, QC). Untreated control samples were prepared in the same way but without VHPPA. The resulting samples were treated with proteinase K (PK) to separate PK-resistant prion protein (PrPres), as a marker of the abnormal isoform (PrPSc). Immunoblotting showed that PrPres was reduced by both SD and QC VHPPA treatments. PrPres bands were detected after protein misfolding cyclic amplification of control but not VHPPA-treated samples. In mice injected with prion samples, VHPPA treatment of prion significantly prolonged survival relative to untreated samples, suggesting that it decreases prion infectivity. Taken together, the results show that VHPPA inactivates prions and might be applied to the sterilization of contaminated heat-sensitive medical devices.
Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin
Authors: Tsukigawa Kenji , Imoto Shuhei , Yamasaki Keishi , Nishi Koji , Tsutsumi Toshihiko , Yokoyama Shoko , Ishima Yu , Otagiri Masaki
Published: December 2020

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.
Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis
Authors: Cho HaEun , Shukla Surabhi
Published: December 2020

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that leads to a loss of muscle control due to nerve cells being affected in the brain and spinal cord. Some of the common clinical presentations of ALS include weakness of muscles, changes in behavior, dysfunction in speech, and cognitive difficulties. The cause of ALS is uncertain, but through several studies, it is known that mutations in SOD1 or C9orf72 genes could play a role as a factor of ALS. In addition, studies indicate that an excessive amount of free radicals, the reactive oxygen species (ROS), leads to neuronal damage by the peroxidation of unsaturated fatty acids in the neuronal cells. Edaravone, the newly approved antioxidant drug for ALS, halts the progression of ALS in the early stages through its cytoprotective effect and protects the nerves by reducing ROS. In this review, different aspects of ALS will be discussed, including its pathology, genetic aspect, and diagnosis. This review also focuses on edaravone as a treatment option for ALS, its mechanism of action, and its pharmacological properties. Clinical trials and adverse effects of edaravone and care for ALS patient are also discussed.
The Effect of Novel Oleanolic Acid Oximes Conjugated with Indomethacin on the Nrf2-ARE And NF-κB Signaling Pathways in Normal Hepatocytes and Human Hepatocellular Cancer Cells
Authors: Narożna Maria , Krajka-Kuźniak Violetta , Bednarczyk-Cwynar Barbara , Kleszcz Robert , Baer-Dubowska Wanda
Published: December 2020

Nrf2 and NF-κB play a key role in inflammation-driven cancers. Conjugation of anti-inflammatory drugs with oleanolic acid oxime (OAO) may enhance their therapeutic potential as a result of downregulation of these pathways. Novel OAO derivatives conjugated with indomethacin (IND) were synthesized, and their effect on the activation and expression of Nrf2 and NF-κB in HepG2 hepatoma cells and THLE-2 immortalized normal hepatocytes was evaluated in relation to cell cycle arrest and apoptosis. Treatment with OAO–IND conjugates reduced the activation of Nrf2 and NF-κB and the expression of their active forms in HepG2 cells, while in normal hepatocytes, the activation of Nrf2 was increased and NF-κB diminished. Compounds 3d, 3-indomethacinoxyiminoolean-12-en-28-oic acid morpholide, and 3c, 3-indomethacinoxyiminoolean-12-en-28-oic acid benzyl ester, were the most efficient. In THLE-2 cells, as opposed to HepG2 cells, the expressions of SOD-1 and NQO1 were significantly enhanced after treatment with these compounds. The COX-2 expression was diminished in both cell lines. OAO–IND derivatives affected the cell cycle arrest at G2/M, leading to increased apoptosis and increased number of resting HepG2 cells. Therefore, the conjugation of IND with OAO derivatives may preserve cancer cells against chemoresistance through the inhibition of the Nrf2-ARE pathway and NF-κB and, at the same time, exert a chemopreventive effect in normal hepatocytes.
Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging
Authors: Nwagwu Chibueze D. , Immidisetti Amanda V. , Bukanowska Gabriela , Vogelbaum Michael A. , Carbonell Anne-Marie
Published: December 2020

Introduction: OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for the intratumoral, convection-enhanced delivery (CED) of OS2966. Gadolinium contrast will be added to OS2966 before each infusion, enabling the real-time visualization of therapeutic distribution via MRI. Subsequently, patients will undergo their clinically indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: (1) the latest CED technology, (2) 2-part design including neoadjuvant intratumoral administration, (3) a first-in-class investigational therapeutic, and (4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active.