bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Investigation of Azobenzene-Based Photochromic Dyes for Dye-Sensitized Solar Cells
Authors: Rashid Md Al Mamunur , Hayati Dini , Kwak Kyungwon , Hong Jongin
Published: May 2020

Two donor-π-spacer-acceptor (D-π-A) organic dyes were designed as photochromic dyes with the same π-spacer and acceptor but different donors, based on their electron-donating strength. Various structural, electronic, and optical properties, chemical reactivity parameters, and certain crucial factors that affect short-circuit current density (Jsc) and open circuit voltage (Voc) were investigated computationally using density functional theory and time-dependent density functional theory. The trans-cis isomerization of these azobenzene-based dyes and its effect on their properties was studied in detail. Furthermore, the dye-(TiO2)9 anatase nanoparticle system was simulated to understand the electronic structure of the interface. Based on the results, we justified how the trans-cis isomerization and different donor groups influence the physical properties as well as the photovoltaic performance of the resultant dye-sensitized solar cells (DSSCs). These theoretical calculations can be used for the rapid screening of promising dyes and their optimization for photochromic DSSCs.
Influence of the Surface Functionalization on the Fate and Performance of Mesoporous Silica Nanoparticles
Authors: Gisbert-Garzarán Miguel , Vallet-Regí María
Published: May 2020

Mesoporous silica nanoparticles have been broadly applied as drug delivery systems owing to their exquisite features, such as excellent textural properties or biocompatibility. However, there are various biological barriers that prevent their proper translation into the clinic, including: (1) lack of selectivity toward tumor tissues, (2) lack of selectivity for tumoral cells and (3) endosomal sequestration of the particles upon internalization. In addition, their open porous structure may lead to premature drug release, consequently affecting healthy tissues and decreasing the efficacy of the treatment. First, this review will provide a comprehensive and systematic overview of the different approximations that have been implemented into mesoporous silica nanoparticles to overcome each of such biological barriers. Afterward, the potential premature and non-specific drug release from these mesoporous nanocarriers will be addressed by introducing the concept of stimuli-responsive gatekeepers, which endow the particles with on-demand and localized drug delivery.
Nano Serpentine Powders as Lubricant Additive: Tribological Behaviors and Self-Repairing Performance on Worn Surface
Authors: Wang Binbin , Zhong Zhaodong , Qiu Han , Chen Dexin , Li Wei , Li Shuangjian , Tu Xiaohui
Published: May 2020

Natural serpentine powders are applicable as additives for various lubricating oils. However, no uniform theories explain their tribological performance, lubrication, and wear mechanism, especially their self-repairing mechanism. Herein, the influence of different nano serpentine powders (NSPs) contents in liquid paraffin on the friction and wear characteristics of steel balls and the self-repairing process of NSPs on the worn surface were studied. Results show that the optimal amount of NSPs was 0.5 wt %. Relative to those of the base oil, the friction coefficients and wear spot diameters were reduced by 22.8% and 34.2%, respectively. Moreover, the long-term tribological test shows that the wear scar diameter decreased slightly after 3 h, reaching the state of dynamic balance between wear and repair. The outstanding tribological performance should be attributed to the formed bilayer tribofilm, the first layer of which contains nanoparticles surrounded by lubricants and the second layer of which contains nanoparticles compacted onto the surface of the steel ball.
Electronic and Thermal Properties of Graphene
Authors: Rhee Kyong Yop
Published: May 2020

Recently, the development of nanotechnology has bloomed in numerous industries [...]
Gold Nanocylinders on Gold Film as a Multi-spectral SERS Substrate
Authors: Safar Wafa , Lequeux Médéric , Solard Jeanne , Fischer Alexis P.A. , Felidj Nordin , Gucciardi Pietro Giuseppe , Edely Mathieu , de la Chapelle Marc Lamy
Published: May 2020

The surface enhanced Raman scattering (SERS) efficiency of gold nanocylinders deposited on gold thin film is studied. Exploiting the specific plasmonic properties of such substrates, we determine the influence of the nanocylinder diameter and the film thickness on the SERS signal at three different excitation wavelengths (532, 638 and 785 nm). We demonstrate that the highest signal is reached for the highest diameter of 250 nm due to coupling between the nanocylinders and for the lowest thickness (20 nm) as the excited plasmon is created at the interface between the gold and glass substrate. Moreover, even if we show that the highest SERS efficiency is obtained for an excitation wavelength of 638 nm, a large SERS signal can be obtained at all excitation wavelengths and on a wide spectral range. We demonstrate that it can be related with the nature of the plasmon (propagative plasmon excited through the nanocylinder grating) and with its angular dependence (tuning of the plasmon position with the excitation angle). Such an effect allows the excitation of plasmon on nearly the whole visible range, and paves the way to multispectral SERS substrates.
Fluorescent Carbon Quantum Dots—Synthesis, Functionalization and Sensing Application in Food Analysis
Authors: Pan Mingfei , Xie Xiaoqian , Liu Kaixin , Yang Jingying , Hong Liping , Wang Shuo
Published: May 2020

Carbon quantum dots (CQDs) with stable physicochemical properties are one of the emerging carbon nanomaterials that have been studied in recent years. In addition to the excellent optical properties such as photoluminescence, photobleaching resistance and light stability, this material also has favorable advantages of good biocompatibility and easy functionalization, which make it an ideal raw material for constructing sensing equipment. In addition, CQDs can combined with other kinds of materials to form the nanostructured composites with unique properties, which provides new insights and ideas for the research of many fields. In the field of food analysis, emerging CQDs have been deeply studied in food composition analysis, detection and monitoring trace harmful substances and made remarkable research progress. This article introduces and compares the various methods for CQDs preparation and reviews its related sensing applications as a new material in food components analysis and food safety inspection in recent years. It is expected to provide a significant guidance for the further study of CQDs in the field of food analysis and detection.
Intratumoral Heterogeneity of Expression of 16 miRNA in Luminal Cancer of the Mammary Gland
Authors: Veryaskina Yuliya A. , Titov Sergei E. , Kometova Vlada V. , Rodionov Valerii V. , Zhimulev Igor F.
Published: May 2020

The purpose of this work is to determine the intratumoral distribution of miRNA expression profiles in luminal breast cancer (BC). The study included 33 certain BC cases of the luminal A or luminal B (Her2-) subtypes. The relative expression levels of miRNA-20a; -21; -125b; -126; -200b; -181a; -205; -221; -222; -451a; -99a; -145; -200a; -214; -30a; -191; and small nuclear RNAs U6, U54, and U58 were measured by RT-qPCR in four intratumor areas in each of 33 luminal BC specimens and in surrounding normal mammary gland tissues. Comparative analysis of miRNA expression levels between normal mammary gland tissue and different intratumor areas revealed that only four miRNAs (miRNA-21, -200b, -200a, -191) appear as consistently differentiating markers. A comparative analysis of miRNA expression levels between normal mammary gland tissue and the tumor border revealed statistically significant differences for ten miRNAs; 10 miRNAs show differential expression between normal mammary gland tissue and central tumor specimens; 9 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 1; 13 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 2. After comparing the tumor periphery 1 and tumor center, we found statistically significant differences in expression between five miRNAs and after comparing the tumor periphery 2 and tumor center, differences were observed for 12 miRNAs. MiRNA expression levels are subject to considerable variation, depending on the intratumor area. This may explain the inconsistency in miRNA expression estimates in BC coming from different laboratories.
Impact of Epigenetics on Complications of Fanconi Anemia: The Role of Vitamin D-Modulated Immunity
Authors: Velleuer Eunike , Carlberg Carsten
Published: May 2020

Fanconi anemia (FA) is a rare disorder with the clinical characteristics of (i) specific malformations at birth, (ii) progressive bone marrow failure already during early childhood and (iii) dramatically increased risk of developing cancer in early age, such as acute myeloid leukemia and squamous cell carcinoma. Patients with FA show DNA fragility due to a defect in the DNA repair machinery based on predominately recessive mutations in 23 genes. Interestingly, patients originating from the same family and sharing an identical mutation, frequently show significant differences in their clinical presentation. This implies that epigenetics plays an important role in the manifestation of the disease. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 controls cellular growth, differentiation and apoptosis via the modulation of the immune system. The nuclear hormone activates the transcription factor vitamin D receptor that affects, via fine-tuning of the epigenome, the transcription of >1000 human genes. In this review, we discuss that changes in the epigenome, in particular in immune cells, may be central for the clinical manifestation of FA. These epigenetic changes can be modulated by vitamin D suggesting that the individual FA patient’s vitamin D status and responsiveness are of critical importance for disease progression.
Obesity and Age-Related Changes in the Brain of the Zucker Lepr fa/fa Rats
Authors: Tomassoni Daniele , Martinelli Ilenia , Moruzzi Michele , Micioni Di Bonaventura Maria Vittoria , Cifani Carlo , Amenta Francesco , Tayebati Seyed Khosrow
Published: May 2020

Metabolic syndrome (MetS) is an association between obesity, dyslipidemia, hyperglycemia, hypertension, and insulin resistance. A relationship between MetS and vascular dementia was hypothesized. The purpose of this work is to investigate brain microanatomy alterations in obese Zucker rats (OZRs), as a model of MetS, compared to their counterparts lean Zucker rats (LZRs). 12-, 16-, and 20-weeks-old male OZRs and LZRs were studied. General physiological parameters and blood values were measured. Immunochemical and immunohistochemical techniques were applied to analyze the brain alterations. The morphology of nerve cells and axons, astrocytes and microglia were investigated. The blood–brain barrier (BBB) changes occurring in OZRs were assessed as well using aquaporin-4 (AQP4) and glucose transporter protein-1 (GLUT1) as markers. Body weight gain, hypertension, hyperglycemia, and hyperlipidemia were found in OZRs compared to LZRs. In the frontal cortex and hippocampus, a decrease of neurons was noticeable in the older obese rats in comparison to their age-matched lean counterparts. In OZRs, a reduction of neurofilament immunoreaction and gliosis was observed. The BBB of older OZRs revealed an increased expression of AQP4 likely related to the development of edema. A down-regulation of GLUT1 was found in OZRs of 12 weeks of age, whereas it increased in older OZRs. The behavioral analysis revealed cognitive alterations in 20-week-old OZRs. Based on these results, the OZRs may be useful for understanding the mechanisms through which obesity and related metabolic alterations induce neurodegeneration.
Biomarkers and Hematological Indices in the Diagnosis of Iron Deficiency in Children with Inflammatory Bowel Disease
Authors: Krawiec Paulina , Pac-Kożuchowska Elżbieta
Published: May 2020

Inflammation may affect many routinely available parameters of iron homeostasis. Thus, the recognition of iron deficiency in inflammatory bowel disease (IBD) remains a diagnostic challenge in a clinical routine. The aim of the study was to detect the most efficient marker of iron deficiency in IBD children. In a group of 75 IBD children, we evaluated the sensitivity, specificity, accuracy, and positive and negative predictive values of erythrocytes’ indices, including MCV, MCH, MCHC and RDW, and biochemical markers, including iron, transferrin, sTfR and sTfR/log ferritin, for identifying iron deficiency. Receiver operating characteristic (ROC) analysis was used to compare the ability of these parameters to detect iron deficiency. The best predictors of iron deficiency were sTfR/log ferritin, with accuracy 0.86, sensitivity 0.98, specificity 0.63, positive predictive value 0.83 and negative predictive value 0.94, and sTfR, with accuracy 0.77, sensitivity 0.82, specificity 0.67, positive predictive value 0.82 and negative predictive value 0.67. Moreover, sTfR/log ferritin exhibited the largest area under ROC (0.922), followed by sTfR (0.755) and MCH (0.720). The sTfR/log ferritin index appears to be the most efficient marker of iron depletion in pediatric IBD, and it may give an added value in the management of IBD patients.
25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2
Authors: D’Avolio Antonio , Avataneo Valeria , Manca Alessandra , Cusato Jessica , De Nicolò Amedeo , Lucchini Renzo , Keller Franco , Cantù Marco
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.
Momentary Physical Activity Co-Occurs with Healthy and Unhealthy Dietary Intake in African American College Freshmen
Authors: Maher Jaclyn P. , Harduk Meghan , Hevel Derek J. , Adams William M. , McGuirt Jared T.
Published: May 2020

Background: Research investigating interrelations between physical activity and dietary intake has primarily used retrospective, summary-based measures of behavior subject to increased recall bias. This study used ecological momentary assessment (EMA) methods with accelerometry to determine within-day, momentary associations between physical activity and dietary intake behaviors in African American college freshmen. Methods: Participants (N = 50) completed a dietary EMA protocol that assessed food/fluids consumed over the past 2 h at five random times per day and wore an activPAL accelerometer for 7 days to measure physical activity. Physical activity was operationalized as step counts in the 2 h prior to the EMA prompt (matching the EMA recall window). Results: On occasions when participants took more steps than was typical for them in the 2 h prior to the EMA prompt, they were more likely to consume sugar-sweetened beverages (OR = 1.37, p < 0.001), water (OR = 1.28, p < 0.001), fruit (OR = 1.44, p < 0.001), vegetables (OR = 1.19, p = 0.02), and fried fast food (OR = 1.21, p = 0.04) over that same time. Conclusion: Momentary physical activity co-occurred with momentary consumption of both healthy and unhealthy dietary intake. These behavioral interrelations suggest potential implications for obesity risk and multiple health behavior change interventions in young adult African Americans.
Sleep Quality in Obesity: Does Adherence to the Mediterranean Diet Matter?
Authors: Muscogiuri Giovanna , Barrea Luigi , Aprano Sara , Framondi Lydia , Di Matteo Rossana , Laudisio Daniela , Pugliese Gabriella , Savastano Silvia , Colao Annamaria
Published: May 2020

Obesity and unhealthy eating habits have been associated with sleep disturbances (SD). The Mediterranean diet (MD) is a healthy nutritional pattern that has been reported to be associated with better health and sleep quality. Thus, the aim of the study was to investigate whether adherence to the MD is associated with sleep quality in a population of middle-aged Italian adults. This cross-sectional study included 172 middle-aged adults (71.5% females; 51.8 ± 15.7 years) that were consecutively enrolled in a campaign to prevent obesity called the OPERA (Obesity, Programs of Nutrition, Education, Research and Assessment of the best treatment) prevention project that was held in Naples on 11–13 October 2019. Anthropometric parameters, adherence to the MD and sleep quality were studied. Overall, 50.6% of the subjects were good sleepers (the Pittsburgh Sleep Quality Index (PSQI) < 5) while 49.4% were poor sleepers (PSQI ≥ 5). Our results demonstrated that good sleepers, when compared to poor sleepers (p < 0.001) had significantly higher adherence to the MD as assessed by PREDIMED (Prevención con Dieta Mediterránea) score, lower BMI (body mass index) and waist circumference (WC). The higher PSQI, the higher the BMI (p < 0.001) and WC values (p < 0.001), thus suggesting that poor sleep was more common in subjects with obesity. In addition, a negative correlation between PSQI and the PREDIMED score (p < 0.001) was found. to the intake of the cluster of foods enclosed in the MD, rather than the intake of the single food, predicted PSQI. By performing a receiver operator characteristic (ROC) curve analysis, we determined a cut-off value at a PREDIMED score < 9 as the threshold for screening poor sleepers. In conclusion, good sleepers had lower BMI and WC and higher adherence to the MD than poor sleepers. PSQI was positively associated to BMI and WC while it was negatively associated to adherence to the MD. The consumption of the MD dietary pattern rather than the intake of a single nutrient has a beneficial effect on sleep quality. Hence, the assessment of sleep should be taken into account in the management of obesity and promoting adherence to the MD could be a tool to improve SD.
Association of Sarcopenic Dysphagia with Underlying Sarcopenia Following Hip Fracture Surgery in Older Women
Authors: Nagano Ayano , Maeda Keisuke , Shimizu Akio , Nagami Shinsuke , Takigawa Naohide , Ueshima Junko , Suenaga Masaki
Published: May 2020

This study aimed to investigate the association between the development of dysphagia in patients with underlying sarcopenia and the prevalence of sarcopenic dysphagia in older patients following surgical treatment for hip fracture. Older female patients with hip fractures (n = 89) were studied. The data of skeletal muscle mass, hand-grip strength, and nutritional status were examined. The development of dysphagia postoperatively was graded using the Food Oral Intake Scale by a certified nurse in dysphagia nursing. The patients’ mean age was 85.9 ± 6.5 years. The prevalence of sarcopenia was 76.4% at baseline. Of the 89 patients, 11 (12.3%) and 12 (13.5%) had dysphagia by day 7 of hospitalization and at discharge, respectively. All patients who developed dysphagia had underlying sarcopenia. Lower skeletal muscle mass index (SMI) (<4.7 kg/m2) and grip strength (<8 kg) at baseline indicated a higher incidence of dysphagia on day 7 (p = 0.003 and Phi = 0.391) and at discharge (p = 0.001 and Phi = 0.448). Dysphagia developed after hip fracture surgery could be sarcopenic dysphagia, and worsening sarcopenia was a risk factor for dysphagia following hip fracture surgery. Clinicians and medical coworkers should become more aware of the risks of sarcopenic dysphagia. Early detection and preventive interventions for dysphagia should be emphasized.
Daily Coffee and Green Tea Consumption Is Inversely Associated with Body Mass Index, Body Fat Percentage, and Cardio-Ankle Vascular Index in Middle-Aged Japanese Women: A Cross-Sectional Study
Authors: Yonekura Yuka , Terauchi Masakazu , Hirose Asuka , Odai Tamami , Kato Kiyoko , Miyasaka Naoyuki
Published: May 2020

This study aimed to investigate the links between coffee (CF)/green tea (GT) consumption and body composition/cardiovascular parameters in middle-aged Japanese women. We conducted a cross-sectional study of 232 Japanese women aged 40–65 years who had been referred to the menopause clinic of Tokyo Medical and Dental University Hospital between November 2007 and August 2017. Body composition, cardiovascular parameters, and CF/GT consumption frequency were evaluated on their initial visits, using a body composition analyzer, vascular screening system, and brief-type self-administered diet history questionnaire, respectively. We investigated the associations between variables using multivariate logistic regression. After adjustment for age, menopausal status, and other factors, daily CF consumption was inversely associated with high body mass index (BMI) (adjusted odds ratio, 0.14; 95% confidence interval, 0.14–0.96) and body fat percentage (BF%) (0.33; 0.14–0.82), and daily GT consumption with high BF% (0.36; 0.14–0.96). Daily CF + GT consumption was also inversely associated with high BMI (0.15; 0.05–0.50) and BF% (0.30; 0.12–0.74). In pre- and perimenopausal women, daily CF + GT consumption was inversely associated with high cardio-ankle vascular index (CAVI) (0.05; 0.003–0.743). In conclusion, daily CF/GT consumption was inversely associated with high BMI, BF%, and CAVI in middle-aged Japanese women.
The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo
Authors: Choi Jin Gyu , Khan Zahra , Hong Seong Min , Kim Young Choong , Oh Myung Sook , Kim Sun Yeou
Published: May 2020

Nerve growth factor (NGF), a typical neurotrophin, has been characterized by the regulation of neuronal cell differentiation and survival involved in learning and memory functions. NGF has a main role in neurite extension and synapse formation by activating the cyclic adenosine monophosphate-response-element-binding protein (CREB) in the hippocampus. The purpose of this study was to determine whether a mixture of Gotu Kola, Cnidium fruit, and Goji berry (KYJ) enhances memory function by inducing NGF-mediated actions both in vitro and in vivo. The KYJ combination increased NGF concentration and neurite length in C6 glioma and N2a neuronal cells, respectively. Additionally, we discovered memory-enhancing effects of KYJ through increased NGF-mediated synapse maturation, CREB phosphorylation, and cell differentiation in the mouse hippocampus. These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities.
Gender Differences in Fat-Rich Meat Choice: Influence of Personality and Attitudes
Authors: Spinelli Sara , Dinnella Caterina , Tesini Federica , Bendini Alessandra , Braghieri Ada , Proserpio Cristina , Torri Luisa , Miele Nicoletta A. , Aprea Eugenio , Mazzaglia Agata , Gallina Toschi Tullia , Monteleone Erminio
Published: May 2020

The innate liking of fats may be due to one or more orosensory, post-ingestive, and metabolic signals; however, individuals differ in their preference for fat in meat. One of the variables that mainly impacts eating behaviors and thus should be carefully analyzed is sex/gender, and while sex (female/male, in a binary approximation) refers only to biological characteristics, gender (woman/man, in a binary approximation) refers to cultural attitudes and behavior. This study aimed at exploring the role of gender, age, taste responsiveness (measured as sensitivity to the bitterness of 6-n-propylthiouracil (PROP)), personality traits, attitudes, and liking of and familiarity with meat on the choice of fat-rich meat products in 1208 women and men aged 18–66. Both a between- and a within-gender approach were adopted. Results showed that gender had a major impact on liking of and familiarity with meat and choice for fat-rich meat compared to age. A lower liking meat in general was found in women, independently of fat content. Women also reported a lower familiarity than men with fatty meat and cold meat and a lower choice of fat-rich meat. Genders differed in the influence of personality and attitudes about fat-rich meat choice. In both genders, the choice of meat higher in fat was associated with liking cold and fatty meat and with age and negatively with liking low-fat meat. Women were in general more interested in health than men, and this may explain the main difference in the choice of fat-rich meat between genders. However, when we look at each gender separately, general health interest was significantly correlated with a lower choice of fat-rich meat only in men. In addition, in men food neophobia was negatively correlated with choice of fat-rich meat. In women, the emotional dimension was found to play an important role, with sensitivity to disgust that was negatively associated with fat-rich meat choice and emotional eating that was positively associated with it. Thanks to the large sample and the gender-sensitive approach adopted, this study showed that different factors affect choice of fat-rich meat by gender, in addition to liking of and familiarity with fat-rich and cold meat and age. This suggests that strategies personalized by gender to reinforce or activate barriers to this type of consumption may be more effective at reducing fat intake, promoting the consumption of meat lower in fat.
Prenatal Nutrition Containing Bisphenol A Affects Placenta Glucose Transfer: Evidence in Rats and Human Trophoblast
Authors: Benincasa Linda , Mandalà Maurizio , Paulesu Luana , Barberio Laura , Ietta Francesca
Published: May 2020

This work aims to clarify the effect of dietary supplementation with Bisphenol A (BPA), a chemical widely present in beverage and food containers, on placental glucose transfer and pregnancy outcome. The study was performed on female Sprague Dawley rats fed with a diet containing BPA (2.5, 25 or 250 μg/Kg/day) for a period of a month (virgin state) plus 20 days during pregnancy. Western blot analysis and immunohistochemistry were performed in placental tissues for glucose type 1 transporter (GLUT1). Furthermore, human trophoblast, HTR8-SV/neo cells, were used to evaluate the effect of BPA on glucose transport and uptake. Studies in rats showed that food supplementation with BPA, produces a higher fetal weight (FW) to placenta weight (PW) ratio at the lowest BPA concentration. Such low concentrations also reduced maternal weight gain in late pregnancy and up-regulated placental expression of GLUT1. Treatment of HTR8-SV/neo with the non-toxic dose of 1 nM BPA confirmed up-regulation of GLUT1 expression and revealed higher activity of the transporter with an increase in glucose uptake and GLUT1 membrane translocation. Overall, these results indicate that prenatal exposure to BPA affects pregnancy and fetal growth producing changes in the placental nutrients-glucose transfer.
Chyme Reinfusion in Intestinal Failure Related to Temporary Double Enterostomies and Enteroatmospheric Fistulas
Authors: Picot Denis , Layec Sabrina , Seynhaeve Eloi , Dussaulx Laurence , Trivin Florence , Carsin-Mahe Marie
Published: May 2020

Some temporary double enterostomies (DES) or entero-atmospheric fistulas (EAF) have high output and are responsible for Type 2 intestinal failure. Intravenous supplementations (IVS) for parenteral nutrition and hydration compensate for intestinal losses. Chyme reinfusion (CR) artificially restores continuity pending surgical closure. CR treats intestinal failure and is recommended by European Society for Clinical Nutrition and Metabolism (ESPEN) and American Society for Parenteral and Enteral Nutrition (ASPEN) when possible. The objective of this study was to show changes in nutritional status, intestinal function, liver tests, IVS needs during CR, and the feasibility of continuing it at home. A retrospective study of 306 admitted patients treated with CR from 2000 to 2018 was conducted. CR was permanent such that a peristaltic pump sucked the upstream chyme and reinfused it immediately in a tube inserted into the downstream intestine. Weight, plasma albumin, daily volumes of intestinal and fecal losses, intestinal nitrogen, and lipid absorption coefficients, plasma citrulline, liver tests, and calculated indices were compared before and during CR in patients who had both measurements. The patients included 185 males and 121 females and were 63 ± 15 years old. There were 37 (12%), 269 (88%) patients with EAF and DES, respectively. The proximal small bowel length from the duodeno-jejunal angle was 108 ± 67 cm (n = 232), and the length of distal small intestine was 117 ± 72 cm (n = 253). The median CR start was 5 d (quartile 25–75%, 2–10) after admission and continued for 64 d (45–95), including 81 patients at home for 47 d (28–74). Oral feeding was exclusive 171(56%), with enteral supplement 122 (42%), or with IVS 23 (7%). Before CR, 211 (69%) patients had IVS for nutrition (77%) or for hydration (23%). IVS were stopped in 188 (89%) 2 d (0–7) after the beginning of CR and continued in 23 (11%) with lower volumes. Nutritional status improved with respect to weight gain (+3.5 ± 8.4%) and albumin (+5.4 ± 5.8 g/L). Intestinal failure was cured in the majority of cases as evidenced by the decrease in intestinal losses by 2096 ± 959 mL/d, the increase in absorption of nitrogen 32 ± 20%, of lipids 43 ± 30%, and the improvement of citrulline 13.1 ± 8.1 µmol/L. The citrulline increase was correlated with the length of the distal intestine. The number of patients with at least one liver test >2N decreased from 84–40%. In cases of Type 2 intestinal failure related to DES or FAE with an accessible and functional distal small bowel segment, CR restored intestinal functions, reduced the need of IVS by 89% and helped improve nutritional status and liver tests. There were no vital complications or infectious diarrhea described to date. CR can become the first-line treatment for intestinal failure related to double enterostomy and high output fistulas.
Distribution and Genetic Characterization of Border Disease Virus Circulating in Sardinian Ovine Flocks
Authors: Piras Ilaria M. , Dei Giudici Silvia , Fadda Manlio , Anfossi Antonio G. , Oggiano Annalisa , Pittau Marco , Chessa Bernardo
Published: May 2020

Border Disease (BD) is a worldwide distributed pathology accountable for significant losses in the sheep and goat farming industry. The etiological agent is a Pestivirus within the family Flaviviridae called border disease virus (BDV). Despite the Sardinian ovine population being by far larger than any other Italian region, the prevalence and distribution of BD on the island are unknown. Here, we aim to determine the distribution of BDV in sheep flocks and to genetically characterize the circulating strains in Sardinia. The geographical distribution, antibody positivity, and viral genome presence have been analysed for 1286 sheep flocks distributed all over the island from bulk tank milk sampled between May 2014 and 2015. Of the flocks tested, 11.28% (95% CI 9.66–13.12) resulted positive for the presence of anti-pestivirus antibodies with an uneven distribution between Sardinian provinces. In addition, using RT-PCR, nine BDV genomes were amplified from milk pellets of the seropositive samples. Phylogenetic analysis revealed that all the viruses amplified clustered in the same group classified as BDV-7. This represents the first study on the distribution of pestivirus infection and genetic characterization of BDV strains circulating in the Sardinian sheep population. Future studies are needed to clarify the origin, the evolution, and the epidemiology of BDV-7 in Sardinia.
Modulation of Type I Interferon System by African Swine Fever Virus
Authors: Razzuoli Elisabetta , Franzoni Giulia , Carta Tania , Zinellu Susanna , Amadori Massimo , Modesto Paola , Oggiano Annalisa
Published: May 2020

African Swine Fever Virus (ASFV) has tropism for macrophages, which seems to play a crucial role in disease pathogenesis and viral dissemination. Previous studies showed that ASFV developed mechanisms to evade type I interferon (IFN) responses. Hence, we analyzed the ability of ASFV strains of diverse virulence to modulate IFN-β and IFN-α responses. Porcine monocyte-derived macrophages un-activated (moMΦ) or activated with IFN-α (moMΦ + FN-α) were infected with virulent (22653/14) or attenuated (NH/P68) ASFV strains, and expressions of IFN-β and of 17 IFN-α subtypes genes were monitored over time. ASFV strains of diverse virulence induced different panels of IFN genes: infection of moMΦ with either strains caused statistically significant up-regulation of IFN-α3, -α7/11, whereas only attenuated NH/P68 determined statistically significant up-regulation of IFN-α10, -α12, -α13, -α15, -α17, and IFN-β. Infection of activated moMΦ with either strains resulted in up-regulation of IFN-β and many IFN-α subtypes, but statistical significance was found only for IFN-α1, -α10, -α15, -α16, -α17 in response to NH/P68-infection only. These data revealed differences in type I IFNs expression patterns, with differences between strains of diverse virulence. In addition, virulent 22653/14 ASFV seems to have developed mechanisms to suppress the induction of several type I IFN genes.
Correlation between Milk Bacteriology, Cytology and Mammary Tissue Histology in Cows: Cure from the Pathogen or Recovery from the Inflammation
Authors: Leitner Gabriel , Blum Shlomo E. , Krifuks Oloeg , Edery Nir , Merin Uzi
Published: May 2020

The aim of the current study was to verify the existence of a significant correlation between bacterial isolation (or not) and mammary gland inflammation, using traditional bacterial culturing and PCR, milk leucocytes distributions, and tissue histology. Twenty-two cows were tested at the level of the individual gland for bacteriological culture and real-time PCR (RT-PCR), milk composition, somatic cells count (SCC), and cell differentiation. Post-slaughter samples of teat-ends and mammary tissues were tested for histology and bacteriology by RT-PCR. The 88 glands were assigned to either outcome: 1. Healthy—no inflammation and no bacterial finding (NBF) (n = 33); 2. Inflammation and NBF (n = 26); 3. Inflammation and intra-mammary infection (n = 22) with different bacteria. Bacteriology of milk samples and that of the RT-PCR showed 91.4% agreement. In the lobule’s tissues of healthy glands, ~50% were milk producers and the other glands had dry areas with increased fat globules with a low number of leukocytes. In contrast, ~75% of the infected glands were identified as inflamed, but with no isolation of bacteria. Infiltration of mononuclear cells and neutrophils into the connective tissue was observed but not in the lobule’s lumen. In summary, the study confirms that not every mastitis/inflammation is also an infection.
Highly Efficient Vertical Transmission for Zika Virus in Aedes aegypti after Long Extrinsic Incubation Time
Authors: Manuel Menchie , Missé Dorothée , Pompon Julien
Published: May 2020

While the Zika virus (ZIKV) 2014–2017 pandemic has subsided, there remains active transmission. Apart from horizontal transmission to humans, the main vector Aedes aegypti can transmit the virus vertically from mother to offspring. Large variation in vertical transmission (VT) efficiency between studies indicates the influence of parameters, which remain to be characterized. To determine the roles of extrinsic incubation time and gonotrophic cycle, we deployed an experimental design that quantifies ZIKV in individual progeny and larvae. We observed an early infection of ovaries that exponentially progressed. We quantified VT rate, filial infection rate, and viral load per infected larvae at 10 days post oral infection (d.p.i.) on the second gonotrophic cycle and at 17 d.p.i. on the second and third gonotrophic cycle. As compared to previous reports that studied pooled samples, we detected a relatively high VT efficiency from 1.79% at 10 d.p.i. and second gonotrophic cycle to 66% at 17 d.p.i. and second gonotrophic cycle. At 17 d.p.i., viral load largely varied and averaged around 800 genomic RNA (gRNA) copies. Longer incubation time and fewer gonotrophic cycles promoted VT. These results shed light on the mechanism of VT, how environmental conditions favor VT, and whether VT can maintain ZIKV circulation.
Therapeutic Targeting of Pancreatic Cancer via EphA2 Dimeric Agonistic Agents
Authors: Salem Ahmed F. , Gambini Luca , Udompholkul Parima , Baggio Carlo , Pellecchia Maurizio
Published: May 2020

Recently, we reported on potent EphA2 targeting compounds and demonstrated that dimeric versions of such agents can exhibit remarkably increased agonistic activity in cellular assays compared to the monomers. Here we further characterize the activity of dimeric compounds at the structural, biochemical, and cellular level. In particular, we propose a structural model for the mechanism of receptor activation by dimeric agents and characterize the effect of most potent compounds in inducing EphA2 activation and degradation in a pancreatic cancer cell line. These cellular studies indicate that the pro-migratory effects induced by the receptor can be reversed in EphA2 knockout cells, by treatment with either a dimeric natural ligand (ephrinA1-Fc), or by our synthetic agonistic dimers. Based on these data we conclude that the proposed agents hold great potential as possible therapeutics in combination with standard of care, where these could help suppressing a major driver for cell migration and tumor metastases. Finally, we also found that, similar to ephrinA1-Fc, dimeric agents cause a sustained internalization of the EphA2 receptor, hence, with proper derivatizations, these could also be used to deliver chemotherapy selectively to pancreatic tumors.
Compression-Induced Phase Transitions of Bicalutamide
Authors: Szafraniec-Szczęsny Joanna , Antosik-Rogóż Agata , Knapik-Kowalczuk Justyna , Kurek Mateusz , Szefer Ewa , Gawlak Karolina , Chmiel Krzysztof , Peralta Sebastian , Niwiński Krzysztof , Pielichowski Krzysztof , Paluch Marian , Jachowicz Renata
Published: May 2020

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.
Vascular Drug Delivery Using Carrier Red Blood Cells: Focus on RBC Surface Loading and Pharmacokinetics
Authors: Glassman Patrick M. , Villa Carlos H. , Ukidve Anvay , Zhao Zongmin , Smith Paige , Mitragotri Samir , Russell Alan J. , Brenner Jacob S. , Muzykantov Vladimir R.
Published: May 2020

Red blood cells (RBC) have great potential as drug delivery systems, capable of producing unprecedented changes in pharmacokinetics, pharmacodynamics, and immunogenicity. Despite this great potential and nearly 50 years of research, it is only recently that RBC-mediated drug delivery has begun to move out of the academic lab and into industrial drug development. RBC loading with drugs can be performed in several ways—either via encapsulation within the RBC or surface coupling, and either ex vivo or in vivo—depending on the intended application. In this review, we briefly summarize currently used technologies for RBC loading/coupling with an eye on how pharmacokinetics is impacted. Additionally, we provide a detailed description of key ADME (absorption, distribution, metabolism, elimination) changes that would be expected for RBC-associated drugs and address unique features of RBC pharmacokinetics. As thorough understanding of pharmacokinetics is critical in successful translation to the clinic, we expect that this review will provide a jumping off point for further investigations into this area.
Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments
Authors: Gangadaran Prakash , Ahn Byeong-Cheol
Published: May 2020

Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.
Advances in Nanoliposomes Production for Ferrous Sulfate Delivery
Authors: Bochicchio Sabrina , Dalmoro Annalisa , Lamberti Gaetano , Barba Anna Angela
Published: May 2020

In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization.
Liposomal and Ethosomal Gels for the Topical Delivery of Anthralin: Preparation, Comparative Evaluation and Clinical Assessment in Psoriatic Patients
Authors: Fathalla Dina , Youssef Eman M. K. , Soliman Ghareb M.
Published: May 2020

To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers were characterized for drug encapsulation efficiency, size, morphology and compatibility between various components. Optimum formulations were dispersed in various gel bases and drug release kinetics were studied. Clinical efficacy and safety of liposomal and ethosomal Pluronic®F-127 gels were evaluated in patients having psoriasis (clinicaltrials.gov identifier is NCT03348462). Safety was assessed by recording various adverse events. Drug encapsulation efficiency ≥97.2% and ≥77% were obtained for liposomes and ethosomes, respectively. Particle sizes of 116 to 199 nm and 146 to 381 nm were observed for liposomes and ethosomes, respectively. Fourier-Transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the absence of interaction between anthralin and various nanocarrier components. Tested gel bases showed excellent ability to sustain drug release. At baseline, the patients had a median Psoriasis Area and Severity Index (PASI) of 3.4 for liposomes and 3.6 for ethosomes without significant difference. After treatment, mean PASI change was −68.66% and −81.84% for liposomes and ethosomes, respectively with a significant difference in favor of ethosomes. No adverse effects were detected in both groups. Anthralin ethosomes could be considered as a potential treatment of psoriasis.
New Insights on the Role of Allyl Isothiocyanate in Controlling the Root Knot Nematode Meloidogyne hapla
Authors: Dahlin Paul , Hallmann Johannes
Published: May 2020

Biofumigation, although a well-known method, is still controversially debated as a management strategy for plant-parasitic nematodes (PPN). Its controlling effect is attributed to the production of isothiocyanates (ITCs) following the action of myrosinase on glucosinolates (GSLs). Different ITCs are formed from different GSLs, depending on the plant species. To better understand the potential of ITCs, eight cultivars from three Brassicaceae species were investigated as biofumigation crops to control the root knot nematode Meloidogyne hapla. Since results were inconsistent, the nematicidal effect of selected ITCs were further evaluated in vitro. Based on its nematicidal potential, allyl ITC (AITC) was specifically investigated under different soil:sand compositions. A significantly lower nematicidal activity was observed in soil compared to sand. AITC was also evaluated as an additive to the biofumigation in a greenhouse trial. Its supplementation to the biofumigation process with Brassica juncea cv. Terrafit controlled M. hapla, while no control was observed using Raphanus sativus cv. Defender. Thus, the success of biofumigation seems to be strongly dependent on the soil characteristics and the ITC produced during the biofumigation process. Therefore, the supplementation of AITC in combination with the right cover crop can improve the biofumigation process to control M. hapla.