bluuebunny/crossref_metadata_2025 huggingface dataset:
Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro
Authors: Cenariu Diana , Fischer-Fodor Eva , Țigu Adrian Bogdan , Bunea Andrea , Virág Piroska , Perde-Schrepler Maria , Toma Vlad-Alexandru , Mocan Andrei , Berindan-Neagoe Ioana , Pintea Adela , Crișan Gianina , Cenariu Mihai , Maniu Alma
Published: January 2021

The concern for implementing bioactive nutraceuticals in antioxidant-related therapies is of great importance for skin homeostasis in benign or malignant diseases. In order to elucidate some novel insights of Lycium barbarum (Goji berry) activity on skin cells, the present study focused on its active compound zeaxanthin. By targeting the stemness markers CD44 and CD105, with deep implications in skin oxidative stress mechanisms, we revealed, for the first time, selectivity in zeaxanthin activity. When applied in vitro on BJ human fibroblast cell line versus the A375 malignant melanoma cells, despite the moderate cytotoxicity, the zeaxanthin-rich extracts 1 and 2 were able to downregulate significantly the CD44 and CD105 membrane expression and extracellular secretion in A375, and to upregulate them in BJ cells. At mechanistic level, the present study is the first to demonstrate that the zeaxanthin-rich Goji extracts are able to influence selectively the mitogen-activated protein kinases (MAPK): ERK, JNK and p38 in normal BJ versus tumor-derived A375 skin cells. These results point out towards the applications of zeaxanthin from L. barbarum as a cytoprotective agent in normal skin and raises questions about its use as an antitumor prodrug alone or in combination with standard therapy.
Chemosensitization of HT29 and HT29-5FU Cell Lines by a Combination of a Multi-Tyrosine Kinase Inhibitor and 5FU Downregulates ABCC1 and Inhibits PIK3CA in Light of Their Importance in Saudi Colorectal Cancer
Authors: Abdalla Ashraf N. , Malki Waleed H. , Qattan Amal , Shahid Imran , Hossain Mohammad Akbar , Ahmed Muhammad
Published: January 2021

Colorectal cancer (CRC) remains one of the main causes of death worldwide and in Saudi Arabia. The toxicity and the development of resistance against 5 fluorouracil 5FU pose increasing therapeutic difficulties, which necessitates the development of personalized drugs and drug combinations. Objectives: First, to determine the most important kinases and kinase pathways, and the amount of ABC transporters and KRAS in samples taken from Saudi CRC patients. Second, to investigate the chemosensitizing effect of LY294002 and HAA2020 and their combinations with 5FU on HT29, HT29-5FU, HCT116, and HCT116-5FU CRC cells, their effect on the three ABC transporters, cell cycle, and apoptosis, in light of the important kinase pathways resulting from the first part of this study. Methods: The PamChip® peptide micro-array profiling was used to determine the level of kinase and targets in the Saudi CRC samples. Next, RT-PCR, MTT cytotoxicity, Western blotting, perturbation of cell cycle, annexin V, and immunofluorescence assays were used to investigate the effect on CRC, MRC5, and HUVEC cells. Results: The kinase activity profiling highlighted the importance of the PI3K/AKT, MAPK, and the growth factors pathways in the Saudi CRC samples. PIK3CA was the most overexpressed, and it was associated with increased level of mutated KRAS and the three ABC transporters, especially ABCC1 in the Saudi samples. Next, combining HAA2020 with 5FU exhibited the best synergistic and resistance-reversal effect in the four CRC cells, and the highest selectivity indices compared to MRC5 and HUVEC normal cells. Additionally, HAA2020 with 5FU exerted significant inhibition of ABCC1 in the four CRC cells, and inhibition of PIK3CA/AKT/MAPK7/ERK in HT29 and HT29-5FU cells. The combination also inhibited EGFR, increased the preG1/S cell cycle phases, apoptosis, and caspase 8 in HT29 cells, while it increased the G1 phase, p21/p27, and apoptosis in HT29-5FU cells. Conclusion: We have combined the PamChip kinase profiling of Saudi CRC samples with in vitro drug combination studies in four CRC cells, highlighting the importance of targeting PIK3CA and ABCC1 for Saudi CRC patients, especially given that the overexpression of PIK3CA mutations was previously linked with the lack of activity for the anti-EGFRs as first line treatment for CRC patients. The combination of HAA2020 and 5FU has selectively sensitized the four CRC cells to 5FU and could be further studied.
Novel Amides Derivative with Antimicrobial Activity of Piper betle var. nigra Leaves from Indonesia
Authors: Prasetya Fajar , Salam Supriatno , Rahmadani Agung , Haikal Kansy , Febrina Lizma , Anshory Hady , Arifuddin Muhammad , Siregar Vita Olivia , Narsa Angga Cipta , Herman Herman , Ahmad Islamudin , Indriyanti Niken , Ibrahim Arsyik , Rusli Rolan , Rijai Laode , Kuncoro Hadi
Published: January 2021

Piper betle var. nigra is a tropical plant closely related to the common piper. P. betle has also been dubbed a promising source of natural antioxidants in herbal health products, antibacterial, antifungal, antimalarial, cytotoxic activity against the cancer cell lines K562 and HL-60, and antileishmanial. The aim of this study to observation Antimicrobial activity and isolation of chemical compound. The antimicrobial activity of P. betle extract was performed by well diffusion method against two oral pathogenic bacteria (Streptococcus mutans and Streptococcus sanguinis) and opportunistic pathogenic yeast (Candida albicans). The inoculum (bacterial and yeast suspension) was prepared from a 24-h culture on NB for bacterial suspension and on TSB for yeast suspension. Extraction and isolation using various method of chromatography. Isolated compounds were characterized by spectroscopic means. Our study showed antimicrobial activity from crude ethanol extract of leaves P. betle L. var. nigra against two oral pathogenic bacteria and opportunistic pathogenic yeast with concentration 0.5% and 1%. The first report of two new amides derivatives, piperenamide A (1) and piperenamide B (2) in P. betle L. var. nigra.
Melatonin in Wine and Beer: Beneficial Effects
Authors: Marhuenda Javier , Villaño Débora , Arcusa Raúl , Zafrilla Pilar
Published: January 2021

Melatonin is a hormone secreted in the pineal gland with several functions, especially regulation of circadian sleep cycle and the biological processes related to it. This review evaluates the bioavailability of melatonin and resulting metabolites, the presence of melatonin in wine and beer and factors that influence it, and finally the different benefits related to treatment with melatonin. When administered orally, melatonin is mainly absorbed in the rectum and the ileum; it has a half-life of about 0.45–1 h and is extensively inactivated in the liver by phase 2 enzymes. Melatonin (MEL) concentration varies from picograms to ng/mL in fermented beverages such as wine and beer, depending on the fermentation process. These low quantities, within a dietary intake, are enough to reach significant plasma concentrations of melatonin, and are thus able to exert beneficial effects. Melatonin has demonstrated antioxidant, anticarcinogenic, immunomodulatory and neuroprotective actions. These benefits are related to its free radical scavenging properties as well and the direct interaction with melatonin receptors, which are involved in complex intracellular signaling pathways, including inhibition of angiogenesis and cell proliferation, among others. In the present review, the current evidence on the effects of melatonin on different pathophysiological conditions is also discussed.
Profile of Volatile Compounds of On-Farm Fermented and Dried Cocoa Beans Inoculated with Saccharomyces cerevisiae KY794742 and Pichia kudriavzevii KY794725
Authors: Chagas Junior Gilson Celso Albuquerque , Ferreira Nelson Rosa , Andrade Eloisa Helena de Aguiar , Nascimento Lidiane Diniz do , Siqueira Francilia Campos de , Lopes Alessandra Santos
Published: January 2021

This study aimed to identify the volatile compounds in the fermented and dried cocoa beans conducted with three distinct inoculants of yeast species due to their high fermentative capacity: Saccharomyces cerevisiae, Pichia kudriavzevii, the mixture in equal proportions 1:1 of both species, and a control fermentation (with no inoculum application). Three starter cultures of yeasts, previously isolated and identified in cocoa fermentation in the municipality of Tomé-Açu, Pará state, Brazil. The seeds with pulp were removed manually and placed in wooden boxes for the fermentation process that lasted from 6 to 7 days. On the last day of fermentation, the almonds were packaged properly and placed to dry (36 °C), followed by preparation for the analysis of volatile compounds by GC-MS technique. In addition to the control fermentation, a high capacity for the formation of desirable compounds in chocolate by the inoculants with P. kudriavzevii was observed, which was confirmed through multivariate analyses, classifying these almonds with the highest content of aldehydes, esters, ketones and alcohols and low concentration of off-flavours. We conclude that the addition of mixed culture starter can be an excellent alternative for cocoa producers, suggesting obtaining cocoa beans with desirable characteristics for chocolate production, as well as creating a product identity for the producing region.
Inactivation of Material from SARS-CoV-2-Infected Primary Airway Epithelial Cell Cultures
Authors: Barrow Kaitlyn A. , Rich Lucille M. , Vanderwall Elizabeth R. , Reeves Stephen R. , Rathe Jennifer A. , White Maria P. , Debley Jason S.
Published: January 2021

Given that the airway epithelium is the initial site of infection, study of primary human airway epithelial cells (AEC) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be crucial to improved understanding of viral entry factors and innate immune responses to the virus. Centers for Disease Control and Prevention (CDC) guidance recommends work with live SARS-CoV-2 in cell culture be conducted in a Biosafety Level 3 (BSL-3) laboratory. To facilitate downstream assays of materials from experiments there is a need for validated protocols for SARS-CoV-2 inactivation to facilitate safe transfer of material out of a BSL-3 laboratory. We propagated stocks of SARS-CoV-2, then evaluated the effectiveness of heat (65 °C) or ultraviolet (UV) light inactivation. We infected differentiated human primary AECs with SARS-CoV-2, then tested protocols designed to inactivate SARS-CoV-2 in supernatant, protein isolate, RNA, and cells fixed for immunohistochemistry by exposing Vero E6 cells to materials isolated/treated using these protocols. Heating to 65 °C for 10 min or exposing to UV light fully inactivated SARS-CoV-2. Furthermore, we found in SARS-CoV-2-infected primary AEC cultures that treatment of supernatant with UV light, isolation of RNA with Trizol®, isolation of protein using a protocol including sodium dodecyl sulfate (SDS) 0.1% and Triton X100 1%, and fixation of AECs using 10% formalin and Triton X100 1%, each fully inactivated SARS-CoV-2.
In Situ Observation of Electron-Beam-Induced Formation of Nano-Structures in PbTe
Authors: Zelenina Iryna , Veremchuk Igor , Grin Yuri , Simon Paul
Published: January 2021

Nano-scaled thermoelectric materials attract significant interest due to their improved physical properties as compared to bulk materials. Well-shaped nanoparticles such as nano-bars and nano-cubes were observed in the known thermoelectric material PbTe. Their extended two-dimensional nano-layer arrangements form directly in situ through electron-beam treatment in the transmission electron microscope. The experiments show the atomistic depletion mechanism of the initial crystal and the recrystallization of PbTe nanoparticles out of the microparticles due to the local atomic-scale transport via the gas phase beyond a threshold current density of the beam.
Presenting Symptoms and Disease Severity in Multiple Sclerosis Patients
Authors: Ledesma Jason , Puttagunta Padma Priya , Torabi Shayan , Berube Kristen , Tamrazian Eric , Garcia Diamond , Mehta Bijal Kirit
Published: January 2021

Introduction: The study aims to determine an association between presenting symptoms in multiple sclerosis and measures of disease severity, including the expanded disability status score (EDSS) and MRI based lesion volumes. Methods: Data was collected as part of a larger 3 year MS study, from 2014 to 2017, to compare Vitamin A levels and MS progression. All data was collected from a single clinical site. Demographic data as well as date of diagnosis and use of disease modifying therapies. Patients not able to obtain MRIs or lab tests and histories of vitamin abnormalities were excluded from the study. 29 patients met inclusion criteria. We chose presenting symptoms of vision, balance, sensory function, and motor function as these represented the most common manifestations of the disease and mirror the domains of the EDSS, which is the most commonly used scale for MS disease severity. We also included neuroimaging based lesion volume as another objective measure for comparison. Results: Although duration of disease was different between comparator groups, no significant difference was found between them when EDSS and lesion volumes were compared. There was a difference in lesion volumes when comparing those patients that had presenting symptoms of visual changes or balance symptoms with those presenting with sensory changes. Conclusions: This study supports the notion that presenting symptoms are not associated with EDSS independent disease duration. It also verifies that severity of disease is not associated with lesion volumes. However, sensory symptoms as a presenting symptom was associated with less lesion volumes in our study.
Perceived Nutrition and Health Concerns: Do They Protect against Unhealthy Dietary Patterns in Polish Adults?
Authors: Drywień Małgorzata Ewa , Hamulka Jadwiga , Jezewska-Zychowicz Marzena
Published: January 2021

The aim of the study was to explore the associations between perceived health and nutrition concerns, sociodemographic characteristics and unhealthy dietary patterns in a representative group of Polish adults. The data were collected in 2017 through a cross-sectional quantitative survey under the National Health Program 2016–2020. Logistic regression models were used to analyze the data. It was found that higher health concerns decreased the chances of adhering to upper tertiles of “Fast food & alcohol” and “Refined food & sweetened beverages” dietary patterns (DPs), thus displaying less frequent consumption of such foods. No relationship was found between health concerns and adhering to the “Fat food” and “Butter” DPs. Nutrition concerns increased the likelihood of frequent consumption of foods from “Fast food & alcohol” DP. Women were less likely to adhere to unhealthy eating patterns than men, while older people were less likely to often consume fast food, alcohol, or refined food and sweetened beverages. Findings of this study showed that concerns about health or nutrition were differently associated with dietary patterns and consumption of unhealthy foods. These relationships should be considered when developing interventions to address health-related lifestyle changes. However, further research is needed to identify cause-effect relationships between these variables.
Diet Modifications in Primary Prevention of Asthma. Where Do We Stand?
Authors: Sozańska Barbara , Sikorska-Szaflik Hanna
Published: January 2021

The steep increase in asthma prevalence, observed worldwide in recent decades, has created an urgent need to search for effective methods of its prevention. Among other environmental factors, changes in diet habits and the potential influence of individual food components on immunological processes have been extensively studied as a potential method of intervention in primary prevention of asthma. The preventive role of some nutrients has been confirmed: unpasteurized milk reduced the risk of asthma in epidemiological studies, vitamin D supplementation was effective in preventing the transient forms of wheezing in small children and high maternal intake of fish oil reduced the risk of persistent wheeze and asthma in children. However, not all studies provided consistent results, and many food ingredients are still pending for defining their role in asthma development. Moreover, a novel approach looking not only at single food ingredients, but the whole dietary patterns and diversity has recently been proposed. In this paper, we discuss the current role of nutrients in asthma primary prevention and the reasons for inconsistencies in the study results. We look at single diet components, but also the whole dietary patterns. We describe the proposed mechanisms of action at different stages of life, identify the role of modifiers and delineate future perspectives on the application of nutrients in targeting strategies for asthma primary prevention.
Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease
Authors: Monachesi Chiara , Verma Anil K. , Catassi Giulia N. , Galeazzi Tiziana , Franceschini Elisa , Perticaroli Valentina , Lionetti Elena , Catassi Carlo
Published: January 2021

A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2–18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5–20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.
Can Monitoring Make It Happen? An Assessment of How Reporting, Monitoring, and Evaluation Can Support Local Wellness Policy Implementation in US Schools
Authors: Turner Lindsey , Asada Yuka , Leider Julien , Piekarz-Porter Elizabeth , Schwartz Marlene , Chriqui Jamie F.
Published: January 2021

US school districts participating in federal child nutrition programs are required to develop a local wellness policy (LWP). Each district is allowed flexibility in policy development, including the approaches used for policy reporting, monitoring, and evaluation (RME). The aim of this convergent mixed-methods study was to quantitatively examine RME provisions in policies among a nationally representative sample of districts in the 2014–2015 school year in order to examine whether policies were associated with RME practices in those districts, and to qualitatively examine perceived challenges to RME practices. Data were compiled through the School Nutrition and Meal Cost Study and the National Wellness Policy Study. In multivariable regression models accounting for demographics, survey respondents were significantly more likely to report that their district had informed the public about LWP content and implementation, if there was a relevant policy provision in place. Having a strong policy (as compared to no policy) requiring evaluation was associated with reports that the district had indeed evaluated implementation. Having definitive/required provisions in policies was significantly associated with actual use of RME practices. RME activities are an important part of policy implementation, and these results show that policy provisions addressing RME activities must be written with strong language to require compliance. In interviews with 39 superintendents, many reported that RME activities are challenging, including difficulty determining how to monitor and show impact of their district’s wellness initiatives. Furthermore, the qualitative results highlighted the need for vetted tools that are freely available, widely used, and feasible for districts to use in assessing their progress toward meeting the goals in their LWPs.
Influence of the Seasonal Thermocline on the Vertical Distribution of Larval Fish Assemblages Associated with Atlantic Bluefin Tuna Spawning Grounds
Authors: Alvarez Itziar , Rasmuson Leif K. , Gerard Trika , Laiz-Carrion Raul , Hidalgo Manuel , Lamkin John T. , Malca Estrella , Ferra Carmen , Torres Asvin P. , Alvarez-Berastegui Diego , Alemany Francisco , Quintanilla Jose M. , Martin Melissa , Rodriguez Jose M. , Reglero Patricia
Published: January 2021

Temperature is often an important variable influencing the vertical position of fish larvae in the water column. The same species may show different vertical distributions in areas with a strong near-surface seasonal thermocline compared to isothermal near-surface regions. In areas with a strong surface thermocline, tuna larvae show a significant preference for the near-surface warmer layers. Little is known regarding larval tuna vertical distribution in isothermal waters and on the vertical distribution of the associated larval fish assemblages. We conducted vertical stratified sampling using the same methodology and fishing device (MOCNESS) in the two major spawning areas of Atlantic bluefin tuna (BFT): western Mediterranean Sea (MED), characterized by a surface thermocline, and the Gulf of Mexico (GOM) which lacks thermal stratification. Tuna larvae occupied the upper 30 m in both areas, but the average larval depth distribution was consistently deeper in the GOM. In the MED, vertical distribution of larval fish assemblages was explained by temperature, and species such as BFT, Thunnus alalunga, and Ceratoscopelus maderensis, among others, coexist above the thermocline and are separated from species such as Cyclothone braueri and Hygophum spp. (found below the thermocline). In the GOM, the environmental correlates of the vertical distribution of the larvae were salinity and fluorescence. Mesopelagic taxa such as Ceratoscopelus spp. and Cyclothone spp., among others, had a shallower average distribution than Lampanyctus spp., Hygophum spp., and Myctophum spp.
Synthetic Inhibitors of CDK4/6 Activities and Tumor Suppression: A Preface to the Special Issue
Authors: Takahashi Chiaki , Kato Jun-ya
Published: January 2021

The status of RB1 in cancer may help us determine the optimal therapeutic approach to patients [...]
Triatomine Feeding Profiles and Trypanosoma cruzi Infection, Implications in Domestic and Sylvatic Transmission Cycles in Ecuador
Authors: Ocaña-Mayorga Sofía , Bustillos Juan José , Villacís Anita G. , Pinto C. Miguel , Brenière Simone Frédérique , Grijalva Mario J.
Published: January 2021

Understanding the blood meal patterns of insects that are vectors of diseases is fundamental in unveiling transmission dynamics and developing strategies to impede or decrease human–vector contact. Chagas disease has a complex transmission cycle that implies interactions between vectors, parasites and vertebrate hosts. In Ecuador, limited data on human infection are available; however, the presence of active transmission in endemic areas has been demonstrated. The aim of this study was to determine the diversity of hosts that serve as sources of blood for triatomines in domestic, peridomestic and sylvatic transmission cycles, in two endemic areas of Ecuador (central coastal and southern highland regions). Using conserved primers and DNA extracted from 507 intestinal content samples from five species of triatomines (60 Panstrongylus chinai, 17 Panstrongylus howardi, 1 Panstrongylus rufotuberculatus, 427 Rhodnius ecuadoriensis and 2 Triatoma carrioni) collected from 2006 to 2013, we amplified fragments of the cytb mitochondrial gene. After sequencing, blood meal sources were identified in 416 individuals (146 from central coastal and 270 from southern highland regions), achieving ≥ 95% identity with GenBank sequences (NCBI-BLAST tool). The results showed that humans are the main source of food for triatomines, indicating that human–vector contact is more frequent than previously thought. Although other groups of mammals, such as rodents, are also an available source of blood, birds (particularly chickens) might have a predominant role in the maintenance of triatomines in these areas. However, the diversity of sources of blood found might indicate a preference driven by triatomine species. Moreover, the presence of more than one source of blood in triatomines collected in the same place indicated that dispersal of vectors occurs regardless the availability of food. Dispersal capacity of triatomines needs to be evaluated to propose an effective strategy that limits human–vector contact and, in consequence, to decrease the risk of T. cruzi transmission.
Canine Distemper Outbreak by Natural Infection in a Group of Vaccinated Maned Wolves in Captivity
Authors: Vergara-Wilson Vicente , Hidalgo-Hermoso Ezequiel , Sanchez Carlos R. , Abarca María J. , Navarro Carlos , Celis-Diez Sebastian , Soto-Guerrero Pilar , Diaz-Ayala Nataly , Zordan Martin , Cifuentes-Ramos Federico , Cabello-Stom Javier
Published: January 2021

Canine distemper virus (CDV) is one of the most significant infectious disease threats to the health and conservation of free-ranging and captive wild carnivores. CDV vaccination using recombinant canarypox-based vaccines has been recommended for maned wolf (Chrysocyon brachyurus) after the failure of modified live vaccines that induced disease in vaccinated animals. Here, we report a CDV outbreak in a captive population of maned wolves that were previously vaccinated. Five juveniles and one adult from a group of seven maned wolves housed in an outdoor exhibit died in April–May 2013 in a zoo in the Metropolitan Region, Chile. Clinical signs ranged from lethargy to digestive and respiratory signs. Diagnosis of CDV was confirmed by histopathology, antibody assays, and viral molecular detection and characterization. The phylogenetic analyses of the nucleotide sequence of the H gene of the CDV genome identified in the two positive samples suggest a close relation with the lineage Europe 1, commonly found in South America and Chile. CDV infections in maned wolves have not been previously characterized. To the authors’ best knowledge, this is the first report of the clinical presentation of CDV in a canine species previously immunized with a recombinant vaccine.
Emerging Infectious Diseases in Pregnant Women in a Non-Endemic Area: Almost One Out of Four Is at Risk
Authors: Modi Giulia , Borchi Beatrice , Giaché Susanna , Campolmi Irene , Trotta Michele , Di Tommaso Mariarosaria , Strambi Noemi , Bartoloni Alessandro , Zammarchi Lorenzo
Published: January 2021

We report the results of a targeted testing strategy for five emerging infectious diseases (Chagas disease, human T-lymphotropic virus 1 infection, malaria, schistosomiasis, and Zika virus infection) in pregnant women accessing an Italian referral centre for infectious diseases in pregnancy for unrelated reasons. The strategy is based on a quick five-question questionnaire which allows the identification of pregnant women at risk who should be tested for a specific disease. One hundred and three (24%) out of 429 pregnant women evaluated in a 20 month period were at risk for at least one emerging infectious disease. Three (2.9%, all from sub-Saharan Africa) out of 103 at-risk women resulted in being affected (one case of Plasmodium falciparum malaria, two cases of schistosomiasis) and were appropriately managed. Prevalence of emerging infectious disease was particularly high in pregnant women from Africa (three out of 25 pregnant women tested, 12%). The proposed strategy could be used by health care professionals managing pregnant women in non-endemic setting, to identify those at risk for one of the five infection which could benefit for a targeted test and treatment.
Human Herpesvirus 6A Induces Dendritic Cell Death and HMGB1 Release without Virus Replication
Authors: Gustafsson Rasmus
Published: January 2021

Human herpesvirus 6A (HHV-6A) is a common virus that has important immunomodulatory effects. Dendritic cells (DC) are key players in innate and adaptive immunity and are implicated in the pathogenesis of many human diseases, including infections. (1) Background: Previous studies have demonstrated suppressive effects of HHV-6A on key DC functions. (2) Methods: human monocyte derived dendritic cells were inoculated with HHV-6A and viral replication, cell viability, and release of high mobility group box 1 (HMGB1) protein from DC and of the cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ after co-culture with allogenic CD4+ T cells were assessed. (3) Results: Nonproductive infection of HHV-6A in DC leads to titer-dependent cell death and the release of HMGB1 protein, and a Th2 polarization. (4) Conclusion: These immune responses aimed to clear the infection may also imply risks for inflammatory pathologies associated with HHV-6A such as multiple sclerosis.
Systemic Inflammatory Index Is a Novel Predictor of Intubation Requirement and Mortality after SARS-CoV-2 Infection
Authors: Muhammad Sajjad , Fischer Igor , Naderi Soheil , Faghih Jouibari Morteza , Abdolreza Sheikhrezaei , Karimialavijeh Ehsan , Aslzadeh Sara , Mashayekhi Mahsa , Zojaji Mohaddeseh , Kahlert Ulf Dietrich , Hänggi Daniel
Published: January 2021

Coronavirus disease 2019 (COVID-19), with an increasing number of deaths worldwide, has created a tragic global health and economic emergency. The disease, caused by severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-19), is a multi-system inflammatory disease with many of COVID-19-positive patients requiring intensive medical care due to multi-organ failures. Biomarkers to reliably predict the patient’s clinical cause of the virus infection, ideally, to be applied in point of care testing or through routine diagnostic approaches, are highly needed. We aimed to probe if routinely assessed clinical lab values can predict the severity of the COVID-19 course. Therefore, we have retrospectively analyzed on admission laboratory findings in 224 consecutive patients from four hospitals and show that systemic immune inflammation index (SII) is a potent marker for predicting the requirement for invasive ventilator support and for worse clinical outcome of the infected patient. Patients’ survival and severity of SARS-CoV-2 infection could reliably be predicted at admission by calculating the systemic inflammatory index of individual blood values. We advocate this approach to be a feasible and easy-to-implement assay that may be particularly useful to improve patient management during high influx crisis. We believe with this work to contribute to improving infrastructure availability and case management associated with COVID-19 pandemic hurdles.
Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player
Authors: Dinparastisaleh Roshan , Mirsaeidi Mehdi
Published: January 2021

The melanocortin system encompasses melanocortin peptides, five receptors, and two endogenous antagonists. Besides pigmentary effects generated by α-Melanocytic Hormone (α-MSH), new physiologic roles in sexual activity, exocrine secretion, energy homeostasis, as well as immunomodulatory actions, exerted by melanocortins, have been described recently. Among the most common and burdensome consequences of chronic inflammation is the development of fibrosis. Depending on the regenerative capacity of the affected tissue and the quality of the inflammatory response, the outcome is not always perfect, with the development of some fibrosis. Despite the heterogeneous etiology and clinical presentations, fibrosis in many pathological states follows the same path of activation or migration of fibroblasts, and the differentiation of fibroblasts to myofibroblasts, which produce collagen and α-SMA in fibrosing tissue. The melanocortin agonists might have favorable effects on the trajectories leading from tissue injury to inflammation, from inflammation to fibrosis, and from fibrosis to organ dysfunction. In this review we briefly summarized the data on structure, receptor signaling, and anti-inflammatory and anti-fibrotic properties of α-MSH and proposed that α-MSH analogues might be promising future therapeutic candidates for inflammatory and fibrotic diseases, regarding their favorable safety profile.
A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies
Authors: Arranz-Romera Alicia , Hernandez Maria , Checa-Casalengua Patricia , Garcia-Layana Alfredo , Molina-Martinez Irene T. , Recalde Sergio , Young Michael J. , Tucker Budd A. , Herrero-Vanrell Rocío , Fernandez-Robredo Patricia , Bravo-Osuna Irene
Published: January 2021

We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.
Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid
Authors: Kang Yun Ju , Lee Chul Haeng , Park Soo-Jin , Lee Hye Suk , Choi Min-Koo , Song Im-Sook
Published: January 2021

We investigated the involvement of drug transporters in the pharmacokinetics of rosmarinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a Km of 26.5 μM and a Vmax of 69.0 pmol/min in HEK293 cells overexpressing OAT1, and the plasma concentrations of rosmarinic acid were increased by the co-injection of probenecid because of decreased renal excretion due to OAT1 inhibition. Rosmarinic acid inhibited the transport activities of OAT1, OAT3, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 with IC50 values of 60.6 μM, 1.52 μM, 74.8 μM, and 91.3 μM, respectively, and the inhibitory effect of rosmarinic acid on OAT3 transport activity caused an in vivo pharmacokinetic interaction with furosemide by inhibiting its renal excretion and by increasing its plasma concentration. In conclusion, OAT1 and OAT3 are the major transporters that may regulate the pharmacokinetic properties of rosmarinic acid and may cause herb-drug interactions with rosmarinic acid, although their clinical relevance awaits further evaluation.
Cyclodextrin Diethyldithiocarbamate Copper II Inclusion Complexes: A Promising Chemotherapeutic Delivery System against Chemoresistant Triple Negative Breast Cancer Cell Lines
Authors: Said Suliman Ammar , Khoder Mouhamad , Tolaymat Ibrahim , Webster Matt , Alany Raid G. , Wang Weiguang , Elhissi Abdelbary , Najlah Mohammad
Published: January 2021

Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.
Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues
Authors: Xiroudaki Styliani , Ianni Federica , Sabbatini Samuele , Roselletti Elena , Monari Claudia , Sardella Roccaldo , Vecchiarelli Anna , Giovagnoli Stefano
Published: January 2021

In this study, an initial in vivo evaluation of a new amikacin-deoxycholate hydrophobic salt aimed at potentiating amikacin action against hard-to-treat lung infections was undertaken by quantifying, for the first time, amikacin in whole blood. Pharmacokinetic evaluation after intranasal administration in a murine model showed higher drug retention in the lungs compared to blood, with no significant differences between the salt and the free drug. Upon repeated administrations, the two treatments resulted in nonsignificant tissue damage and mild higher inflammation for the hydrophobic salt. Whole-blood analysis highlighted an unreported high partition of amikacin in blood components up to 48 h, while significant lung levels were measured up to 72 h. Such a new observation was considered responsible for the nearly overlapping pharmacokinetic profiles of the two treatments. To overcome such an issue, a dry powder in an inhalable form may be best suited. Moreover, if confirmed in humans, and considering the current once-a-day regimen for amikacin aerosols, important yet-to-be-explored clinical implications may be postulated for such amikacin persistence in the organism.
Use of Concept Mapping to Identify Expectations of Pharmacy Students Selecting Elective Courses
Authors: Vinall Ruth , Balan Peter
Published: January 2021

The objective of this study was to demonstrate the use of concept mapping as a method for analyzing pharmacy students’ qualitative perceptions of their expectations of elective courses and to thus help guide delivery methods and course content. A survey containing demographic, Likert scale, and open-ended questions was administered to second-year pharmacy students prior to the start of elective courses and an innovative methodology, concept mapping, was used to identify major themes relating to student expectations. The association between preferred class delivery method (online versus in person) with student gender and English-as-a-second-language status (ESL) was also assessed. Note that this study was conducted prior to the COVID-19 pandemic. Ninety-eight out of 133 students (74%) completed the survey. Overall, 56% students stated that they preferred online delivery of courses (68% of these students were female, 36% were male). ESL status did not impact preference. The most common themes relating to student course expectations were the desire to learn about the elective course topic as well “real-world” utility. Our combined data indicate that delivery method is a key factor contributing to students’ choice of elective course and that concept mapping is an effective and efficient way to help identify student expectations of elective courses.
Network Analysis of the Interaction between Different Religious and Philosophical Movements in Early Judaism
Authors: Tantlevskij Igor R. , Gromova Ekaterina V. , Gromov Dmitry
Published: January 2021

This paper presents an attempt to systematically describe and interpret the evolution of different religious and political movements in Judaea during the period of the Second Temple using the methods of the theory of social networks. We extensively analyzed the relationship between the main Jewish sects: Pharisees, Sadducees, Essenes (Qumranites), and later also Zealots. It is shown that the evolution of the relations between these sects agreed with the theory of social balance and their relations evolved toward more socially balanced structures.
V-Substituted ZnIn2S4: A (Visible+NIR) Light-Active Photocatalyst
Authors: Lucena Raquel , Conesa José C.
Published: January 2021

ZnIn2S4 is known to be a visible light-active photocatalyst. In this work, it is shown that by substituting part of the In atoms with vanadium, the visible light range of photocatalytic activity of such material can be extended, using the so-called in-gap band scheme that has been shown to enhance photovoltaic characteristics. Characterization of this material using several techniques, complemented by DFT calculations, will support this statement. While here only the degradation of aqueous HCOOH in well-aerated conditions is discussed, the same material may be used, with an adequate sacrificial reagent, for photocatalytic H2 generation.
Recent Advances in High Speed Photodetectors for eSWIR/MWIR/LWIR Applications
Authors: Chen Baile , Chen Yaojiang , Deng Zhuo
Published: January 2021

High speed photodetectors operating at a telecommunication band (from 1260 to 1625 nm) have been well studied with the development of an optical fiber communication system. Recent innovations of photonic systems have raised new requirements on the bandwidth of photodetectors with cutoff wavelengths from extended short wavelength infrared (eSWIR) to long wavelength infrared (LWIR). However, the frequency response performance of photodetectors in these longer wavelength bands is less studied, and the performances of the current high-speed photodetectors in these bands are still not comparable with those in the telecommunication band. In this paper, technical routes to achieve high response speed performance of photodetectors in the extended short wavelength infrared/mid wavelength infrared/long wavelength infrared (eSWIR/MWIR/LWIR) band are discussed, and the state-of-the-art performances are reviewed.
Dissecting Hierarchies between Light, Sugar and Auxin Action Underpinning Root and Root Hair Growth
Authors: García-González Judith , Lacek Jozef , Retzer Katarzyna
Published: January 2021

Plant roots are very plastic and can adjust their tissue organization and cell appearance during abiotic stress responses. Previous studies showed that direct root illumination and sugar supplementation mask root growth phenotypes and traits. Sugar and light signaling where further connected to changes in auxin biosynthesis and distribution along the root. Auxin signaling underpins almost all processes involved in the establishment of root traits, including total root length, gravitropic growth, root hair initiation and elongation. Root hair plasticity allows maximized nutrient uptake and therefore plant productivity, and root hair priming and elongation require proper auxin availability. In the presence of sucrose in the growth medium, root hair emergence is partially rescued, but the full potential of root hair elongation is lost. With our work we describe a combinatory study showing to which extent light and sucrose are antagonistically influencing root length, but additively affecting root hair emergence and elongation. Furthermore, we investigated the impact of the loss of PIN-FORMED2, an auxin efflux carrier mediating shootward auxin transporter, on the establishment of root traits in combination with all growth conditions.
Incorporation of Poly(Itaconic Acid) with Quaternized Thiazole Groups on Gelatin-Based Films for Antimicrobial-Active Food Packaging
Authors: Cottet Celeste , Salvay Andrés G. , Peltzer Mercedes A. , Fernández-García Marta
Published: January 2021

Poly(itaconic acid) (PIA) was synthesized via conventional radical polymerization. Then, functionalization of PIA was carried out by an esterification reaction with the heterocyclic groups of 1,3-thiazole and posterior quaternization by N-alkylation reaction with iodomethane. The modifications were confirmed by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1H-NMR), as well as ζ-potential measurements. Their antimicrobial activity was tested against different Gram-negative and Gram-positive bacteria. After characterization, the resulting polymers were incorporated into gelatin with oxidized starch and glycerol as film adjuvants, and dopamine as crosslinking agent, to develop antimicrobial-active films. The addition of quaternized polymers not only improved the mechanical properties of gelatin formulations, but also decreased the solution absorption capacity during the swelling process. However, the incorporation of synthesized polymers increased the deformation at break values and the water vapor permeability of films. The antioxidant capacity of films was confirmed by radical scavenging ability and, additionally, those films exhibited antimicrobial activity. Therefore, these films can be considered as good candidates for active packaging, ensuring a constant concentration of the active compound on the surface of the food, increasing products’ shelf-life and reducing the environmental impact generated by plastics of petrochemical origin.