bluuebunny/crossref_metadata_2025 huggingface dataset:
Knee Wear Assessment: 3D Scanners Used as a Consolidated Procedure
Authors: Affatato Saverio , Valigi Maria Cristina , Logozzo Silvia
Published: May 2020

It is well known that wear occurring in polyethylene menisci is a significant clinical problem. At this regard, wear tests on biomaterials medical devices are performed in order to assess their pre-clinical performance in terms of wear, durability, resistance to fatigue, etc. The objective of this study was to assess the wear of mobile total knee polyethylene inserts after an in vitro wear test. In particular, the wear behavior of mobile bearing polyethylene knee configurations was investigated using a knee joint wear simulator. After the completion of the wear test, the polyethylene mobile menisci were analyzed through a consolidated procedure by using 3D optical scanners, in order to evaluate the 3D wear distribution on the prosthesis surface, wear depths, wear rates, amount of material loss and contact areas. The results in terms of wear rates and wear volumes were compared with results of gravimetric tests, finding equivalent achievements.
Low-Cost Method and Biochip for Measuring the Trans-Epithelial Electrical Resistance (TEER) of Esophageal Epithelium
Authors: Poenar Daniel Puiu , Yang Guang , Wan Wei Keat , Feng Shilun
Published: May 2020

Trans-epithelial electrical resistance (TEER) is a good indicator of the barrier integrity of epithelial tissues and is often employed in biomedical research as an effective tool to assess ion transport and permeability of tight junctions. The Ussing chamber is the gold standard for measuring TEER of tissue specimens, but it has major drawbacks: it is a macroscopic method that requires a careful and labor intensive sample mounting protocol, allows a very limited viability for the mounted sample, has large parasitic components and low throughput as it cannot perform multiple simultaneous measurements, and this sophisticated and delicate apparatus has a relatively high cost. This paper demonstrates a low-cost home-made “sandwich ring” method which was used to measure the TEER of tissue specimens effectively. This method inspired the subsequent design of a biochip fabricated using standard soft lithography and laser engraving technologies, with which the TEER of pig epithelial tissues was measured. Moreover, it was possible to temporarily preserve the tissue specimens for days in the biochip and monitor the TEER continuously. Tissue responses after exposure tests to media of various pH values were also successfully recorded using the biochip. All these demonstrate that this biochip could be an effective, cheaper, and easier to use Ussing chamber substitute that may have relevant applications in clinical practice.
Fish-Based Bioactives as Potent Nutraceuticals: Exploring the Therapeutic Perspective of Sustainable Food from the Sea
Authors: Ashraf Syed Amir , Adnan Mohd , Patel Mitesh , Siddiqui Arif Jamal , Sachidanandan Manojkumar , Snoussi Mejdi , Hadi Sibte
Published: May 2020

Recent developments in nutraceuticals and functional foods have confirmed that bioactive components present in our diet play a major therapeutic role against human diseases. Moreover, there is a huge emphasis on food scientists for identifying and producing foods with better bioactive activity, which can ultimately provide wellness and well-being to human health. Among the several well-known foods with bioactive constituents, fish has always been considered important, due to its rich nutritional values and by-product application in food industries. Nutritionists, food scientists, and other scientific communities have been working jointly to uncover new bioactive molecules that could increase the potential and therapeutic benefits of these bioactive components. Despite the innumerable benefits of fish and known fish bioactive molecules, its use by food or pharmaceutical industries is scarce, and even research on fish-based nutraceuticals is not promising. Therefore, this review focuses on the current information/data available regarding fish bioactive components, its application as nutraceuticals for therapeutic purposes in the treatment of chronic diseases, ethnic issues related to consumption of fish or its by-products. Especial emphasis is given on the utilization of fish wastes and its by-products to fulfill the world demand for cheap dietary supplements specifically for underdeveloped/least developed countries.
The Role of Laparoscopic Ultrasonography in the Evaluation of Suspected Choledocholithiasis. A Single-Center Experience
Authors: Atstupens Kristaps , Mukans Maksims , Plaudis Haralds , Pupelis Guntars
Published: May 2020

Background and objectives: Opinions differ regarding the optimal diagnostic methods for patients with suspected choledocholithiasis. The aim of this study was to assess the diagnostic accuracy of laparoscopic ultrasonography (LUS) and compare it to pre-operative magnetic resonance cholangio-pancreatography (MRCP); Materials and Methods: In all patients with suspected choledocholithiasis LUS was performed during laparoscopic cholecystectomy to evaluate biliary stones. According to availability, part of the patients had pre-operative MRCP. Data for diagnostic accuracy and main outcomes were collected prospectively and analyzed retrospectively; Results: Choledocholithiasis was detected in 178 of 297 patients by LUS (59.93%) and in 39 of 87 patients by MRCP (44.8%), p = 0.041. LUS yielded a sensitivity of 99.4%, a specificity of 94.3%, a positive predictive value of 96.1% and a negative predictive value of 99.1%. However, pre-operative MRCP had a sensitivity of 61.7%, a specificity of 92.3%, a positive predictive value of 94.9% and a negative predictive value of 51.1%. Moreover, of the 47 patients with no choledocholithiasis by MRCP, in 23 cases it was later detected by LUS (a false negative MRCP finding—38.3%), p < 0.001. Median duration of hospitalization was significantly shorter in patients evaluated without pre-operative MRCP—8 days (interquartile range – IQR 11–6) vs. 11 days (IQR 14–9), p = 0.001; Conclusions: LUS may reduce the role of pre-operative MRCP and can become a rational alternative to MRCP as a primary imaging technique for the detection of choledocholithiasis.
COVID-19 Pandemic and Telephone Triage before Attending Medical Office: Problem or Opportunity?
Authors: Cervino Gabriele , Oteri Giacomo
Published: May 2020

During the COVID-19 emergency, the medical operating protocols have been largely modified for reducing any type of contamination risk, for working in a safe way and for making the patient feel in a safe environment. Telemedicine, smart phones and apps could represent important devices for the community, in order to prevent virus trasmission and to perform quick diagnosis and management at medical offices. This manuscript could be useful for clinicians with regard to the current state of the effectiveness of the telephone triage in this COVID-19 epidemic period. Therefore, it could be an important starting point for future perspectives about telemedicine and virtual patient management.
Hybrid Process Chain for the Integration of Direct Ink Writing and Polymer Injection Molding
Authors: Loaldi Dario , Piccolo Leonardo , Brown Eric , Tosello Guido , Shemelya Corey , Masato Davide
Published: May 2020

The integration of additive manufacturing direct-writing technologies with injection molding provides a novel method to combine functional features into plastic products, and could enable mass-manufacturing of custom-molded plastic parts. In this work, direct-write technology is used to deposit conductive ink traces on the surface of an injection mold. After curing on the mold surface, the printed trace is transferred into the plastic part by exploiting the high temperature and pressure of a thermoplastic polymer melt flow. The transfer of the traces is controlled by interlocking with the polymer system, which creates strong plastic/ink interfacial bonding. The hybrid process chain uses designed mold/ink surface interactions to manufacture stable ink/polymer interfaces. Here, the process chain is proposed and validated through systematic interfacial analysis including feature fidelity, mechanical properties, adhesion, mold topography, surface energy, and hot polymer contact angle.
Liquid Chromatographic Tandem Mass Spectrometric (LC-MS/MS) Determination of Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) in the Yolk of Poultry Eggs in Malaysia
Authors: Tahziz Atiqah , Mohamad Haron Didi Erwandi , Aziz Mohd Yusmaidie
Published: May 2020

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are widely used in products, and are known for their water and grease repellent properties. The persistence nature and potential toxicity of these substances have raised substantial concerns about health effects. Regarding humans, food consumption has reportedly been a significant source of exposure for both compounds. Hence, this study was performed to develop and validate an analytical method for PFOS and PFOA in egg yolks using liquid chromatographic tandem mass spectrometry (LC-MS/MS) followed by the determination of concentration of both compounds in the yolk of poultry eggs in Malaysia. A total of 47 poultry egg yolk samples were extracted by a simple protein precipitation technique using acetonitrile. The analytical method was developed using LC-MS/MS and validated based on the Food and Drug Administration (FDA)’s Bioanalytical Method Validation guidelines. The results revealed that PFOS was quantitatively detected in six samples, with the concentration range between 0.5 and 1.01 ng g−1. Among these, five samples were from home-produced chicken eggs, and one sample was from a quail egg. The levels of PFOA in all samples were below the quantifiable limit (<0.1 ng g−1). This indicated that the contamination of PFCs in poultry eggs were mostly attributed to the nature of free foraging animals, which had direct contact with the contaminants in soil and feed. In conclusion, a fast and robust analytical method for analyzing PFOS and PFOA in egg yolk samples using LC-MS/MS was successfully developed and validated. The presence of these emerging contaminants in this study signified widespread pollution in the environment.
In Vitro Investigations of Acetohexamide Binding to Glycated Serum Albumin in the Presence of Fatty Acid
Authors: Szkudlarek Agnieszka , Wilk Michał , Maciążek-Jurczyk Małgorzata
Published: May 2020

The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.
Sulfur Compounds Inhibit High Glucose-Induced Inflammation by Regulating NF-κB Signaling in Human Monocytes
Authors: Jo Eun Seong , Sp Nipin , Kang Dong Young , Rugamba Alexis , Kim Il Ho , Bae Se Won , Liu Qing , Jang Kyoung-Jin , Yang Young Mok
Published: May 2020

High glucose-induced inflammation leads to atherosclerosis, which is considered a major cause of death in type 1 and type 2 diabetic patients. Nuclear factor-kappa B (NF-κB) plays a central role in high glucose-induced inflammation and is activated through toll-like receptors (TLRs) as well as canonical and protein kinase C-dependent (PKC) pathways. Non-toxic sulfur (NTS) and methylsulfonylmethane (MSM) are two sulfur-containing natural compounds that can induce anti-inflammation. Using Western blotting, real-time polymerase chain reaction, and flow cytometry, we found that high glucose-induced inflammation occurs through activation of TLRs. An effect of NTS and MSM on canonical and PKC-dependent NF-κB pathways was also demonstrated by western blotting. The effects of proinflammatory cytokines were investigated using a chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. Our results showed inhibition of the glucose-induced expression of TLR2 and TLR4 by NTS and MSM. These sulfur compounds also inhibited NF-κB activity through reactive oxygen species (ROS)-mediated canonical and PKC-dependent pathways. Finally, NTS and MSM inhibited the high glucose-induced expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and binding of NF-κB protein to the DNA of proinflammatory cytokines. Together, these results suggest that NTS and MSM may be potential drug candidates for anti-inflammation therapy.
Tyrosinase Inhibition and Kinetic Details of Puerol A Having But-2-Enolide Structure from Amorpha fruticosa
Authors: Kim Jeong Ho , Jang Da Hyun , Lee Ki Won , Kim Kwang Dong , Shah Abdul Bari , Zhumanova Kamila , Park Ki Hun
Published: May 2020

Puerol A (1) from Amorpha fruticosa showed highly potent inhibition against both monophenolase (IC50 = 2.2 μM) and diphenolase (IC50 = 3.8 μM) of tyrosinase. We tried to obtain a full story of enzyme inhibitory behavior for inhibitor 1 because the butenolide skeleton has never been reported as a tyrosinase inhibitor. Puerol A was proved as a reversible, competitive, simple slow-binding inhibitor, according to the respective parameters; k3 = 0.0279 μM−1 min−1 and k4 = 0.003 min−1. A longer lag-phase and a reduced static-state activity of the enzyme explained that puerol A had a tight formation of the complex with Emet. Dose-dependent inhibition was also confirmed by high-performance liquid chromatography (HPLC) analysis using N-acetyl-l-tyrosine as a substrate, which was completely inhibited at 20 μM. A high binding affinity of 1 to tyrosinase was confirmed by fluorescence quenching analysis. Moreover, puerol A decreased melanin content in the B16 melanoma cell dose-dependently with an IC50 of 11.4 μM.
Hypoxia-Activated Prodrug Derivatives of Carbonic Anhydrase Inhibitors in Benzenesulfonamide Series: Synthesis and Biological Evaluation
Authors: Anduran Emilie , Aspatwar Ashok , Parvathaneni Nanda-Kumar , Suylen Dennis , Bua Silvia , Nocentini Alessio , Parkkila Seppo , Supuran Claudiu T. , Dubois Ludwig , Lambin Philippe , Winum Jean-Yves
Published: May 2020

Hypoxia, a common feature of solid tumours’ microenvironment, is associated with an aggressive phenotype and is known to cause resistance to anticancer chemo- and radiotherapies. Tumour-associated carbonic anhydrases isoform IX (hCA IX), which is upregulated under hypoxia in many malignancies participating to the microenvironment acidosis, represents a valuable target for drug strategy against advanced solid tumours. To overcome cancer cell resistance and improve the efficacy of therapeutics, the use of bio-reducible prodrugs also known as Hypoxia-activated prodrugs (HAPs), represents an interesting strategy to be applied to target hCA IX isozyme through the design of selective carbonic anhydrase IX inhibitors (CAIs). Here, we report the design, synthesis and biological evaluations including CA inhibition assays, toxicity assays on zebrafish and viability assays on human cell lines (HT29 and HCT116) of new HAP-CAIs, harboring different bio-reducible moieties in nitroaromatic series and a benzenesulfonamide warhead to target hCA IX. The CA inhibition assays of this compound series showed a slight selectivity against hCA IX versus the cytosolic off-target hCA II and hCA I isozymes. Toxicity and viability assays have highlighted that the compound bearing the 2-nitroimidazole moiety possesses the lowest toxicity (LC50 of 1400 µM) and shows interesting results on viability assays.
Potential Plasticity of the Mannoprotein Repertoire Associated to Mycobacterium tuberculosis Virulence Unveiled by Mass Spectrometry-Based Glycoproteomics
Authors: Tonini Laure , Sadet Bashir , Stella Alexandre , Bouyssié David , Nigou Jérôme , Burlet-Schiltz Odile , Rivière Michel
Published: May 2020

To date, Mycobacterium tuberculosis (Mtb) remains the world’s greatest infectious killer. The rise of multidrug-resistant strains stresses the need to identify new therapeutic targets to fight the epidemic. We previously demonstrated that bacterial protein-O-mannosylation is crucial for Mtb infectiousness, renewing the interest of the bacterial-secreted mannoproteins as potential drug-targetable virulence factors. The difficulty of inventorying the mannoprotein repertoire expressed by Mtb led us to design a stringent multi-step workflow for the reliable identification of glycosylated peptides by large-scale mass spectrometry-based proteomics. Applied to the differential analyses of glycoproteins secreted by the wild-type Mtb strain—and by its derived mutant invalidated for the protein-O-mannosylating enzyme PMTub—this approach led to the identification of not only most already known mannoproteins, but also of yet-unknown mannosylated proteins. In addition, analysis of the glycoproteome expressed by the isogenic recombinant Mtb strain overexpressing the PMTub gene revealed an unexpected mannosylation of proteins, with predicted or demonstrated functions in Mtb growth and interaction with the host cell. Since in parallel, a transient increased expression of the PMTub gene has been observed in the wild-type bacilli when infecting macrophages, our results strongly suggest that the Mtb mannoproteome may undergo adaptive regulation during infection of the host cells. Overall, our results provide deeper insights into the complexity of the repertoire of mannosylated proteins expressed by Mtb, and open the way to novel opportunities to search for still-unexploited potential therapeutic targets.
Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress
Authors: Cervantes-García Daniel , Bahena-Delgado Armida I. , Jiménez Mariela , Córdova-Dávalos Laura E. , Ruiz-Esparza Palacios Vanessa , Sánchez-Alemán Esperanza , Martínez-Saldaña María C. , Salinas Eva
Published: May 2020

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.
Mechanisms Regulating the UPS-ALS Crosstalk: The Role of Proteaphagy
Authors: Quinet Grégoire , Gonzalez-Santamarta Maria , Louche Clara , Rodriguez Manuel S.
Published: May 2020

Protein degradation is tightly regulated inside cells because of its utmost importance for protein homeostasis (proteostasis). The two major intracellular proteolytic pathways are the ubiquitin-proteasome and the autophagy-lysosome systems which ensure the fate of proteins when modified by various members of the ubiquitin family. These pathways are tightly interconnected by receptors and cofactors that recognize distinct chain architectures to connect with either the proteasome or autophagy under distinct physiologic and pathologic situations. The degradation of proteasome by autophagy, known as proteaphagy, plays an important role in this crosstalk since it favours the activity of autophagy in the absence of fully active proteasomes. Recently described in several biological models, proteaphagy appears to help the cell to survive when proteostasis is broken by the absence of nutrients or the excess of proteins accumulated under various stress conditions. Emerging evidence indicates that proteaphagy could be permanently activated in some types of cancer or when chemoresistance is observed in patients.
Sexual Dimorphism in Energy Metabolism of Wistar Rats Using Data Analysis
Authors: Leskanicova Andrea , Chovancova Olga , Babincak Marian , Verboova Ludmila , Benetinova Zuzana , Macekova Denisa , Kostolny Jozef , Smajda Benadik , Kiskova Terezia
Published: May 2020

The prevalence of some chronic diseases, such as cancer or neurodegenerative disorders, differs between sexes. Animal models provide an important tool to adopt potential therapies from preclinical studies to humans. Laboratory rats are the most popular animals in toxicology, neurobehavioral, or cancer research. Our study aimed to reveal the basic differences in blood metabolome (amino acids, biogenic amines, and acylcarnitines) of the adult male (n = 10) and female (n = 10) Wistar rats. Partial least square-discrimination analysis (PLS-DA) and a variance im portance in projection (VIP) score was used to identify the key sex-specific metabolites. All groups of metabolites, as the main markers of energy metabolism, showed a significant sex-dependent pattern. The most important features calculated in PLS-DA according to VIP score were free carnitine (C0), tyrosine (Tyr), and acylcarnitine C5-OH. While aromatic amino acids, such as Tyr and phenylalanine (Phe), were significantly elevated in the blood plasma of males, tryptophan (Trp) was found in higher levels in the blood plasma of females. Besides, significant sex-related changes in urea cycle were found. Our study provides an important insight into sex-specific differences in energy metabolism in rats and indicates that further studies should consider sex as the main aspect in design and data interpretation.
Synthesis and Cytotoxic Activity of Chiral Sulfonamides Based on the 2-Azabicycloalkane Skeleton
Authors: Samadaei Mahzeiar , Pinter Matthias , Senfter Daniel , Madlener Sibylle , Rohr-Udilova Nataliya , Iwan Dominika , Kamińska Karolina , Wojaczyńska Elżbieta , Wojaczyński Jacek , Kochel Andrzej
Published: May 2020

A series of chiral sulfonamides containing the 2-azabicycloalkane scaffold were prepared from aza-Diels–Alder cycloadducts through their conversion to amines based on 2-azanorbornane or the bridged azepane skeleton, followed by the reaction with sulfonyl chlorides. The cytotoxic activity of the obtained bicyclic derivatives was evaluated using human hepatocellular carcinoma (HCC), medulloblastoma (MB), and glioblastoma (GBM) cell lines. Chosen compounds were shown to notably reduce cell viability as compared to nonmalignant cells.
Transfer Learning: Making Retrosynthetic Predictions Based on a Small Chemical Reaction Dataset Scale to a New Level
Authors: Bai Renren , Zhang Chengyun , Wang Ling , Yao Chuansheng , Ge Jiamin , Duan Hongliang
Published: May 2020

Effective computational prediction of complex or novel molecule syntheses can greatly help organic and medicinal chemistry. Retrosynthetic analysis is a method employed by chemists to predict synthetic routes to target compounds. The target compounds are incrementally converted into simpler compounds until the starting compounds are commercially available. However, predictions based on small chemical datasets often result in low accuracy due to an insufficient number of samples. To address this limitation, we introduced transfer learning to retrosynthetic analysis. Transfer learning is a machine learning approach that trains a model on one task and then applies the model to a related but different task; this approach can be used to solve the limitation of few data. The unclassified USPTO-380K large dataset was first applied to models for pretraining so that they gain a basic theoretical knowledge of chemistry, such as the chirality of compounds, reaction types and the SMILES form of chemical structure of compounds. The USPTO-380K and the USPTO-50K (which was also used by Liu et al.) were originally derived from Lowe’s patent mining work. Liu et al. further processed these data and divided the reaction examples into 10 categories, but we did not. Subsequently, the acquired skills were transferred to be used on the classified USPTO-50K small dataset for continuous training and retrosynthetic reaction tests, and the pretrained accuracy data were simultaneously compared with the accuracy of results from models without pretraining. The transfer learning concept was combined with the sequence-to-sequence (seq2seq) or Transformer model for prediction and verification. The seq2seq and Transformer models, both of which are based on an encoder-decoder architecture, were originally constructed for language translation missions. The two algorithms translate SMILES form of structures of reactants to SMILES form of products, also taking into account other relevant chemical information (chirality, reaction types and conditions). The results demonstrated that the accuracy of the retrosynthetic analysis by the seq2seq and Transformer models after pretraining was significantly improved. The top-1 accuracy (which is the accuracy rate of the first prediction matching the actual result) of the Transformer-transfer-learning model increased from 52.4% to 60.7% with greatly improved prediction power. The model’s top-20 prediction accuracy (which is the accuracy rate of the top 20 categories containing actual results) was 88.9%, which represents fairly good prediction in retrosynthetic analysis. In summary, this study proves that transferring learning between models working with different chemical datasets is feasible. The introduction of transfer learning to a model significantly improved prediction accuracy and, especially, assisted in small dataset based reaction prediction and retrosynthetic analysis.
Chemical, Bioactivity, and Biosynthetic Screening of Epiphytic Fungus Zasmidium pseudotsugae
Authors: González-Montiel Gisela A. , Kaweesa Elizabeth N. , Feau Nicolas , Hamelin Richard C. , Stone Jeffrey K. , Loesgen Sandra
Published: May 2020

We report the first secondary metabolite, 8,8′-bijuglone, obtained from pure cultures of the slow growing Douglas fir- (Pseudotsuga menziesii var. menziesii) foliage-associated fungus Zasmidium pseudotsugae. The quinone was characterized using extensive LC/MS and NMR-based spectroscopic methods. 8,8′-Bijuglone exhibited moderate antibiotic activity against Gram-positive pathogens and weak cytotoxic activity in the NCI-60 cell line panel and in our in-house human colon carcinoma (HCT-116) cell line. An analysis of the fungal genome sequence to assess its metabolic potential was implemented using the bioinformatic tool antiSMASH. In total, 36 putative biosynthetic gene clusters were found with a majority encoding for polyketides (17), followed by non-ribosomal peptides (14), terpenes (2), ribosomal peptides (1), and compounds with mixed biosynthetic origin (2). This study demonstrates that foliage associated fungi of conifers produce antimicrobial metabolites and suggests this guild of fungi may present a rich source of novel molecules.
Alkalinity and Its Consequences for the Performance of Steel-Reinforced Geopolymer Materials
Authors: Koenig Andreas , Mahmoud Hitham , Baehre Oliver , Dehn Frank
Published: May 2020

This paper investigates the development of the alkalinity and its impact on carbon steel reinforcement embedded in alkali-activated fly ashes (AAFA) and alkali-activated fly ashes with ten percentage mass (wt%) of blast furnace slag (AAFAS)-based materials (geopolymer–GP). The pH analysis of eluates indicates a remarkable decrease of alkalinity in AAFA and AAFAS in the first hours of the geopolymerization process. Phenolphthalein solution and pore solution tests on concretes also show a sharp decrease of alkalinity with increased Ca content in the binder due to carbonation. Micro X-ray computer tomography (µXCT) and electrochemical techniques indicate that the changed pH in the GP systems was accompanied by a decrease in the corrosion rates of steel reinforcement when compared to ordinary Portland cement (OPC) systems. In contrast to calcite and vaterite, which were detected in OPC and AAFAS after a carbonation process, only sodium carbonate natron was determined at lower levels in AAFA by X-ray diffraction (XRD).
Leading Interaction Components in the Structure and Reactivity of Noble Gases Compounds
Authors: Nunzi Francesca , Pannacci Giacomo , Tarantelli Francesco , Belpassi Leonardo , Cappelletti David , Falcinelli Stefano , Pirani Fernando
Published: May 2020

The nature, strength, range and role of the bonds in adducts of noble gas atoms with both neutral and ionic partners have been investigated by exploiting a fine-tuned integrated phenomenological–theoretical approach. The identification of the leading interaction components in the noble gases adducts and their modeling allows the encompassing of the transitions from pure noncovalent to covalent bound aggregates and to rationalize the anomalous behavior (deviations from noncovalent type interaction) pointed out in peculiar cases. Selected adducts affected by a weak chemical bond, as those promoting the formation of the intermolecular halogen bond, are also properly rationalized. The behavior of noble gas atoms excited in their long-life metastable states, showing a strongly enhanced reactivity, has been also enclosed in the present investigation.
Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5
Authors: Trammell Samuel A. J. , Svenningsen Jens S. , Holst Jens J. , Gillum Matthew P. , Kuhre Rune E.
Published: May 2020

Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are the two known bile acid (BA) sensitive receptors and are expressed in the intestine and liver as well as in extra-enterohepatic tissues. The physiological effects of extra-enterohepatic FXR/TRG5 remain unclear. Further, the extent BAs escape liver reabsorption and how they interact with extra-enterohepatic FXR/TGR5 is understudied. We investigated if hepatic BA reuptake differed between BAs agonistic for FXR and TGR5 compared to non-agonists in the rat. Blood was collected from the portal vein and inferior caval vein from anesthetized rats before and 5, 20, 30, and 40 min post stimulation with sulfated cholecystokinin-8. Plasma concentrations of 20 different BAs were assessed by liquid chromatography coupled to mass spectrometry. Total portal vein BA AUC was 3–4 times greater than in the vena cava inferior (2.7 ± 0.6 vs. 0.7 ± 0.2 mM x min, p < 0.01, n = 8) with total unconjugated BAs being 2–3-fold higher than total conjugated BAs (AUC 8–10 higher p < 0.05 for both). However, in both cases, absolute ratios varied greatly among different BAs. The average hepatic reuptake of BAs agonistic for FXR/TGR5 was similar to non-agonists. However, as the sum of non-agonist BAs in vena portae was 2–3-fold higher than the sum agonist (p < 0.05), the peripheral BA pool was composed mostly of non-agonist BAs. We conclude that hepatic BA reuptake varies substantially by type and does not favor FXR/TGR5 BAs agonists.
Anti-Inflammatory and Cytotoxic Potential of New Phenanthrenoids from Luzula sylvatica
Authors: Gainche Maël , Ripoche Isabelle , Senejoux François , Cholet Juliette , Ogeron Clémence , Decombat Caroline , Danton Ombeline , Delort Laetitia , Vareille-Delarbre Marjolaine , Berry Alexandre , Vermerie Marion , Fraisse Didier , Felgines Catherine , Ranouille Edwige , Berthon Jean-Yves , Priam Julien , Saunier Etienne , Tourrette Albert , Troin Yves , Caldefie-Chezet Florence , Chalard Pierre
Published: May 2020

Phenanthrenoids have been widely described, in the Juncaceae family, for their biological properties such as antitumor, anxiolytic, anti-microbial, spasmolytic, and anti-inflammatory activities. The Juncaceae family is known to contain a large variety of phenanthrenoids possessing especially anti-inflammatory and cytotoxic properties. Luzula sylvatica, a Juncaceae species, is widely present in the Auvergne region of France, but has never been studied neither for its phytochemical profile nor for its biological properties. We investigated the phytochemical profile and evaluated the potential anti-inflammatory activities of L. sylvatica aerial parts extracts. A bioassay-guided fractionation was carried out to identify the most active fractions. Nine compounds were isolated, one coumarin 1 and eight phenanthrene derivatives (2–9), including four new compounds (4, 5, 8 and 9), from n-hexane and CH2Cl2, fractions. Their structures were established by HRESIMS, 1D and 2D NMR experiments. The biological properties, especially the anti-inflammatory/antioxidant activities (ROS production) and antiproliferative activity on THP-1, a monocytic leukemia cell line, of each compound, were evaluated. Three phenanthrene derivatives 4, 6, and 7 showed very promising antiproliferative activities.
Extent and Variation of Nitrogen Losses from Non-legume Field Crops of Conterminous United States
Authors: Chatterjee Amitava
Published: May 2020

Nitrogen (N) losses from field crops have raised environmental concerns. This manuscript accompanies a database of N loss studies from non-legume field crops conducted across the conterminous United States. Cumulative N losses through nitrous oxide-denitrification (CN2O), ammonia volatilization (CNH3), and nitrate leaching (CNO3−) during the growing season and associated crop, soil, and water management information were gathered to determine the extent and controls of these losses. This database consisted of 404, 26, and 358 observations of CN2O, CNH3, and CNO3− losses, respectively, from sixty-two peer-reviewed manuscripts. Corn (Zea mays) dominated the N loss studies. Losses ranged between −0.04 to 16.9, 2.50 to 50.9, and 0 to 257 kg N ha−1 for CN2O, CNH3 and CNO3−, respectively. Most CN2O and CNO3− observations were reported from Colorado (n = 100) and Iowa (n = 176), respectively. The highest values of CN2O, and CNO3− were reported from Illinois and Minnesota states, and corn and potato (Solanum tuberosum), respectively. The application of anhydrous NH3 had the highest value of CN2O loss, and ammonium nitrate had the highest CNO3− loss. Among the different placement methods, the injection of fertilizer-N had the highest CN2O loss, whereas the banding of fertilizer-N had the highest CNO3− loss. The maximum CNO3− loss was higher for chisel than no-tillage practice. Both CN2O and CNO3− were positively correlated with fertilizer N application rate and the amount of water input (irrigation and rainfall). Fertilizer-N management strategies to control N loss should consider the spatio-temporal variability of interactions among climate, crop-and soil types.
COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation
Authors: Zabetakis Ioannis , Lordan Ronan , Norton Catherine , Tsoupras Alexandros
Published: May 2020

The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted “stay in place” or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.
Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased Lactobacillus Abundance in the Human Gut Microbiome
Authors: Butler Mary I. , Bastiaanssen Thomaz F. S. , Long-Smith Caitriona , Berding Kirsten , Morkl Sabrina , Cusack Anne-Marie , Strain Conall , Busca Kizkitza , Porteous-Allen Penny , Claesson Marcus J. , Stanton Catherine , Cryan John F. , Allen Darina , Dinan Timothy G.
Published: May 2020

Introduction: The gut microbiota plays a role in gut–brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm. Methods: Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured. Results: Relative abundance of the genus Lactobacillus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut–brain module approach. Conclusions: While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, Lactobacillus, in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as Lactobacillus, which are recognised as being beneficial for a range of physical and mental health outcomes.
Effect of Supplementation with Saccharomyces Boulardii on Academic Examination Performance and Related Stress in Healthy Medical Students: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Karbownik Michał Seweryn , Kręczyńska Joanna , Kwarta Paulina , Cybula Magdalena , Wiktorowska-Owczarek Anna , Kowalczyk Edward , Pietras Tadeusz , Szemraj Janusz
Published: May 2020

In recent years, bacterial probiotic dietary supplementation has emerged as a promising way to improve cognition and to alleviate stress and anxiety; however, yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii enhances academic performance under stress and affects stress markers. The trial was retrospectively registered at clinicaltrials.gov (NCT03427515). Healthy medical students were randomized to supplement their diet with Saccharomyces boulardii CNCM I-1079 or placebo before sitting for an academic examination, which served as a model of stress. The grades of a final examination adjusted to subject knowledge tested in non-stressful conditions was used as a primary outcome measure. Psychometrically evaluated state anxiety, cortisol and metanephrine salivary levels, and pulse rate were tested at a non-stressful time point before the intervention as well as just before the stressor. Fifty enrolled participants (22.6 ± 1.4 years of age, 19 males) completed the trial in the Saccharomyces and placebo arms. Supplementation with Saccharomyces did not significantly modify examination performance or increase in state anxiety, salivary cortisol, and metanephrine. However, the intervention resulted in higher increase in pulse rate under stress as compared to placebo by 10.4 (95% CI 4.2–16.6) min−1 (p = 0.0018), and the effect positively correlated with increase in salivary metanephrine (Pearson’s r = 0.35, 95% CI 0.09–0.58, p = 0.012). An intention-to-treat analysis was in line with the per-protocol one. In conclusion, supplementation with Saccharomyces boulardii CNCM I-1079 appears largely ineffective in improving academic performance under stress and in alleviating some stress markers, but it seems to increase pulse rate under stress, which may hypothetically reflect enhanced sympathoadrenal activity.
Dietary Supplements for Male Infertility: A Critical Evaluation of Their Composition
Authors: Garolla Andrea , Petre Gabriel Cosmin , Francini-Pesenti Francesco , De Toni Luca , Vitagliano Amerigo , Di Nisio Andrea , Foresta Carlo
Published: May 2020

Dietary supplements (DS) represent a possible approach to improve sperm parameters and male fertility. A wide range of DS containing different nutrients is now available. Although many authors demonstrated benefits from some nutrients in the improvement of sperm parameters, their real effectiveness is still under debate. The aim of this study was to critically review the composition of DS using the Italian market as a sample. Active ingredients and their minimal effective daily dose (mED) on sperm parameters were identified through a literature search. Thereafter, we created a formula to classify the expected efficacy of each DS. Considering active ingredients, their concentration and the recommended daily dose, DS were scored into three classes of expected efficacy: higher, lower and none. Twenty-one DS were identified. Most of them had a large number of ingredients, frequently at doses below mED or with undemonstrated efficacy. Zinc was the most common ingredient of DS (70% of products), followed by selenium, arginine, coenzyme Q and folic acid. By applying our scoring system, 9.5% of DS fell in a higher class, 71.4% in a lower class and 19.1% in the class with no expected efficacy. DS marketed in Italy for male infertility frequently includes effective ingredients but also a large number of substances at insufficient doses or with no reported efficacy. Manufacturers and physicians should better consider the scientific evidence on effective ingredients and their doses before formulating and prescribing these products.
Commiphora Extract Mixture Ameliorates Monosodium Iodoacetate-Induced Osteoarthritis
Authors: Lee Donghun , Ju Mi-Kyoung , Kim Hocheol
Published: May 2020

Osteoarthritis (OA) is a chronic inflammatory joint disease that affects millions of elderly people around the world. The conventional treatments for OA consisting of nonsteroidal anti-inflammatory drugs and steroid have negative health consequences, such as gastrointestinal, renal, and cardiac diseases. This study has evaluated the Commiphora extract mixture (HT083) on OA progression as an alternative treatment in animal models. The root of P. lactiflora and the gum resin of C. myrrha have been in use as traditional medicines against many health problems including bone disorders since ancient time. The extracts of P. lactiflora root and C. myrrha gum resin were mixed as 3:1 for their optimal effects. Male Sprague-Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce the symptoms identical to human OA. HT083 substantially prevented the loss of weight-bearing inflicted with MIA in rats. The MIA-induced cartilage erosion as well as the subchondral bone damage in the rats was also reversed. In addition, the increase of serum IL-1β concentration, a crucial pro-inflammatory cytokine involved in OA progression was countered by HT083. Furthermore, HT083 significantly reduced the acetic acid-induced writhing response in mice. In vitro, HT083 has shown potent anti-inflammatory activities by inhibiting the production of NO and suppressing the interleukin -1β, interleukin -6, cyclooxygenase-2, and inducible nitric oxide synthase expression in lipopolysaccharide -stimulated RAW 264.7 cells. Given its potent analgesic and anti-inflammatory activities in MIA rats and acetic acid-induced writhing in mice, HT083 should be further studied in order to explain its mechanism of actions in alleviating OA pain and inflammation.
Association between Obesity and Omega-3 Status in Healthy Young Women
Authors: Young Isabel E. , Parker Helen M. , Cook Rebecca L. , O’Dwyer Nicholas J. , Garg Manohar L. , Steinbeck Kate S. , Cheng Hoi Lun , Donges Cheyne , Franklin Janet L. , O’Connor Helen T.
Published: May 2020

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for healthy development and protect against metabolic disease. However, individuals with obesity may be pre-disposed to experiencing lower n-3 PUFA status than normal-weight individuals. This cross-sectional study examined the relationship between the omega-3 index (O3I), body mass index (BMI) and dietary intake in healthy young women (n = 300; age = 18–35 y), a group not previously focused on. Intake was adjusted for energy using the residuals method, and associations were explored using independent t-tests and Pearson’s correlations. Participants with obesity were found to have significantly lower O3I than normal-weight participants (p < 0.0001); however, no significant differences were observed in mean n-3 PUFA intakes. Even so, energy-adjusted intakes of n-3 PUFAs, with the exception of alpha-linolenic acid, were significantly correlated with O3I. This study demonstrates that O3I is influenced by both BMI and diet in young women; however the relationship between these two variables may be complex. Current intakes of n-3 PUFA observed in young women may not be effective in achieving target O3I levels in those with obesity, and further research is needed to find effective ways of improving n-3 PUFA status in a group already at increased risk of metabolic disease.