bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Polymeric and Biocompatible Delivery Systems by Dissolving Mesoporous Silica Templates
Authors: Rodríguez-Ramos Ana , Marín-Caba Laura , Iturrioz-Rodríguez Nerea , Padín-González Esperanza , García-Hevia Lorena , Mêna Oliveira Teresa , Corea-Duarte Miguel A. , Fanarraga Mónica L.
Published: December 2020

There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.
Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb Upregulation
Authors: Lee Yoo-Jin , Kim Jongsun
Published: December 2020

Natural killer (NK) cells are suitable targets for cancer immunotherapy owing to their potent cytotoxic activity. To maximize the therapeutic efficacy of cancer immunotherapy, adjuvants need to be identified. Resveratrol is a well-studied polyphenol with various potential health benefits, including antitumor effects. We previously found that resveratrol is an NK cell booster, suggesting that it can serve as an adjuvant for cancer immunotherapy. However, the molecular mechanism underlying the activation of NK cells by resveratrol remains unclear. The present study aimed to determine this mechanism. To this end, we investigated relevant pathways in NK cells using Western blot, real-time polymerase chain reaction, pathway inhibitor, protein/DNA array, and cytotoxicity analyses. We confirmed the synergistic effects of resveratrol and interleukin (IL)-2 on enhancing the cytolytic activity of NK cells. Resveratrol activated Akt by regulating Mammalian Target of Rapamycin (mTOR) Complex 2 (mTORC2) via phosphatase and tensin homolog (PTEN) and ribosomal protein S6 kinase beta-1 (S6K1). Moreover, resveratrol-mediated NK cell activation was more dependent on the mTOR pathway than the Akt pathway. Importantly, resveratrol increased the expression of c-Myb, a downstream transcription factor of Akt and mTORC2. Moreover, c-Myb was essential for resveratrol-induced NK cell activation in combination with IL-2. Our results demonstrate that resveratrol activates NK cells through Akt- and mTORC2-mediated c-Myb upregulation.
Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor
Authors: Park Kyung-Ran , Kim SooHyun , Cho MyoungLae , Kang Sang Wook , Yun Hyung-Mun
Published: December 2020

Styrax Japonica Sieb. et Zucc. has been used as traditional medicine in inflammatory diseases, and isolated compounds have shown pharmacological activities. Pinoresinol glucoside (PIN) belonging to lignins was isolated from the stem bark of S. Japonica. This study aimed to investigate the biological function and mechanisms of PIN on cell migration, osteoblast differentiation, and matrix mineralization. Herein, we investigated the effects of PIN in MC3T3-E1 pre-osteoblasts, which are widely used for studying osteoblast behavior in in vitro cell systems. At concentrations ranging from 0.1 to 100 μM, PIN had no cell toxicity in pre-osteoblasts. Pre-osteoblasts induced osteoblast differentiation, and the treatment of PIN (10 and 30 μM) promoted the cell migration rate in a dose-dependent manner. At concentrations of 10 and 30 μM, PIN elevated early osteoblast differentiation in a dose-dependent manner, as indicated by increases in alkaline phosphatase (ALP) staining and activity. Subsequently, PIN also increased the formation of mineralized nodules in a dose-dependent manner, as indicated by alizarin red S (ARS) staining, demonstrating positive effects of PIN on late osteoblast differentiation. In addition, PIN induced the mRNA level of BMP2, ALP, and osteocalcin (OCN). PIN also upregulated the protein level of BMP2 and increased canonical BMP2 signaling molecules, the phosphorylation of Smad1/5/8, and the protein level of Runt-related transcription factor 2 (RUNX2). Furthermore, PIN activated non-canonical BMP2 signaling molecules, activated MAP kinases, and increased β-catenin signaling. The findings of this study indicate that PIN has biological roles in osteoblast differentiation and matrix mineralization, and suggest that PIN might have anabolic effects in bone diseases such as osteoporosis and periodontitis.
Progress in the Preparation of Functional and (Bio)Degradable Polymers via Living Polymerizations
Authors: Lin Si-Ting , Wang Chung-Chi , Chang Chi-Jung , Nakamura Yasuyuki , Lin Kun-Yi Andrew , Huang Chih-Feng
Published: December 2020

This review presents the latest developments in (bio)degradable approaches and functional aliphatic polyesters and polycarbonates prepared by typical ring-opening polymerization (ROP) of lactones and trimethylene carbonates. It also considers several recent innovative synthetic methods including radical ring-opening polymerization (RROP), atom transfer radical polyaddition (ATRPA), and simultaneous chain- and step-growth radical polymerization (SCSRP) that produce aliphatic polyesters. With regard to (bio)degradable approaches, we have summarized several representative cleavable linkages that make it possible to obtain cleavable polymers. In the section on functional aliphatic polyesters, we explore the syntheses of specific functional lactones, which can be performed by ring-opening copolymerization of typical lactone/lactide monomers. Last but not the least, in the recent innovative methods section, three interesting synthetic methodologies, RROP, ATRPA, and SCSRP are discussed in detail with regard to their reaction mechanisms and polymer functionalities.
ER–Mitochondria Contacts and Insulin Resistance Modulation through Exercise Intervention
Authors: Sun Yi , Ding Shuzhe
Published: December 2020

The endoplasmic reticulum (ER) makes physical contacts with mitochondria at specific sites, and the hubs between the two organelles are called mitochondria-associated ER membranes (MAMs). MAMs are known to play key roles in biological processes, such as intracellular Ca2+ regulation, lipid trafficking, and metabolism, as well as cell death, etc. Studies demonstrated that dysregulation of MAMs significantly contributed to insulin resistance. Alterations of MAMs’ juxtaposition and integrity, impaired expressions of insulin signaling molecules, disruption of Ca2+ homeostasis, and compromised metabolic flexibility are all actively involved in the above processes. In addition, exercise training is considered as an effective stimulus to ameliorate insulin resistance. Although the underlying mechanisms for exercise-induced improvement in insulin resistance are not fully understood, MAMs may be critical for the beneficial effects of exercise.
Investigation of Risk Factors for Pain Chronification in Patients Suffering from Infections of the Spine
Authors: Zhao Yina , Hemmer Stefan , Pepke Wojciech , Akbar Michael , Schiltenwolf Marcus , Dapunt Ulrike
Published: December 2020

Background: Spinal infections represent a therapeutic challenge. The often protracted course of the disease is accompanied by pain, which can lead to a chronic pain experience even after the infectious disease has been treated successfully. The aim of this study was to investigate possible risk factors of pain chronification. Methods: In a prospective study, 14 patients with spinal infections were examined at admission (T1), at discharge from inpatient therapy (T2), and three to eight months postoperatively (T3) byquestionnaires on risk factors for pain chronification and by quantitative sensory testing (QST). Results: In-patient treatment lasted on average 45.3 days (±33.13). The patients complained of pain for 3.43 months (±2.77) prior to inpatient treatment. The visual analogue scale (VAS) for pain (0–10) and the Oswestry Disability Index detected significant improvement in the course of the study. However, patients also reported catastrophic thinking, as well as fear of movement and (re)-injury. Conclusion: In summary, our results demonstrate that patients with spinal infections did not suffer from pain chronification, but might benefit from an interdisciplinary therapeutic approach, which emphasizes promoting active pain-coping strategies, as well as addressing fear of movement and catastrophic thinking.
Clinical Evaluation of a Newly Developed Guidewire for Pancreatobiliary Endoscopy
Authors: Ishii Shigeto , Fujisawa Toshio , Isayama Hiroyuki , Asahara Shingo , Ogiwara Shingo , Okubo Hironao , Yamagata Hisafumi , Ushio Mako , Takahashi Sho , Okawa Hiroki , Yamagata Wataru , Okawa Yoshihiro , Suzuki Akinori , Takasaki Yusuke , Ochiai Kazushige , Tomishima Ko , Saito Hiroaki , Shiina Shuichiro , Ikari Takaaki
Published: December 2020

Background: The guidewire (GW) plays an important role in pancreatobiliary endoscopy. GW quality is a critical factor in the effectiveness and efficiency of pancreatobiliary endoscopy. In this study, we evaluate a new 0.025 inch multipurpose endoscopic GW: the M-Through. Methods: Our study was a multicenter retrospective analysis. We enrolled patients who underwent endoscopic procedures using the M-Through between May 2018 and April 2020. Patients receiving the following endoscopic treatments were enrolled: common bile duct (CBD) stone extraction, endoscopic drainage for distal and hilar malignant biliary obstruction (MBO), and endoscopic drainage for acute cholecystitis. For each procedure, we examined the rate of success without GW exchange. Results: A total of 170 patients (80 with CBD stones, 60 with MBO, and 30 with cholecystitis) were enrolled. The rate of completion without GW exchange was 100% for CBD stone extraction, 83.3% for endoscopic drainage for MBO, and 43.3% for endoscopic drainage for cholecystitis. In unsuccessful cholecystitis cases with the original GW manipulator, 1 of 8 cases succeeded in the manipulator exchange. Including 6 cases who changed GW after the manipulator exchange, 11 of 16 cases succeeded in changing GW. There was significant difference in the success rate between the manipulator exchange and GW exchange (p = 0.03). The insertion of devices and stent placement after biliary cannulation (regardless of type) were almost completed with M-through. We observed no intraoperative GW-related adverse events such as perforation and bleeding due to manipulation. Conclusion: The 0.025 inch M-Through can be used for endoscopic retrograde cholangiopancreatography-related procedures efficiently and safely. Our study found high rates of success without GW exchange in all procedures except for endoscopic drainage for cholecystitis. This GW is considered (1) excellent for supportability of device insertion to remove CBD stones; (2) good for seeking the biliary malignant stricture but sometimes need the help of a hydrophilic GW; (3) suboptimal for gallbladder drainage that require a high level of seeking ability.
Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals
Authors: Tu Cheng-Hao , Chen Chun-Ming , Yang Chuan-Chih , Gałecki Piotr , Su Kuan-Pin
Published: December 2020

N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical compounds, we recruited 24 MDD subjects in this double-blind, head-to-head study with a 12-week EPA or DHA treatment (clinical trial registration number: NCT03871088). The depression severity was assessed by Hamilton depression rating scale (HAM-D). Brain responses to emotional stimuli were measured by a 3-Tesla MRI. The correlation between HAM-D scores and brain responses also were tested. Compared to 18 healthy controls, the brain responses of untreated 24 MDD patients mainly revealed hypoactivity in the regions associated with emotion perception and emotion control when processing positive emotion. After treatment, more remitted MDD patients have been observed in the EPA as compared to the DHA groups. In addition, the EPA, but not DHA, treatment revealed increased activity in the regions associated with emotion perception and cognitive control when processing positive emotion. The correlation analysis further revealed negative correlation between HAM-D scores and brain responses in cognitive control regions. The results of this study may imply the compensatory brain responses of cognitive and emotion controls by EPA but not DHA and underpin personalized medicine with anti-inflammatory nutraceuticals toward depression treatments.
Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review
Authors: Vinnikov Volodymyr , Hande Manoor Prakash , Wilkins Ruth , Wojcik Andrzej , Zubizarreta Eduardo , Belyakov Oleg
Published: December 2020

A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4–6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts.
Neural Network-Based Automated Assessment of Fatigue Damage in Mechanical Structures
Authors: Alqahtani Hassan , Ray Asok
Published: December 2020

This paper proposes a methodology for automated assessment of fatigue damage, which has been tested and validated with polycrystalline-alloy (Aℓ7075-T6) specimens on an experimental apparatus. Based on an ensemble of time series of ultrasonic test (UT) data, the proposed procedure is found to be capable of detecting fatigue-damage (at an early stage) in mechanical structures, which is followed by online evaluation of the associated risk. The underlying concept is built upon two neural network (NN)-based models, where the first NN model identifies the feature of the UT data belonging to one of the two classes: undamaged structure and damaged structure, and the second NN model further classifies an identified damaged structure into three classes: low-risk, medium-risk, and high-risk. The input information to the second NN model is the crack tip opening displacement (CTOD), which is computed by the first NN model via linear regression from an ensemble of optical data, acquired from the experiments. Both NN models have been trained by using scaled conjugate gradient algorithms. The results show that the first NN model classifies the energy of UT signals with (up to) 98.5% accuracy, and that the accuracy of the second NN model is 94.6%.
Plasma-Assisted Chemical Vapor Deposition of TiBN Coatings on Nanostructured Cemented WC-Co
Authors: Sakoman Matija , Ćorić Danko , Šnajdar Musa Mateja
Published: December 2020

The plasma-assisted chemical vapor deposition (PACVD) technique has shown many advantages in applications, where thin coatings with superior wear properties are demanded, especially for geometrically complex parts. In this study, multilayered gradient TiBN coatings that were deposited on nanostructured cemented carbides by the PACVD method were investigated. Nanostructured samples of cemented carbides with the addition of 5 and 15 wt.% Co were sintered by the hot isostatic pressing, sinter-HIP technique. Surface preparation was conducted on samples in order to enable maximum coating adhesion. Tests that were conducted on produced samples aimed to investigate the mechanical and physical properties of coated samples. These tests included nanoindentation, surface layer characterization, and coating adhesion evaluation while using the Rockwell and scratch test. The obtained results confirmed that the PACVD process can be utilized for applying thin hard coatings to nanostructured cemented carbides that are produced by the sinter HIP process, resulting in a base material/ coating system that exhibits excellent physical and mechanical properties. The results presented in this paper give a valuable contribution to the research of TiBN coating systems and their potential for application under heavy wear conditions.
Dislocation Breakaway Damping in AA7050 Alloy
Authors: Schino Andrea Di , Montanari Roberto , Testani Claudio , Varone Alessandra
Published: December 2020

The AA7050 alloy prepared through the standard industrial hot-forging cycle has been investigated by means of isothermal mechanical spectroscopy (MS) from room temperature up to 185 °C. Each MS test consisted of a cycle with two stages, at increasing and decreasing strain. After each cycle the damping value resulted to be higher than the original one indicating the occurrence of an irreversible transformation. Such phenomenon, observed for all the test temperatures, becomes more relevant for T ≥ 150 °C. The irreversible transformation has been discussed and explained by considering the evolution of the mean dislocation link length between pinning points represented by nanometric MgZn2 precipitates. The breakaway of dislocation segments from pinning points occurs in the stage at increasing strain and is not fully recovered during the second stage at decreasing strain thus the mean link length increases in a MS test cycle. The onset of thermal activated dislocation cross-slip at about 150 °C favors the dislocation breakaway and consequently enhances the effect on damping.
Electrowetting-on-Dielectric Based Economical Digital Microfluidic Chip on Flexible Substrate by Inkjet Printing
Authors: Wang He , Chen Liguo
Published: December 2020

In order to get rid of the dependence on expensive photolithography technology and related facilities, an economic and simple design and fabrication technology for digital microfluidics (DMF) is proposed. The electrodes pattern was generated by inkjet printing nanosilver conductive ink on the flexible Polyethylene terephthalate (PET) substrate with a 3D circuit board printer, food wrap film was attached to the electrode array to act as the dielectric layer and Teflon® AF was sprayed to form a hydrophobic layer. The PET substrate and food wrap film are low cost and accessible to general users. The proposed flexible DMF chips can be reused for a long time by replacing the dielectric film coated with hydrophobic layer. The resolution and conductivity of silver traces and the contact angle and velocity of the droplets were evaluated to demonstrate that the proposed technology is comparable to the traditional DMF fabrication process. As far as the rapid prototyping of DMF is concerned, this technology has shown very attractive advantages in many aspects, such as fabrication cost, fabrication time, material selection and mass production capacity, without sacrificing the performance of DMF. The flexible DMF chips have successfully implemented basic droplet operations on a square and hexagon electrode array.
Identification of a Candidate Starch Utilizing Strain of Prevotella albensis from Bovine Rumen
Authors: Bandarupalli Venkata Vinay Kumar , St-Pierre Benoit
Published: December 2020

The inclusion of starch-rich feedstuffs, a common practice in intensive ruminant livestock production systems, can result in ruminal acidosis, a condition that can severely impact animal performance and health. One of the main causes of acidosis is the rapid accumulation of ruminal short chain fatty acids (SCFAs) resulting from the microbial digestion of starch. A greater understanding of ruminal bacterial amylolytic activities is therefore critical to improving mitigation of acidosis. To this end, our manuscript reports the identification of a candidate starch utilizer (OTU SD_Bt-00010) using batch culturing of bovine rumen fluid supplemented with starch. Based on 16S rRNA gene sequencing and metagenomics analysis, SD_Bt-00010 is predicted to be a currently uncharacterized strain of Prevotella albensis. Annotation of de novo assembled contigs from metagenomic data not only identified sequences encoding for α-amylase enzymes, but also revealed the potential to metabolize xylan as an alternative substrate. Metagenomics also predicted that SCFA end products for SD_Bt-00010 would be acetate and formate, and further suggested that this candidate strain may be a lactate utilizer. Together, these results indicate that SD_Bt-00010 is an amylolytic symbiont with beneficial attributes for its ruminant host.
The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?
Authors: Łusiak-Szelachowska Marzanna , Weber-Dąbrowska Beata , Żaczek Maciej , Borysowski Jan , Górski Andrzej
Published: December 2020

The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.
Experimental Study on the Link between Optical Emission, Crystal Defects and Photocatalytic Activity of Artist Pigments Based on Zinc Oxide
Authors: Artesani Alessia , Dozzi Maria Vittoria , Toniolo Lucia , Valentini Gianluca , Comelli Daniela
Published: December 2020

The historical knowledge inherited from house paint documents and the experimental research on synthetic pigments show that production methods have an important role in the performance of paint. In this regard, this work investigates the links existing between the optical emission, crystal defects and photocatalytic activity of zinc white pigment from different contemporary factories, with the aim of elucidating the effects of these characteristics onto the tendency of the pigment to induce paint failures. The analysed samples display highly similar crystallite structure, domain size, and specific surface area, whilst white pigments differ from pure ZnO in regards to the presence of zinc carbonate hydrate that is found as a foreign compound. In contrast, the photoluminescence measurements categorize the analysed samples into two groups, which display different trap-assisted emissions ascribed to point crystal defects introduced during the synthesis process, and associated to Zn or O displacement. The photocatalytic degradation tests infer that the emerged defective structure and specific surface area of ZnO-based samples influence their tendency to oxidize organic molecules under light irradiation. In particular, the results indicate that the zinc interstitial defects may be able to promote the photogenerated electron-hole couples separation with a consequent increase of the overall ZnO photocatalytic activity, negatively affecting the binding medium stability. This groundwork paves the way for further studies on the link between the photoluminescence emission of the zinc white pigment and its tendency to decompose organic components contained in the binding medium.
Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms
Authors: De Zoysa Gayan Heruka , Wang Kelvin , Lu Jun , Hemar Yacine , Sarojini Vijayalekshmi
Published: December 2020

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.
Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments
Authors: Mustière Romain , Vanelle Patrice , Primas Nicolas
Published: December 2020

Recent progress in reducing malaria cases and ensuing deaths is threatened by factors like mutations that induce resistance to artemisinin derivatives. Multiple drugs are currently in clinical trials for malaria treatment, including some with novel mechanisms of action. One of these, MMV390048, is a plasmodial kinase inhibitor. This review lists the recently developed molecules which target plasmodial kinases. A systematic review of the literature was performed using CAPLUS and MEDLINE databases from 2005 to 2020. It covers a total of 60 articles and describes about one hundred compounds targeting 22 plasmodial kinases. This work highlights the strong potential of compounds targeting plasmodial kinases for future drug therapies. However, the majority of the Plasmodium kinome remains to be explored.
Food Addiction and Tobacco Use Disorder: Common Liability and Shared Mechanisms
Authors: Zawertailo Laurie , Attwells Sophia , deRuiter Wayne K. , Le Thao Lan , Dawson Danielle , Selby Peter
Published: December 2020

As food addiction is being more commonly recognized within the scientific community, parallels can be drawn between it and other addictive substance use disorders, including tobacco use disorder. Given that both unhealthy diets and smoking are leading risk factors for disability and death, a greater understanding of how food addiction and tobacco use disorder overlap with one another is necessary. This narrative review aimed to highlight literature that investigated prevalence, biology, psychology, and treatment options of food addiction and tobacco use disorder. Published studies up to August 2020 and written in English were included. Using a biopsychosocial lens, each disorder was assessed together and separately, as there is emerging evidence that the two disorders can develop concurrently or sequentially within individuals. Commonalities include but are not limited to the dopaminergic neurocircuitry, gut microbiota, childhood adversity, and attachment insecurity. In addition, the authors conducted a feasibility study with the purpose of examining the association between food addiction symptoms and tobacco use disorder among individuals seeking tobacco use disorder treatment. To inform future treatment approaches, more research is necessary to identify and understand the overlap between the two disorders.
The Relationship of Dietary Pattern and Genetic Risk Score with the Incidence of Dyslipidemia: 14-Year Follow-Up Cohort Study
Authors: Park Seon-Joo , Kim Myung-Sunny , Choi Sang-Woon , Lee Hae-Jeung
Published: December 2020

This study was conducted to investigate the relationship between dietary pattern and genetic risk score (GRS) for dyslipidemia risk among Korean adults. Hypercholesterolemia and hypertriglyceridemia defined as total cholesterol ≥240 mg/dL and triglyceride ≥200 mg/dL or use dyslipidemia medication. The GRS was calculated by summing the risk alleles of the selected seven single-nucleotide polymorphisms related to dyslipidemia. Dietary patterns were identified by principal component analysis based on the frequency of 36 food groups, “whole grain and soybean products” pattern, “meat, fish and vegetables” pattern, and “bread and noodle” pattern were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the multivariate Cox proportional hazards regression model. High intake of a “whole grain and soybean products” pattern decreased risks of hypercholesterolemia (HR: 0.82, 95% CI: 0.72–0.93, p for trend = 0.0006) and hypertriglyceridemia (HR: 0.85, 95% CI: 0.75–0.97, p for trend = 0.0344). In the highest tertile of GRS, the “whole grain and soybean products” pattern was inversely related to hypercholesterolemia risk. Therefore, for people with genotypes that can cause hypercholesterolemia, eating whole grains and soybean products may have a meaningful response, these results could be utilized for genome-based nutrition management.
Interaction Effect of the Mediterranean Diet and an Obesity Genetic Risk Score on Adiposity and Metabolic Syndrome in Adolescents: The HELENA Study
Authors: Seral-Cortes Miguel , Sabroso-Lasa Sergio , De Miguel-Etayo Pilar , Gonzalez-Gross Marcela , Gesteiro Eva , Molina-Hidalgo Cristina , De Henauw Stefaan , Erhardt Éva , Censi Laura , Manios Yannis , Karaglani Eva , Widhalm Kurt , Kafatos Anthony , Beghin Laurent , Meirhaeghe Aline , Salazar-Tortosa Diego , Ruiz Jonatan R. , Moreno Luis A. , Esteban Luis Mariano , Labayen Idoia
Published: December 2020

Obesity and metabolic syndrome (MetS) are worldwide major health challenges. The Mediterranean diet (MD) is associated with a better cardiometabolic profile, but these beneficial effects may be influenced by genetic variations, modulating the predisposition to obesity or MetS. The aim was to assess whether interaction effects occur between an obesity genetic risk score (obesity-GRS) and the MD on adiposity and MetS in European adolescents. Multiple linear regression models were used to assess the interaction effects of an obesity-GRS and the MD on adiposity and MetS and its components. Interaction effects between the MD on adiposity and MetS were observed in both sex groups (p < 0.05). However, those interaction effects were only expressed in a certain number of adolescents, when a limited number of risk alleles were present. Regarding adiposity, a total of 51.1% males and 98.7% females had lower body mass index (BMI) as a result of higher MD adherence. Concerning MetS, only 9.9% of males with higher MD adherence had lower MetS scores. However, the same effect was observed in 95.2% of females. In conclusion, obesity-related genotypes could modulate the relationship between MD adherence and adiposity and MetS in European adolescents; the interaction effect was higher in females than in males.
Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness
Authors: Chandrasekaran Subhiksha , Luna-Vital Diego , de Mejia Elvira Gonzalez
Published: December 2020

The chickpea (Cicer arietinum L.) is one of the most important pulses worldwide. The objective was to identify, compare and evaluate peptides from chickpea hydrolysates produced by two enzymatic treatments. The antidiabetic potential and bitterness of the peptides and induction of bitter receptors were identified in silico. Proteins were isolated from the Kabuli variety. Peptides were produced from the proteins using a simulated digestive system (pepsin/pancreatin, 1:50 Enzyme/Protein, E/P), and these peptides were compared with those produced via bromelain hydrolysis (1:50 E/P). The protein profiles, sequences and characteristics of the peptides were evaluated. The biochemical inhibition and molecular docking of dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase were also studied. The molecular docking identified peptides from enzymatic hydrolysis as inhibitors of DPP-IV. The high hydrophobicity of the peptides indicated the potential for bitterness. There was no correlation between peptide length and DPP-IV binding. Peptides sequenced from the pepsin/pancreatin hydrolysates, PHPATSGGGL and YVDGSGTPLT, had greater affinity for the DPP-IV catalytic site than the peptides from the bromelain hydrolysates. These results are in agreement with their biochemical inhibition, when considering the inhibition of sitagliptin (54.3 µg/mL) as a standard. The bitter receptors hTAS2R38, hTAS2R5, hTAS2R7 and hTAS2R14 were stimulated by most sequences, which could be beneficial in the treatment of type 2 diabetes. Chickpea hydrolysates could be utilized as functional ingredients to be included in the diet for the prevention of diabetes.
Dietary Sources of Melamine Exposure among US Children and Adults in the National Health and Nutrition Examination Survey 2003–2004
Authors: Melough Melissa , Foster Deborah , Fretts Amanda M. , Sathyanarayana Sheela
Published: December 2020

Melamine is a high-production-volume chemical and a kidney toxicant. Diet is a key source of melamine exposure, yet little is known about which foods in the US diet may be contaminated. This study evaluated the associations of foods and dietary patterns with melamine exposure using data from 478 US adults and children from the National Health and Nutrition Examination Survey 2003–2004. Melamine concentrations were measured in spot urine samples. Dietary recalls were used to collect dietary data from the day preceding urine collection. Melamine was detectable (>0.09 ng/mL) in 76.2% of the participants’ urine. The geometric mean urinary melamine was 11.563 µg/g of creatinine (standard error (SE): 1.235). In adjusted linear regression models, each additional ounce of processed meats or whole grains was associated with 10.6% (95% confidence interval (CI): 2.7, 19.0; p = 0.007) or 17.4% (95% CI: 4.7, 31.7; p = 0.006) greater creatinine-adjusted melamine concentrations, respectively. A dietary pattern characterized by high fruit, whole grain, milk, and yogurt intake was positively associated with melamine exposure. In conclusion, processed meats, whole grains, and possibly other plant-based foods may be important melamine sources in the US. Future research should confirm these findings using more recent data and examine the potential health risks of chronic low-level melamine exposure.
COVID-19 and Acute Kidney Injury: A Systematic Review and Meta-Analysis
Authors: Fabrizi Fabrizio , Alfieri Carlo M. , Cerutti Roberta , Lunghi Giovanna , Messa Piergiorgio
Published: December 2020

Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2)—is an ongoing pandemic with high morbidity and mortality rates. Preliminary evidence suggests that acute kidney injury (AKI) is uncommon in patients with COVID-19 and associated with poor outcomes. Study aims and design: we performed a systematic review of the literature with a meta-analysis of clinical studies to evaluate the frequency of AKI and dialysis requirement in patients who underwent hospitalization due to COVID-19. The incidence of AKI according to the death risk was calculated in these patients. The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses. Results: thirty-nine clinical studies (n = 25,566 unique patients) were retrieved. The pooled incidence of AKI was 0.154 (95% CI, 0.107; 0.201; p < 0.0001) across the studies. Significant heterogeneity was found (p = 0.0001). The overall frequency of COVID-19-positive patients who underwent renal replacement therapy (RRT) was 0.043 (95% CI, 0.031; 0.055; p < 0.0001); no publication bias was found (Egger’s test, p = 0.11). The pooled estimate of AKI incidence in patients with severe COVID-19 was 0.53 (95% CI, 0.427; 0.633) and heterogeneity occurred (Q = 621.08, I2 = 97.26, p = 0.0001). According to our meta-regression, age (p < 0.007) and arterial hypertension (p < 0.001) were associated with AKI occurrence in hospitalized COVID-19 positive patients. The odds ratio (OR) for the incidence of AKI in deceased COVID-19 positive patients was greater than among survivors, 15.4 (95% CI, 20.99; 11.4; p < 0.001). Conclusions: AKI is a common complication in hospitalized COVID-19 positive patients. Additional studies are under way to assess the risk of AKI in COVID-19 patients and to deepen the mechanisms of kidney injury.
Prevalence of Aggregatibacter actinomycetemcomitans and Periodontal Findings among 14 to 15-Year Old Danish Adolescents: A Descriptive Cross-Sectional Study
Authors: Jensen Anne Birkeholm , Isidor Flemming , Lund Marianne , Væth Michael , Johansson Anders , Lauritsen Niels Nørskov , Haubek Dorte
Published: December 2020

Aggregatibacter actinomycetemcomitans (Aa) is a keystone pathogen associated with periodontitis in adolescents. The knowledge on the prevalence of Aa and periodontitis among adolescents in Northern Europe is sparse. A total of 525 14- to 15-year-old adolescents from the municipality of Aarhus, Denmark, underwent a full-mouth clinical examination. Plaque score (PS), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. Subgingival plaque samples (SPS) and stimulated saliva samples (SSS) were collected and analyzed for the presence of JP2 and non-JP2 genotypes of Aa using real-time PCR. A total of 70 (13.3%) individuals were positive for Aa, with 17 found in SPS, 19 in SSS, and 35 in both. The highly leukotoxic JP2 genotype of Aa was not detected. The individuals positive for Aa in both SPS and SSS had poorer periodontal outcomes (PPD and CAL) than individuals without Aa and individuals carrying Aa in either SPS or SSS only. In conclusion, 13% of 14- to 15-year-old Danish adolescents were positive for Aa, and the presence of Aa in both SPS and SSS was associated with poorer periodontal outcomes.
N-(Hydroxyalkyl) Derivatives of tris(1H-indol-3-yl)methylium Salts as Promising Antibacterial Agents: Synthesis and Biological Evaluation
Authors: Lavrenov Sergey N. , Isakova Elena B. , Panov Alexey A. , Simonov Alexander Y. , Tatarskiy Viktor V. , Trenin Alexey S.
Published: December 2020

The wide spread of pathogens resistance requires the development of new antimicrobial agents capable of overcoming drug resistance. The main objective of the study is to elucidate the effect of substitutions in tris(1H-indol-3-yl)methylium derivatives on their antibacterial activity and toxicity to human cells. A series of new compounds were synthesized and tested. Their antibacterial activity in vitro was performed on 12 bacterial strains, including drug resistant strains, that were clinical isolates or collection strains. The cytotoxic effect of the compounds was determined using an test with HPF-hTERT (human postnatal fibroblasts, immortalized with hTERT) cells. The activity of the obtained compounds depended on the carbon chain length. Derivatives with C5–C6 chains were more active. The minimum inhibitory concentration (MIC) of the most active compound on Gram-positive bacteria, including MRSA, was 0.5 μg/mL. Compounds with C5–C6 chains also revealed high activity against Staphylococcus epidermidis (1.0 and 0.5 μg/mL, respectively) and moderate activity against Gram-negative bacteria Escherichia coli (8 μg/mL) and Klebsiella pneumonia (2 and 8 μg/mL, respectively). However, they have no activity against Salmonella cholerasuis and Pseudomonas aeruginosa. The most active compounds revealed higher antibacterial activity on MRSA than the reference drug levofloxacin, and their ratio between antibacterial and cytotoxic activity exceeded 10 times. The data obtained provide a basis for further study of this promising group of substances.
Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis
Authors: Montalvo-Quirós Sandra , Vallet-Regí María , Palacios Ainhoa , Anguita Juan , Prados-Rosales Rafael C. , González Blanca , Luque-Garcia Jose L.
Published: December 2020

The increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics constitute a public health issue, since tuberculosis still constitutes the primary cause of death in the world due to bacterial infection. Mtb has been shown to produce membrane-derived extracellular vesicles (EVs) containing proteins responsible for modulating the pathological immune response after infection. These natural vesicles were considered a promising alternative to the development of novel vaccines. However, their use was compromised by the observed lack of reproducibility between preparations. In this work, with the aim of developing nanosystems mimicking the extracellular vesicles produced by Mtb, mesoporous silica nanoparticles (MSNs) have been used as nanocarriers of immunomodulatory and vesicle-associated proteins (Ag85B, LprG and LprA). These novel nanosystems have been designed and extensively characterized, demonstrating the effectiveness of the covalent anchorage of the immunomodulatory proteins to the surface of the MSNs. The immunostimulatory capacity of the designed nanosystems has been demonstrated by measuring the levels of pro- (TNF) and anti-inflammatory (IL-10) cytokines in exposed macrophages. These results open a new possibility for the development of more complex nanosystems, including additional vesicle components or even antitubercular drugs, thus allowing for the combination of immunomodulatory and bactericidal effects against Mtb.
Use of Alfentanil in Palliative Care
Authors: Ferraz Gonçalves José António , Sousa Filipa , Alves Lucy , Liu Patrícia , Coelho Sara
Published: December 2020

Alfentanil is used for chronic pain relief in palliative care. However, there is a dearth of data on its use. For this reason, a decision was made to review the use of alfentanil in palliative care. Retrospective study was carried out in a palliative care service. The files of patients who received alfentanil as an intravenous or subcutaneous continuous infusion for pain relief, between January 2018 and April 2019. In total, 111 patients received alfentanil out of 113 admissions. Of them, 56 were male, and the median age was 70 years. The median number of days on alfentanil was 6 (range 1 to 129). The most frequent primary reasons for switching to alfentanil was uncontrolled pain in 52 (46%) patients and renal impairment in 24 (21%) patients. The median 24-h initial dose of alfentanil was 4 mg (1–20), and the median final 24-h dose of alfentanil was 5 mg (1–60), (p < 0.001). The initial 24-h median number of rescue doses was 2 (0–8), and the final median number of rescue doses was 1 (0 to 8), (p = 0.025). In 56 patients who were on alfentanil for at least 7 days, the dose decreased in 3 (5%), remained stable in 10 (18%) and increased in 43 (77%). The patient on alfentanil for 129 days maintained the same dose throughout that period. Alfentanil can be a useful second-line opioid. The induction of tolerance does not seem to be particularly rapid with alfentanil.
Study on Temperature-Dependent Properties and Fire Resistance of Metakaolin-Based Geopolymer Foams
Authors: Le Van Su , Louda Petr , Tran Huu Nam , Nguyen Phu Dong , Bakalova Totka , Ewa Buczkowska Katarzyna , Dufkova Iva
Published: December 2020

This paper presents temperature-dependent properties and fire resistance of geopolymer foams made of ground basalt fibers, aluminum foaming agents, and potassium-activated metakaolin-based geopolymers. Temperature-dependent properties of basalt-reinforced geopolymer foams (BGFs) were investigated by a series of measurements, including apparent density, water absorption, mass loss, drying shrinkage, compressive and flexural strengths, XRD, and SEM. Results showed that the apparent density and drying shrinkage of the BGFs increase with increasing the treated temperature from 400 to 1200 °C. Below 600 °C the mass loss is enhanced while the water absorption is reduced and they both vary slightly between 600 and 1000 °C. Above 1000 °C the mass loss is decreased rapidly, whereas the water absorption is increased. The compressive and flexural strengths of the BGFs with high fiber content are improved significantly at temperatures over 600 °C and achieved the maximum at 1200 °C. The BGF with high fiber loading at 1200 °C exhibited a substantial increase in compressive strength by 108% and flexural strength by 116% compared to that at room temperature. The enhancement in the BGF strengths at high temperatures is attributed to the development of crystalline phases and structural densification. Therefore, the BGFs with high fiber loading have extraordinary mechanical stability at high temperatures. The fire resistance of wood and steel plates has been considerably improved after coating a BGF layer on their surface. The coated BGF remained its structural integrity without any considerable macroscopic damage after fire resistance test. The longest fire-resistant times for the wood and steel plates were 99 and 134 min, respectively. In general, the BGFs with excellent fire resistance have great potential for fire protection applications.