bluuebunny/crossref_metadata_2025 huggingface dataset:
Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery
Authors: Ueno Yuji , Hira Kenichiro , Miyamoto Nobukazu , Kijima Chikage , Inaba Toshiki , Hattori Nobutaka
Published: September 2020

Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.
Altered Regulation of adipomiR Editing with Aging
Authors: Meadows Sabel , Seidler Abbagael , Wall Madison , Page Jamika , Taylor Cara , Flinn Brendin , Turner Robin , Santanam Nalini
Published: September 2020

Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging.
Expression of Fbp2, a Newly Discovered Constituent of Memory Formation Mechanisms, Is Regulated by Astrocyte–Neuron Crosstalk
Authors: Hajka Daria , Duda Przemysław , Wójcicka Olga , Drulis-Fajdasz Dominika , Rakus Dariusz , Gizak Agnieszka
Published: September 2020

Fbp2 (muscle isozyme of fructose 1,6-bisphosphatase) is a glyconeogenesis-regulating enzyme and a multifunctional protein indispensable for long-term potentiation (LTP) formation in the hippocampus. Here, we present evidence that expression of Fbp2 in murine hippocampal cell cultures is regulated by crosstalk between neurons and astrocytes. Co-culturing of the two cell types results in a decrease in Fbp2 expression in astrocytes, and its simultaneous increase in neurons, as compared to monocultures. These changes are regulated by paracrine signaling using extracellular vesicle (EV)-packed factors released to the culture medium. It is well accepted that astrocyte–neuron metabolic crosstalk plays a crucial role in shaping neuronal function, and recently we have suggested that Fbp2 is a hub linking neuronal signaling with redox and/or energetic state of brain during the formation of memory traces. Thus, our present results emphasize the importance of astrocyte–neuron crosstalk in the regulation of the cells’ metabolism and synaptic plasticity, and bring us one step closer to a mechanistic understanding of the role of Fbp2 in these processes.
Classifications of Neurodegenerative Disorders Using a Multiplex Blood Biomarkers-Based Machine Learning Model
Authors: Lin Chin-Hsien , Chiu Shu-I , Chen Ta-Fu , Jang Jyh-Shing Roger , Chiu Ming-Jang
Published: September 2020

Easily accessible biomarkers for Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), and related neurodegenerative disorders are urgently needed in an aging society to assist early-stage diagnoses. In this study, we aimed to develop machine learning algorithms using the multiplex blood-based biomarkers to identify patients with different neurodegenerative diseases. Plasma samples (n = 377) were obtained from healthy controls, patients with AD spectrum (including mild cognitive impairment (MCI)), PD spectrum with variable cognitive severity (including PD with dementia (PDD)), and FTD. We measured plasma levels of amyloid-beta 42 (Aβ42), Aβ40, total Tau, p-Tau181, and α-synuclein using an immunomagnetic reduction-based immunoassay. We observed increased levels of all biomarkers except Aβ40 in the AD group when compared to the MCI and controls. The plasma α-synuclein levels increased in PDD when compared to PD with normal cognition. We applied machine learning-based frameworks, including a linear discriminant analysis (LDA), for feature extraction and several classifiers, using features from these blood-based biomarkers to classify these neurodegenerative disorders. We found that the random forest (RF) was the best classifier to separate different dementia syndromes. Using RF, the established LDA model had an average accuracy of 76% when classifying AD, PD spectrum, and FTD. Moreover, we found 83% and 63% accuracies when differentiating the individual disease severity of subgroups in the AD and PD spectrum, respectively. The developed LDA model with the RF classifier can assist clinicians in distinguishing variable neurodegenerative disorders.
Thermally Stable Nitrothiacalixarene Chromophores: Conformational Study and Aggregation Behavior
Authors: Muravev Anton , Gerasimova Tatiana , Fayzullin Robert , Babaeva Olga , Rizvanov Ildar , Khamatgalimov Ayrat , Kadirov Marsil , Katsyuba Sergey , Litvinov Igor , Latypov Shamil , Solovieva Svetlana , Antipin Igor
Published: September 2020

Achieving high thermal stability and control of supramolecular organization of functional dyes in sensors and nonlinear optics remains a demanding task. This study was aimed at the evaluation of thermal behavior and Langmuir monolayer characteristics of topologically varied nitrothiacalixarene multichromophores and phenol monomers. A nitration/azo coupling alkylation synthetic route towards partially O-substituted nitrothiacalixarenes and 4-nitrophenylazo-thiacalixarenes was proposed and realized. Nuclear magnetic resonance (NMR) spectroscopy and X-ray diffractometry of disubstituted nitrothiacalix[4]arene revealed a rare 1,2-alternate conformation. A synchronous thermal analysis indicated higher decomposition temperatures of nitrothiacalixarene macrocycles as compared with monomers. Through surface pressure/potential-molecular area measurements, nitrothiacalixarenes were shown to form Langmuir monolayers at the air–water interface and, through atomic force microscopy (AFM) technique, Langmuir–Blodgett (LB) films on solid substrates. Reflection-absorption spectroscopy of monolayers and electronic absorption spectroscopy of LB films of nitrothiacalixarenes recorded a red-shifted band (290 nm) with a transition from chloroform, indicative of solvatochromism. Additionally, shoulder band at 360 nm was attributed to aggregation and supported by gas-phase density functional theory (DFT) calculations and dynamic light scattering (DLS) analysis in chloroform–methanol solvent in the case of monoalkylated calixarene 3. Excellent thermal stability and monolayer formation of nitrothiacalixarenes suggest their potential as functional dyes.
Cellular and Molecular Aspects of Anti-Melanoma Effect of Minocycline—A Study of Cytotoxicity and Apoptosis on Human Melanotic Melanoma Cells
Authors: Rok Jakub , Rzepka Zuzanna , Beberok Artur , Pawlik Justyna , Wrześniok Dorota
Published: September 2020

Minocycline is a tetracycline compound with pleiotropic pharmacological properties. In addition to its antibacterial action, it shows many non-antimicrobial effects, including an anti-cancer activity. The anti-cancer action was confirmed in studies on ovarian carcinoma cells, hepatocellular carcinoma cells, glioma cells, or acute myeloid leukemia cells. Malignant melanoma remains a serious medical problem despite the extensive knowledge of the disease. The low effectiveness of the standard treatment, as well as the resistance to therapy, result in high mortality rates. This work aimed to investigate the potential and mechanisms of anti-melanoma action of minocycline. Human skin melanotic melanoma cell line COLO 829 was used in the study. The obtained results showed that minocycline decreased cell viability and inhibited the growth of melanoma cells, proportional to the drug concentration as well as to the time of incubation. The EC50 values were calculated to be 78.6 µM, 31.7 µM, and 13.9 µM for 24 h, 48 h, and 72 h, respectively. It was observed that treated cells had a disturbed cell cycle and significantly changed morphology. Moreover, minocycline caused a decrease in mitochondrial membrane potential and an increase in cells with a low level of reduced thiols. Finally, it was found that the anti-melanoma effect of minocycline was related to the induction of apoptosis. The drug activated caspases 8, 9, and 3/7 as well as increased the number of annexin V-positive cells. The presented results show that minocycline possesses anti-melanoma potential.
PTBP1 Positively Regulates the Translation of Circadian Clock Gene, Period1
Authors: Kim Wanil , Shin Jae-Cheon , Lee Kyung-Ha , Kim Kyong-Tai
Published: September 2020

Circadian oscillations of mRNAs and proteins are the main features of circadian clock genes. Among them, Period1 (Per1) is a key component in negative-feedback regulation, which shows a robust diurnal oscillation and the importance of circadian rhythm and translational regulation of circadian clock genes has been recognized. In the present study, we investigated the 5′-untranslated region (5′-UTR) of the mouse core clock gene, Per1, at the posttranscriptional level, particularly its translational regulation. The 5′-UTR of Per1 was found to promote its translation via an internal ribosomal entry site (IRES). We found that polypyrimidine tract-binding protein 1 (PTBP1) binds to the 5′-UTR of Per1 and positively regulates the IRES-mediated translation of Per1 without affecting the levels of Per1 mRNA. The reduction of PTBP1 level also decreased the endogenous levels of the PER1 protein but not of its mRNA. As for the oscillation of PER1 expression, the disruption of PTBP1 levels lowered the PER1 expression but not the phase of the oscillation. PTBP1 also changed the amplitudes of the mRNAs of other circadian clock genes, such as Cryptochrome 1 (Cry1) and Per3. Our results suggest that the PTBP1 is important for rhythmic translation of Per1 and it fine-tunes the overall circadian system.
The Role of Artificial Intelligence, MLR and Statistical Analysis in Investigations about the Correlation of Swab Tests and Stress on Health Care Systems by COVID-19
Authors: Pirouz Behzad , Nejad Hana Javadi , Violini Galileo , Pirouz Behrouz
Published: September 2020

The outbreak of the new Coronavirus (COVID-19) pandemic has prompted investigations on various aspects. This research aims to study the possible correlation between the numbers of swab tests and the trend of confirmed cases of infection, while paying particular attention to the sickness level. The study is carried out in relation to the Italian case, but the result is of more general importance, particularly for countries with limited ICU (intensive care units) availability. The statistical analysis showed that, by increasing the number of tests, the trend of home isolation cases was positive. However, the trend of mild cases admitted to hospitals, intensive case cases, and daily deaths were all negative. The result of the statistical analysis provided the basis for an AI study by ANN. In addition, the results were validated using a multivariate linear regression (MLR) approach. Our main result was to identify a significant statistical effect of a reduction of pressure on the health care system due to an increase in tests. The relevance of this result is not confined to the COVID-19 outbreak, because the high demand of hospitalizations and ICU treatments due to this pandemic has an indirect effect on the possibility of guaranteeing an adequate treatment for other high-fatality diseases, such as, e.g., cardiological and oncological ones. Our results show that swab testing may play a significant role in decreasing stress on the health system. Therefore, this case study is relevant, in particular, for plans to control the pandemic in countries with a limited capacity for admissions to ICU units.
Pilot Study on the Use of a Laser-Structured Double Diamond Electrode (DDE) for Biofilm Removal from Dental Implant Surfaces
Authors: Koch Maximilian , Burkovski Andreas , Zulla Manuel , Rosiwal Stefan , Geißdörfer Walter , Dittmar Roman , Grobecker-Karl Tanja
Published: September 2020

No proper treatment option for peri-implantitis exists yet. Based on previous studies showing the in vitro effectiveness of electrochemical disinfection using boron-doped diamond electrodes, novel double diamond electrodes (DDE) were tested here. Using a ceramic carrier and a laser structuring process, a clinically applicable electrode array was manufactured. Roughened metal discs (n = 24) made from Ti-Zr alloy were exposed to the oral cavities of six volunteers for 24 h in order to generate biofilm. Then, biofilm removal was carried out either using plastic curettes and chlorhexidine digluconate or electrochemical disinfection. In addition, dental implants were contaminated with ex vivo multispecies biofilm and disinfected using DDE treatment. Bacterial growth and the formation of biofilm polymer were determined as outcome measures. Chemo-mechanical treatment could not eliminate bacteria from roughened surfaces, while in most cases, a massive reduction of bacteria and biofilm polymer was observed following DDE treatment. Electrochemical disinfection was charge- and time-dependent and could also not reach complete disinfection in all instances. Implant threads had no negative effect on DDE treatment. Bacteria exhibit varying resistance to electrochemical disinfection with Bacillus subtilis, Neisseria sp., Rothiamucilaginosa, Staphylococcus haemolyticus, and Streptococcus mitis surviving 5 min of DDE application at 6 V. Electrochemical disinfection is promising but requires further optimization with respect to charge quantity and application time in order to achieve disinfection without harming host tissue.
Performance Analysis of Combined Cycle with Air Breathing Derivative Gas Turbine, Heat Recovery Steam Generator, and Steam Turbine as LNG Tanker Main Engine Propulsion System
Authors: Nirbito Wahyu , Budiyanto Muhammad Arif , Muliadi Robby
Published: September 2020

This study explains the performance analysis of a propulsion system engine of an LNG tanker using a combined cycle whose components are gas turbine, steam turbine, and heat recovery steam generator. The researches are to determine the total resistance of an LNG tanker with a capacity of 125,000 m3 by using the Maxsurf Resistance 20 software, as well as to design the propulsion system to meet the required power from the resistance by using the Cycle-Tempo 5.0 software. The simulation results indicate a maximum power of the system of about 28,122.23 kW with a fuel consumption of about 1.173 kg/s and a system efficiency of about 48.49% in fully loaded conditions. The ship speed can reach up to 20.67 knots.
Retrospective CT/MRI Texture Analysis of Rapidly Progressive Hepatocellular Carcinoma
Authors: Kim Charissa , Cigarroa Natasha , Surabhi Venkateswar , Ganeshan Balaji , Pillai Anil K.
Published: September 2020

Rapidly progressive hepatocellular carcinoma (RPHCC) is a subset of hepatocellular carcinoma that demonstrates accelerated growth, and the radiographic features of RPHCC versus non-RPHCC have not been determined. The purpose of this retrospective study was to use baseline radiologic features and texture analysis for the accurate detection of RPHCC and subsequent improvement of clinical outcomes. We conducted a qualitative visual analysis and texture analysis, which selectively extracted and enhanced imaging features of different sizes and intensity variation including mean gray-level intensity (mean), standard deviation (SD), entropy, mean of the positive pixels (MPP), skewness, and kurtosis at each spatial scaling factor (SSF) value of RPHCC and non-RPHCC tumors in a computed tomography (CT) cohort of n = 11 RPHCC and n = 11 non-RPHCC and a magnetic resonance imaging (MRI) cohort of n = 13 RPHCC and n = 10 non-RPHCC. There was a statistically significant difference across visual CT irregular margins p = 0.030 and CT texture features in SSF between RPHCC and non-RPHCC for SSF-6, coarse-texture scale, mean p = 0.023, SD p = 0.053, MPP p = 0.023. A composite score of mean SSF-6 binarized + SD SSF-6 binarized + MPP SSF-6 binarized + irregular margins was significantly different between RPHCC and non-RPHCC (p = 0.001). A composite score ≥3 identified RPHCC with a sensitivity of 81.8% and specificity of 81.8% (AUC = 0.884, p = 0.002). CT coarse-texture-scale features in combination with visually detected irregular margins were able to statistically differentiate between RPHCC and non-RPHCC. By developing an image-based, non-invasive diagnostic criterion, we created a composite score that can identify RPHCC patients at their early stages when they are still eligible for transplantation, improving the clinical course of patient care.
The Investment Performance of Ethical Equity Funds in Malaysia
Authors: Mansor Fadillah , Bhatti M. Ishaq , Rahman Shafiqur , Do Hung Quang
Published: September 2020

This paper investigates the investment performance of Malaysian Islamic equity funds and a matching sample of conventional equity funds relative to their market benchmark. An integrated model is used to simultaneously capture the market timing and selectivity skills of fund managers. Our findings indicate that the Islamic funds do not match the performance of the conventional funds in terms of selectivity skill. However, Islamic funds perform no worse than their conventional counterparts in market timing, although neither outperform the market. These findings have crucial implications not only for fund managers’ investment decisions, but also for sensitive shariah-compliant investors and risk-seeking investors of Islamic equity funds in their investment portfolio preference.
Mapping the Scientific Research on Mass Customization Domain: A Critical Review and Bibliometric Analysis
Authors: Baranauskas Gedas , Raišienė Agota Giedrė , Korsakienė Renata
Published: September 2020

Researchers of the Mass Customization domain face not only challenges of proper and timeless identification of latest practical trends, but also difficulties in rational analyses on the numerous existing scientific studies in this field as well as a need for a comprehensive and multidimensional state-of-the-art overview of the Mass Customization research domain in the last three decades. Therefore, the present research article aims to provide a critical standpoint and reveal the main research directions and content at systemic, bibliometric and historical research levels in the period of 1990–2020. Four types of bibliometric clustering techniques and a visualization of results in a format of two-dimensional maps by the VOSviewer software were applied in the analysis on 1783 scientific papers from the Clarivate Analytics Web of Science Core Collection. The analysis reveals six historical periods in the Mass Customization research domain, from which, in the last three decades, three are identified as influencing modern Mass Customization research areas and objects. Results confirmed a shift from a stand-alone scientific approach to the customization of tangible products in the manufacturing field and their risk management, to a hybrid scientific approach with a focus on the customization of non-tangible products and personalized customer behavior in online environments.
Where Freshness Matters in the Control Loop: Mixed Age-of-Information and Event-Based Co-Design for Multi-Loop Networked Control Systems
Authors: Mamduhi Mohammad H. , Champati Jaya Prakash , Gross James , Johansson Karl H.
Published: September 2020

In the design of multi-loop Networked Control Systems (NCSs), wherein each control system is characterized by heterogeneous dynamics and associated with a certain set of timing specifications, appropriate metrics need to be employed for the synthesis of control and networking policies to efficiently respond to the requirements of each control loop. The majority of the design approaches for sampling, scheduling, and control policies include either time-based or event-based metrics to perform pertinent actions in response to the changes of the parameters of interest. We specifically focus in this article on Age-of-Information (AoI) as a recently-developed time-based metric and threshold-based triggering function as a generic Event-Triggered (ET) metric. We consider multiple heterogeneous stochastic linear control systems that close their feedback loops over a shared communication network. We investigate the co-design across the NCS and discuss the pros and cons with the AoI and ET approaches in terms of asymptotic control performance measured by Linear-Quadratic Gaussian (LQG) cost functions. In particular, sampling and scheduling policies combining AoI and stochastic ET metrics are proposed. It is argued that pure AoI functions that generate decision variables solely upon minimizing the average age irrespective of control systems dynamics may not be able to improve the overall NCS performance even compared with purely randomized policies. Our theoretical analysis is validated through several simulation scenarios.
On \({\mathcal{F}}\)-Contractions for Weak α-Admissible Mappings in Metric-Like Spaces
Authors: Vujaković Jelena , Mitrović Slobodanka , Mitrović Zoran , Radenović Stojan
Published: September 2020

In the paper, we consider some fixed point results of F-contractions for triangular α-admissible and triangular weak α-admissible mappings in metric-like spaces. The results on F-contraction type mappings in the context of metric-like spaces are generalized, improved, unified, and enriched. We prove the main result but using only the property (F1) of the strictly increasing mapping F:0,+∞→−∞,+∞. Our approach gives a proper generalization of several results given in current literature.
Virtual Screening of Marine Natural Compounds by Means of Chemoinformatics and CDFT-Based Computational Peptidology
Authors: Flores-Holguín Norma , Frau Juan , Glossman-Mitnik Daniel
Published: September 2020

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the theopapuamides A-D family of marine peptides by making use of our proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular system. CP allows for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea about the chemical reactivity properties of the marine natural products under study, which are expected to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans In DFT) technique, as well as the MN12SX/Def2TZVP/H2O model chemistry is successfully verified. Together with several chemoinformatic tools that can be used to improve the process of virtual screening, some additional properties of these marine peptides are identified related to their ability to behave as useful drugs. With the further objective of analyzing their bioactivity, some useful parameters for future QSAR studies, their predicted biological targets, and the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the theopapuamides A-D pharmacokinetics are also reported.
Allometric Modeling of Wingate Test among Adult Male Athletes from Combat Sports
Authors: Coelho-e-Silva Manuel J. , Sousa-e-Silva Paulo , Morato Vinícius S. , Costa Daniela C. , Martinho Diogo V. , Rama Luís M. , Valente-dos-Santos João , Werneck André O. , Tavares Óscar M. , Conde Jorge , Castanheira Joaquim M. , Soles-Gonçalves Rui , Duarte João P.
Published: September 2020

Background and objectives: Athletes from combat sports are grouped into a series of weight categories that are intended to promote fair competition. Differences in performance are partly attributable to differences in body size. Consequently, ratio standards in which a performance variable is simply divided by an anthropometric characteristic such as body mass are often used, although this application is not recommended. This study aimed to obtain allometric models to interpret Wingate Anaerobic Test (WAnT) outputs among male adult athletes from combat sports. Materials and Methods: The sample was composed of 64 participants aged 18–39 years (24.2 ± 4.6 years). Stature and body mass (BM) were measured and air displacement plethysmography used to estimate fat mass and fat-free mass (FFM). Lower-limb lean soft tissue (LL-LST) was derived from dual energy X-ray absorptiometry. WAnT outputs were peak power (WAnT-PP) and mean power (WAnT-MP). Allometric models were obtained from simple and multiple linear regressions using log-transformed variables. Results: Models derived from a single three-dimension descriptor explained a large portion of variance: WAnT-PP (BM: 31.1%; FFM: 54%; LL-LST: 47.2%) and WAnT-MP (BM: 50.1%; FFM: 57.4%; LL-LST: 62.7%). Finally, the best proportional allometric models emerged from the combination of LL-LST and FFM (WAnT-PP: 55%; WAnT-MP: 65%). Conclusions: The relationship between weight categories and performance did not seem to be explained by the basic principles of geometric similarity.
Editorial for the Special Issue on the ICAE 2019
Authors: Choi Hongsoo , Lee Dong-Weon , Lee Jeong-Bong , Kim Sang-Jae
Published: September 2020

This special issue is a collection of 10 selected papers after presenting at the Fifth International Conference on Advanced Electromaterials (ICAE 2019), held in Jeju, South Korea on 5–8 November 2019 [...]
Adenosine Receptor Ligands: Coumarin–Chalcone Hybrids as Modulating Agents on the Activity of hARs
Authors: Vazquez-Rodriguez Saleta , Vilar Santiago , Kachler Sonja , Klotz Karl-Norbert , Uriarte Eugenio , Borges Fernanda , Matos Maria João
Published: September 2020

Adenosine receptors (ARs) play an important role in neurological and psychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy and schizophrenia. The different subtypes of ARs and the knowledge on their densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Looking for new scaffolds for selective AR ligands, coumarin–chalcone hybrids were synthesized (compounds 1–8) and screened in radioligand binding (hA1, hA2A and hA3) and adenylyl cyclase (hA2B) assays in order to evaluate their affinity for the four human AR subtypes (hARs). Coumarin–chalcone hybrid has been established as a new scaffold suitable for the development of potent and selective ligands for hA1 or hA3 subtypes. In general, hydroxy-substituted hybrids showed some affinity for the hA1, while the methoxy counterparts were selective for the hA3. The most potent hA1 ligand was compound 7 (Ki = 17.7 µM), whereas compound 4 was the most potent ligand for hA3 (Ki = 2.49 µM). In addition, docking studies with hA1 and hA3 homology models were established to analyze the structure–function relationships. Results showed that the different residues located on the protein binding pocket could play an important role in ligand selectivity.
Design, Synthesis, and Structure–Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer’s Disease
Authors: Sağlık Begüm Nurpelin , Osmaniye Derya , Acar Çevik Ulviye , Levent Serkan , Kaya Çavuşoğlu Betül , Özkay Yusuf , Kaplancıklı Zafer Asım
Published: September 2020

Dementia is a neurological condition commonly correlated with Alzheimer’s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a–2l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 ± 0.003, 0.056 ± 0.002, 0.147 ± 0.006, 0.040 ± 0.001, 0.031 ± 0.001, 0.028 ± 0.001, and 0.138 ± 0.005 µM, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 ± 0.001 µM, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.
Controlled Release of Pyrimidine Compound Using Polymeric Coated ZIF-8 Metal-Organic Framework as Glucagon-Like Peptide-1 Receptor Agonist Carrier
Authors: AlNeyadi Shaikha S. , Amir Naheed , Ghattas Mohammad A. , Atatreh Noor , Alketbi Shaikha S. , Ajeil Ruba Al , Adem Abdu
Published: September 2020

This work demonstrates synthetic strategies for the incorporation of a synthesized pyrimidine glucagon-like peptide-1 (GLP-1) agonist into alginate-coated ZIF-8. The prepared pyrimidine GLP-1 agonist used for the treatment of diabetes type II, was trapped inside polymer coated ZIF-8. The encapsulation of the GLP-1 agonist was confirmed by UV-visible and FT-IR spectroscopies. Furthermore, the release kinetics of GLP-1 agonist drug from alginate-coated ZIF-8 were investigated in phosphate-buffered saline at 37 °C at pH 8 and 1.5. The alginate-coated ZIF-8 exhibited much faster drug release at basic pH than at pH 1.5, indicating the potential of the alginate-coated ZIF-8 system to overcome the fast degradation at acidic pH of the stomach and improve the drug’s activity. This study may open the way for the synthesis of new metal organic frameworks (MOFs) to enhance drug delivery systems.
Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use
Authors: Uranga José Antonio , Martínez Vicente , Abalo Raquel
Published: September 2020

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.
Lipid Profile Modulates Cardiometabolic Risk Biomarkers Including Hypertension in People with Type-2 Diabetes: A Focus on Unbalanced Ratio of Plasma Polyunsaturated/Saturated Fatty Acids
Authors: Gouaref Ines , Bouazza Asma , Abderrhmane Samir Ait , Koceir Elhadj-Ahmed
Published: September 2020

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio is a likely contributor, but the mechanisms involved are not clearly elucidated. The aim of this study is to explore the association between plasma SFA/PUFA ratio and the clusters of cardiometabolic syndrome (CMS), including the atherogenic biomarkers, inflammatory status, feeding patterns, and physical activity in people with T2DM with or without essential hypertension. The study was conducted on 784 adult male and female participants, aged between 30 and 50 years, and divided into 3 groups: 100 T2DM without hypertension (D); 368 T2DM with hypertension (DM); and 316 hypertensive participants without T2DM (H). All Participants were phenotyped regarding CMS clusters according to the NCEP/ATPIII criteria. Insulin resistance was assessed by Homeostasis model assessment (HOMA model). Metabolic, atherogenic, and inflammatory parameters were analyzed by biochemical methods; NEFFA by microfluorimetry; SFA, PUFA-n6 and PUFA-n3 by gas phase chromatography. Dietary lipids and physical activity were analyzed through the use of validated questionnaires. The clusters of CMS were found in all groups. Dyslipidemia was correlated with accretion NEFFA levels in all groups, but more accentuated in the DH group (r = +0.77; p < 0.001). Similarly, plasma PUFA/SFA ratio and PUFA-3 level was lower, concomitantly with a higher plasma ApoB100/ApoA1 (p < 0.001), lipoprotein (a), homocysteine (p < 0.001), and pro-inflammatory cytokines (TNFα, IL-6, IL1-β) in the DH group. Likewise, the depletion of PUFA-n3/PUFA-n6 ratio is associated with the decrease of omega 3-DHA (docosahexaenoic acid) and omega 3-EPA (eicosapentaenoic acid) (p < 0.001). It appears that the PUFAs-n3 ratio modulates cardiometabolic risk, inflammatory state and atherogenic biomarkers. The plasma unbalanced ratio of SFA/PUFA reflects dietary fatty acids intake. The contribution of dietary lipids is undisputed. Nutritional recommendations are required to determine the fatty acids ratio (saturated and unsaturated) provided in the diet.
Contribution of the Multiplicity Fluctuation in the Temperature Dependence of Phonon Spectra of Rare-Earth Cobaltites
Authors: Orlov Yuri S. , Sokolov Alexey E. , Dudnikov Vyacheslav A. , Shulga Karina V. , Volochaev Mikhail N. , Zharkov Sergey M. , Shestakov Nikolay P. , Vysotin Maxim A. , Ovchinnikov Sergei G.
Published: September 2020

We have studied, both experimentally and theoretically, the unusual temperature dependence of the phonon spectra in NdCoO3, SmCoO3 and GdCoO3, where the Co3+ ion is in the low-spin (LS) ground state, and at the finite temperature, the high-spin (HS) term has a nonzero concentration nHS due to multiplicity fluctuations. We measured the absorption spectra in polycrystalline and nanostructured samples in the temperature range 3–550 K and found a quite strong breathing mode softening that cannot be explained by standard lattice anharmonicity. We showed that the anharmonicity in the electron–phonon interaction is responsible for this red shift proportional to the nHS concentration.
The Effects of Flavonoids in Cardiovascular Diseases
Authors: Ciumărnean Lorena , Milaciu Mircea Vasile , Runcan Octavia , Vesa Ștefan Cristian , Răchișan Andreea Liana , Negrean Vasile , Perné Mirela-Georgiana , Donca Valer Ioan , Alexescu Teodora-Gabriela , Para Ioana , Dogaru Gabriela
Published: September 2020

Flavonoids are metabolites of plants and fungus. Flavonoid research has been paid special attention to in recent times after the observation of their beneficial effects on the cardiovascular system. These favorable effects are exerted by flavonoids mainly due to their antioxidant properties, which result from the ability to decrease the oxidation of low-density lipoproteins, thus improving the lipid profiles. The other positive effect exerted on the cardiovascular system is the ability of flavonoids to produce vasodilation and regulate the apoptotic processes in the endothelium. Researchers suggested that these effects, including their anti-inflammatory function, are consequences of flavonoids’ potent antioxidant properties, but recent studies have shown multiple signaling pathways linked to them, thus suggesting that there are more mechanisms involved in the beneficial effect of the flavonoids on the human body. This review aims to present the latest data on the classification of these substances, their main mechanisms of action in the human body, and the beneficial effects on the physiological and pathological status of the cardiovascular system.
Skin Damages—Structure Activity Relationship of Benzimidazole Derivatives Bearing a 5-Membered Ring System
Authors: Djuidje Ernestine Nicaise , Durini Elisa , Sciabica Sabrina , Serra Elena , Balzarini Jan , Liekens Sandra , Manfredini Stefano , Vertuani Silvia , Baldisserotto Anna
Published: September 2020

In the search for scaffolds for multifunctional compounds we investigated the structure activity relationship of a class of benzimidazole derivatives bearing 5-membered ring. The newly synthesized and the already known compounds were divided into three classes that present different substituent at 5 position of the benzimidazole ring (-H, -COOH or –SO3H) and different heterocycle at position 2 (thiophene, furan or pyrrole). All the derivatives were synthesized and tested to determine their photoprotective profile against UV rays, in vitro antioxidant capacity against different radicals (DPPH and FRAP test), antifungal inhibitory activity (dermatophytes and Candida albicans), antiviral and antiproliferative activity. A Structure-Activity Relationship study indicated compound 10, bearing a pyrrole heterocycle on the benzimidazole ring, as the best multifunctional derivative of the series and as potential candidate for the development of drugs especially in case of melanoma.
Synergistic Solubilization of Phenanthrene by Mixed Micelles Composed of Biosurfactants and a Conventional Non-Ionic Surfactant
Authors: Liu Jianfei , Wang Yuru , Li Huifang
Published: September 2020

This study investigated the solubilization capabilities of rhamnolipids biosurfactant and synthetic surfactant mixtures for the application of a mixed surfactant in surfactant-enhanced remediation. The mass ratios between Triton X-100 and rhamnolipids were set at 1:0, 9:1, 3:1, 1:1, 1:3, and 0:1. The ideal critical micelle concentration values of the Triton X-100/rhamnolipids mixture system were higher than that of the theoretical predicted value suggesting the existence of interactions between the two surfactants. Solubilization capabilities were quantified in term of weight solubilization ratio and micellar-water partition coefficient. The highest value of the weight solubilization ratio was detected in the treatment where only Triton X-100 was used. This ratio decreased with the increase in the mass of rhamnolipids in the mixed surfactant systems. The parameters of the interaction between surfactants and the micellar mole fraction in the mixed system have been determined. The factors that influence phenanthrene solubilization, such as pH, ionic strength, and acetic acid concentration have been discussed in the paper. The aqueous solubility of phenanthrene increased linearly with the total surfactant concentration in all treatments. The mixed rhamnolipids and synthetic surfactants showed synergistic behavior and enhanced the solubilization capabilities of the mixture, which would extend the rhamnolipids application.
Techno-Economic Analysis of Producing Glacial Acetic Acid from Poplar Biomass via Bioconversion
Authors: Morales-Vera Rodrigo , Crawford Jordan , Dou Chang , Bura Renata , Gustafson Rick
Published: September 2020

Most of the current commercial production of glacial acetic acid (GAA) is by petrochemical routes, primarily methanol carbonylation. GAA is an intermediate in the production of plastics, textiles, dyes, and paints. GAA production from biomass might be an economically viable and sustainable alternative to petroleum-derived routes. Separation of acetic acid from water is a major expense and requires considerable energy. This study evaluates and compares the technical and economic feasibility of GAA production via bioconversion using either ethyl acetate or alamine in diisobutylkerosene (DIBK) as organic solvents for purification. Models of a GAA biorefinery with a production of 120,650 tons/year were simulated in Aspen software. This biorefinery follows the path of pretreatment, enzymatic hydrolysis, acetogen fermentation, and acid purification. Estimated capital costs for different scenarios ranged from USD 186 to 245 million. Recovery of GGA using alamine/DIBK was a more economical process and consumed 64% less energy, due to lower steam demand in the recovery distillation columns. The estimated average minimum selling prices of GGA were USD 756 and 877/ton for alamine/DIBK and ethyl acetate scenarios, respectively. This work establishes a feasible and sustainable approach to produce GGA from poplar biomass via fermentation.
Fabrication of Carbon-Like, π-Conjugated Organic Layer on a Nano-Porous Silica Surface
Authors: Noguchi Hiroki , Sultana Marzia , Hano Nanami , Kuwahara Yutaka , Takafuji Makoto , Nagaoka Shoji , Qiu Hongdeng , Ihara Hirotaka
Published: September 2020

This paper presents a new type of black organic material-porous silica composite providing an extremely highly selective adsorption surface. This black composite was prepared by lamination on nano-sized pores with a carbon-like, π-extended structure, which can be converted via the on-site polymerization of 1,5-dihydroxynaphthalene with a triazinane derivative and a thermally induced condensation reaction with denitrification. This bottom-up fabrication method on porous materials had the great advantage of maintaining the pore characteristics of a raw porous material, but also the resultant black surface exhibited an extremely high molecular-shape selectivity; for example, that for trans- and cis-stilbenes reached 14.0 with the black layer-laminated porous silica, whereas it was below 1.2 with simple hydrophobized silica.
Synthesis of the ZnTiO3/TiO2 Nanocomposite Supported in Ecuadorian Clays for the Adsorption and Photocatalytic Removal of Methylene Blue Dye
Authors: Jaramillo-Fierro Ximena , González Silvia , Jaramillo Hipatia Alvarado , Medina Francesc
Published: September 2020

Currently, the study of semiconductor materials is very promising for the photocatalytic remediation of hazardous organic substances present in the air and water. Various semiconductors have been investigated in this interesting photo-assisted methodology, among them metal oxides such as ZnO, TiO2 and their derivatives. In this study, ZnTiO3/TiO2 was synthesized by the sol-gel method using Ti(OC3H7)4 and Zn(CH3COO)2 · 2H2O as reagents. The role of several conditions such as synthesis temperature and TiO2:ZnO proportion on the morphology and purity of compounds obtained was studied, and the suitable conditions for the synthesis of photocatalysts were determined. Various techniques were used to conduct a systematic investigation on the structural, morphological, and photocatalytic properties of ZnTiO3/TiO2. Scanning Electron Microscopy (SEM) images show that ZnTiO3/TiO2 have a typical particle size of approximately 100 nm with a quasi-spherical shape. The adsorption and photocatalytic activity were investigated by the decolorization of Methylene Blue (MB) as an organic contaminant under UV irradiation both in TiO2 and ZnTiO3/TiO2 supported over some Ecuadorian clays. The materials evaluated were prepared in the shape of 0.2 cm (diameter) and 1.0 cm (length) cylindrical extrudates. The degradation percentage of MB obtained was 85% approximately after 150 min of irradiation. The results obtained allow us to conclude that these synthesized materials can be used as adsorbents and photocatalysts.
Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review
Authors: Watanabe Mikiko , Risi Renata , Masi Davide , Caputi Alessandra , Balena Angela , Rossini Giovanni , Tuccinardi Dario , Mariani Stefania , Basciani Sabrina , Manfrini Silvia , Gnessi Lucio , Lubrano Carla
Published: September 2020

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.