bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusion Potential of Human Osteoclasts In Vitro Reflects Age, Menopause, and In Vivo Bone Resorption Levels of Their Donors—A Possible Involvement of DC-STAMP
Authors: Møller Anaïs M. J. , Delaissé Jean-Marie , Olesen Jacob B. , Canto Luisa M. , Rogatto Silvia R. , Madsen Jonna S. , Søe Kent
Published: September 2020

It is well established that multinucleation is central for osteoclastic bone resorption. However, our knowledge on the mechanisms regulating how many nuclei an osteoclast will have is limited. The objective of this study was to investigate donor-related variations in the fusion potential of in vitro-generated osteoclasts. Therefore, CD14+ monocytes were isolated from 49 healthy female donors. Donor demographics were compared to the in vivo bone biomarker levels and their monocytes’ ability to differentiate into osteoclasts, showing that: (1) C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels increase with age, (2) the number of nuclei per osteoclast in vitro increases with age, and (3) there is a positive correlation between the number of nuclei per osteoclast in vitro and CTX levels in vivo. Furthermore, the expression levels of the gene encoding dendritic cell-specific transmembrane protein (DCSTAMP) of osteoclasts in vitro correlated positively with the number of nuclei per osteoclast, CTX levels in vivo, and donor age. Our results furthermore suggest that these changes in gene expression may be mediated through age-related changes in DNA methylation levels. We conclude that both intrinsic factors and age-induced increase in fusion potential of osteoclasts could be contributing factors for the enhanced bone resorption in vivo, possibly caused by increased expression levels of DCSTAMP.
Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies
Authors: Lachén-Montes Mercedes , Mendizuri Naroa , Schvartz Domitille , Fernández-Irigoyen Joaquín , Sánchez Jean Charles , Santamaría Enrique
Published: September 2020

Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB–olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB.
Evidence of Skin Barrier Damage by Cyclic Siloxanes (Silicones)—Using Digital Holographic Microscopy
Authors: Mojsiewicz-Pieńkowska Krystyna , Stachowska Ewa , Krenczkowska Dominika , Bazar Dagmara , Meijer Frans
Published: September 2020

Cyclic siloxanes (D4, D5, D6) are widely used in skin products. They improve skin sensory properties and alleviate dry skin, but there is still one report (published 2019), which regards their effects on the destruction of the skin barrier, by using fluorescence microscopy and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). A new skin-imaging technique, digital holographic microscopy (DHM), was used for the first time to investigate the impact of D4, D5, and D6 on the skin barrier. We observed irreversible damage of the stratum corneum due to the interaction with cyclic siloxanes. These substances changed: (a) the first level of the skin barrier through destabilization of the intercellular lipid lamellae and destruction of the corneocyte structure (measured with axial nanometer resolution), (b) the second level by collapse of not only corneocytes but also of a significant part of the clusters, leading to the loss of the stratum corneum integrity and formation of the lacunae, (c) the third level as an effect of the change in the surface geometrical topography of the stratum corneum and disruption of the integrity of this skin layer, measured with lateral micrometer resolution. DHM allowed also to identify an important pathway for substances to penetrate into the skin through canyons surrounding the clusters. Our investigations provide advanced information for understanding the mechanisms by which various substances pass the skin barrier, including uncontrolled diffusion into the skin.
Local and Systemic Changes in Photosynthetic Parameters and Antioxidant Activity in Cucumber Challenged with Pseudomonas syringae pv lachrymans
Authors: Kopczewski Tomasz , Kuźniak Elżbieta , Kornaś Andrzej , Rut Grzegorz , Nosek Michał , Ciereszko Iwona , Szczepaniak Lech
Published: September 2020

We studied changes in gas exchange, photochemical activity and the antioxidant system in cucumber leaves locally infected with Pseudomonas syringae pv lachrymans and in uninfected systemic ones. Infection-induced declined net photosynthesis rate and the related changes in transpiration rate, the intracellular CO2 concentration, and prolonged reduction in maximal PSII quantum yield (Fv/Fm), accompanied by an increase in non-photochemical quenching (NPQ), were observed only in the infected leaves, along with full disease symptom development. Infection severely affected the ROS/redox homeostasis at the cellular level and in chloroplasts. Superoxide dismutase, ascorbate, and tocopherol were preferentially induced at the early stage of pathogenesis, whereas catalase, glutathione, and the ascorbate–glutathione cycle enzymes were activated later. Systemic leaves retained their net photosynthesis rate and the changes in the antioxidant system were partly like those in the infected leaves, although they occurred later and were less intense. Re-balancing of ascorbate and glutathione in systemic leaves generated a specific redox signature in chloroplasts. We suggest that it could be a regulatory element playing a role in integrating photosynthesis and redox regulation of stress, aimed at increasing the defense capacity and maintaining the growth of the infected plant.
The Metabolic Reprogramming Induced by Sub-Optimal Nutritional and Light Inputs in Soilless Cultivated Green and Red Butterhead Lettuce
Authors: Miras-Moreno Begoña , Corrado Giandomenico , Zhang Leilei , Senizza Biancamaria , Righetti Laura , Bruni Renato , El-Nakhel Christophe , Sifola Maria Isabella , Pannico Antonio , Pascale Stefania De , Rouphael Youssef , Lucini Luigi
Published: September 2020

Sub-optimal growing conditions have a major effect on plants; therefore, large efforts are devoted to maximizing the availability of agricultural inputs to crops. To increase the sustainable use of non-renewable inputs, attention is currently given to the study of plants under non-optimal conditions. In this work, we investigated the impact of sub-optimal macrocations availability and light intensity in two lettuce varieties that differ for the accumulation of secondary metabolites (i.e., ‘Red Salanova’ and ‘Green Salanova’). Photosynthesis-related measurements and untargeted metabolomics were used to identify responses and pathways involved in stress resilience. The pigmented (‘Red’) and the non-pigmented (‘Green Salanova’) lettuce exhibited distinctive responses to sub-optimal conditions. The cultivar specific metabolomic signatures comprised a broad modulation of metabolism, including secondary metabolites, phytohormones, and membrane lipids signaling cascade. Several stress-related metabolites were altered by either treatment, including polyamines (and other nitrogen-containing compounds), phenylpropanoids, and lipids. The metabolomics and physiological response to macrocations availability and light intensity also implies that the effects of low-input sustainable farming systems should be evaluated considering a range of cultivar-specific positive and disadvantageous metabolic effects in addition to yield and other socio-economic parameters.
Antimicrobial and Amyloidogenic Activity of Peptides Synthesized on the Basis of the Ribosomal S1 Protein from Thermus Thermophilus
Authors: Kurpe Stanislav , Grishin Sergei , Surin Alexey , Selivanova Olga , Fadeev Roman , Dzhus Ulyana , Gorbunova Elena , Mustaeva Leila , Azev Vyacheslav , Galzitskaya Oxana
Published: September 2020

Controlling the aggregation of vital bacterial proteins could be one of the new research directions and form the basis for the search and development of antibacterial drugs with targeted action. Such approach may be considered as an alternative one to antibiotics. Amyloidogenic regions can, like antibacterial peptides, interact with the “parent” protein, for example, ribosomal S1 protein (specific only for bacteria), and interfere with its functioning. The aim of the work was to search for peptides based on the ribosomal S1 protein from T. thermophilus, exhibiting both aggregation and antibacterial properties. The biological system of the response of Gram-negative bacteria T. thermophilus to the action of peptides was characterized. Among the seven studied peptides, designed based on the S1 protein sequence, the R23I (modified by the addition of HIV transcription factor fragment for bacterial cell penetration), R23T (modified), and V10I (unmodified) peptides have biological activity that inhibits the growth of T. thermophilus cells, that is, they have antimicrobial activity. But, only the R23I peptide had the most pronounced activity comparable with the commercial antibiotics. We have compared the proteome of peptide-treated and intact T. thermophilus cells. These important data indicate a decrease in the level of energy metabolism and anabolic processes, including the processes of biosynthesis of proteins and nucleic acids. Under the action of 20 and 50 μg/mL R23I, a decrease in the number of proteins in T. thermophilus cells was observed and S1 ribosomal protein was absent. The obtained results are important for understanding the mechanism of amyloidogenic peptides with antimicrobial activity and can be used to develop new and improved analogues.
Siloxanes—Versatile Materials for Surface Functionalisation and Graft Copolymers
Authors: Glosz Karolina , Stolarczyk Agnieszka , Jarosz Tomasz
Published: September 2020

Siloxanes are adaptable species that have found extensive applications as versatile materials for functionalising various surfaces and as building blocks for polymers and hybrid organic-inorganic systems. The primary goal of this review is to report on and briefly explain the most relevant recent developments related to siloxanes and their applications, particularly regarding surface modification and the synthesis of graft copolymers bearing siloxane or polysiloxane segments. The key strategies for both functionalisation and synthesis of siloxane-bearing polymers are highlighted, and the various trends in the development of siloxane-based materials and the intended directions of their applications are explored.
Human Cell Modeling for Cardiovascular Diseases
Authors: Lippi Melania , Stadiotti Ilaria , Pompilio Giulio , Sommariva Elena
Published: September 2020

The availability of appropriate and reliable in vitro cell models recapitulating human cardiovascular diseases has been the aim of numerous researchers, in order to retrace pathologic phenotypes, elucidate molecular mechanisms, and discover therapies using simple and reproducible techniques. In the past years, several human cell types have been utilized for these goals, including heterologous systems, cardiovascular and non-cardiovascular primary cells, and embryonic stem cells. The introduction of induced pluripotent stem cells and their differentiation potential brought new prospects for large-scale cardiovascular experiments, bypassing ethical concerns of embryonic stem cells and providing an advanced tool for disease modeling, diagnosis, and therapy. Each model has its advantages and disadvantages in terms of accessibility, maintenance, throughput, physiological relevance, recapitulation of the disease. A higher level of complexity in diseases modeling has been achieved with multicellular co-cultures. Furthermore, the important progresses reached by bioengineering during the last years, together with the opportunities given by pluripotent stem cells, have allowed the generation of increasingly advanced in vitro three-dimensional tissue-like constructs mimicking in vivo physiology. This review provides an overview of the main cell models used in cardiovascular research, highlighting the pros and cons of each, and describing examples of practical applications in disease modeling.
Decreased Urinary Levels of SIRT1 as Non-Invasive Biomarker of Early Renal Damage in Hypertension
Authors: Martinez-Arroyo Olga , Ortega Ana , Galera Miriam , Solaz Elena , Martinez-Hervas Sergio , Redon Josep , Cortes Raquel
Published: September 2020

Sirtuins have become important players in renal damage in hypertension and diabetes, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the levels of sirtuin1 (SIRT1), and two miRNAs that regulate SIRT1 expression in hypertensive patients with incipient renal damage with and without diabetes. We quantified urinary SIRT1 and claudin 1 (CLDN1) mRNA and miR34-a and miR-200a levels by quantitative real-time polymerase chain reaction (RT-qPCR) from patients and in cultured podocytes treated with high glucose and angiotensin II. Western blot and fluorescence analyses were also performed. We found decreased SIRT1 levels in patients with increased urinary albumin excretion (UAE), the lowest with diabetes presence, and a strong association with UAE, discriminating incipient renal damage. In vitro experiments also showed SIRT1 overall decreases in podocyte cultures under treatment conditions. In urine samples, miR-34a was reduced and miR-200a increased, both related to UAE levels. However, both miRNAs were generally increased in podocyte cultures under high glucose and angiotensin-II treatment. These results show a significant urinary SIRT1 decrease in albuminuric hypertensive patients, strongly associated with albuminuria, suggesting that SIRT1 could be a potential and non-invasive method to assess incipient renal damage in hypertensive patients.
Chemoenzymatic Synthesis of the New 3-((2,3-Diacetoxypropanoyl)oxy)propane-1,2-diyl Diacetate Using Immobilized Lipase B from Candida antarctica and Pyridinium Chlorochromate as an Oxidizing Agent
Authors: Plata Esteban , Ruiz Mónica , Ruiz Jennifer , Ortiz Claudia , Castillo John J. , Fernández-Lafuente Roberto
Published: September 2020

To exploit the hydrolytic activity and high selectivity of immobilized lipase B from Candida antarctica on octyl agarose (CALB-OC) in the hydrolysis of triacetin and also to produce new value-added compounds from glycerol, this work describes a chemoenzymatic methodology for the synthesis of the new dimeric glycerol ester 3-((2,3-diacetoxypropanoyl)oxy)propane-1,2-diyl diacetate. According to this approach, triacetin was regioselectively hydrolyzed to 1,2-diacetin with CALB-OC. The diglyceride product was subsequently oxidized with pyridinium chlorochromate (PCC) and a dimeric ester was isolated as the only product. It was found that the medium acidity during the PCC treatment and a high 1,2-diacetin concentration favored the formation of the ester. The synthesized compounds were characterized using IR, MS, HR-MS, and NMR techniques. The obtained dimeric ester was evaluated at 100 ppm against seven bacterial strains and two Candida species to identify its antimicrobial activity. The compound has no inhibitory activity against the bacterial strains used but decreased C. albicans and C. parapsilosis growth by 49% and 68%, respectively. Hemolytic activity was evaluated, and the results obtained support the use of the dimeric ester to control C. albicans and C. parapsilosis growth in non-intravenous applications because the compound shows hemolytic activity.
New Insights of Oral Colonic Drug Delivery Systems for Inflammatory Bowel Disease Therapy
Authors: Teruel Adrian H. , Gonzalez-Alvarez Isabel , Bermejo Marival , Merino Virginia , Marcos Maria Dolores , Sancenon Felix , Gonzalez-Alvarez Marta , Martinez-Mañez Ramon
Published: September 2020

Colonic Drug Delivery Systems (CDDS) are especially advantageous for local treatment of inflammatory bowel diseases (IBD). Site-targeted drug release allows to obtain a high drug concentration in injured tissues and less systemic adverse effects, as consequence of less/null drug absorption in small intestine. This review focused on the reported contributions in the last four years to improve the effectiveness of treatments of inflammatory bowel diseases. The work concludes that there has been an increase in the development of CDDS in which pH, specific enzymes, reactive oxygen species (ROS), or a combination of all of these triggers the release. These delivery systems demonstrated a therapeutic improvement with fewer adverse effects. Future perspectives to the treatment of this disease include the elucidation of molecular basis of IBD diseases in order to design more specific treatments, and the performance of more in vivo assays to validate the specificity and stability of the obtained systems.
Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate
Authors: Vidmar Golja Maša , Šmid Alenka , Karas Kuželički Nataša , Trontelj Jurij , Geršak Ksenija , Mlinarič-Raščan Irena
Published: September 2020

Adequate levels of folates are essential for homeostasis of the organism, prevention of congenital malformations, and the salvage of predisposed disease states. They depend on genetic predisposition, and therefore, a pharmacogenetic approach to individualized supplementation or therapeutic intervention is necessary for an optimal outcome. The role of folates in vital cell processes was investigated by translational pharmacogenetics employing lymphoblastoid cell lines (LCLs). Depriving cells of folates led to reversible S-phase arrest. Since 5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in the biosynthesis of an active folate form, we evaluated the relevance of polymorphisms in the MTHFR gene on intracellular levels of bioactive metabolite, the 5-methyltetrahydrofolate (5-Me-THF). LCLs (n = 35) were divided into low- and normal-MTHFR activity groups based on their genotype. They were cultured in the presence of folic acid (FA) or 5-Me-THF. Based on the cells’ metabolic activity and intracellular 5-Me-THF levels, we conclude supplementation of FA is sufficient to maintain adequate folate level in the normal MTHFR activity group, while low MTHFR activity cells require 5-Me-THF to overcome the metabolic defects caused by polymorphisms in their MTHFR genes. This finding was supported by the determination of intracellular levels of 5-Me-THF in cell lysates by LC-MS/MS. FA supplementation resulted in a 2.5-fold increase in 5-Me-THF in cells with normal MTHFR activity, but there was no increase after FA supplementation in low MTHFR activity cells. However, when LCLs were exposed to 5-Me-THF, a 10-fold increase in intracellular levels of this metabolite was determined. These findings indicate that patients undergoing folate supplementation to counteract anti-folate therapies, or patients with increased folate demand, would benefit from pharmacogenetics-based therapy choices.
Metformin Attenuates Osteoporosis in Diabetic Patients with Carcinoma in Situ: A Nationwide, Retrospective, Matched-Cohort Study in Taiwan
Authors: Lu Chieh-Hua , Chung Chi-Hsiang , Kuo Feng-Chih , Chen Kuan-Chan , Chang Chia-Hao , Kuo Chih-Chun , Lee Chien-Hsing , Su Sheng-Chiang , Liu Jhih-Syuan , Lin Fu-Huang , Tsao Chang-Huei , Hsieh Po-Shiuan , Hung Yi-Jen , Hsieh Chang-Hsun , Chien Wu-Chien
Published: September 2020

Patients with diabetes are at increased risk of cancer development and osteoporosis. Metformin is an effective agent for diabetes management. Epidemiological studies have identified an association between metformin use and cancer prevention. This article outlines the potential for metformin to attenuate the rate of osteoporosis in diabetic patients with carcinoma in situ (CIS). From the National Health Insurance Research Database of Taiwan, 7827 patients with diabetes with CIS who were receiving metformin therapy were selected, along with 23,481 patients as 1:3 sex-, age- and index year-matched controls, who were not receiving metformin therapy. A Cox proportional hazard analysis was used to compare the rate of osteoporosis during an average of 15-year follow-up. Of the subjects who were enrolled, 801 (2.56%) had osteoporosis, including 168 from the metformin group (2.15%) and 633 from the without metformin group (2.70%). The metformin group presented a lower rate of osteoporosis at the end of follow-up (p = 0.009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691–0.972, p = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy.
Clinical Impact of Corrections to Infliximab and Adalimumab Monitoring Results with the Homogeneous Mobility Shift Assay
Authors: Papamichael Konstantinos , Thomas Valerio J. , Banty Andrea , Clarke William T. , Germansky Katharine A. , Flier Sarah N. , Feuerstein Joseph D. , Melmed Gil Y. , Cheifetz Adam S.
Published: September 2020

An upward drift for both infliximab and adalimumab concentrations measured by the homogenous mobility shift assay (HMSA) was previously reported. We aimed to investigate the impact of this drift on clinical care of patients with inflammatory bowel disease. This was a retrospective, multicenter study. Providers reviewed the individual patient data and drug concentrations before and after the laboratory corrections and then documented whether a different clinical decision would have been made had the corrected drug concentration been originally reported. A multivariable Cox proportional hazards regression analysis was performed to investigate the association of a documented treatment change with treatment failure, defined as drug discontinuation for primary nonresponse, loss of response, or serious adverse event, adjusting for confounding factors. The study population consisted of 479 patients (infliximab, n = 219; adalimumab, n = 260). Upon review, 14.9% (71/479) patients would have had a different treatment decision made had the corrected drug concentration been initially reported. After a median follow-up of 10.6 months, 25.7% of patients (123/479) had treatment failure. A theoretical different clinical decision based on the corrected drug concentrations was not associated with treatment failure (adjusted hazard ratio (HR): 1.452; 95% confidence interval (CI): 0.805–2.618; p = 0.216), which was consistent for both infliximab (adjusted HR: 1.977; 95% CI: 0.695–5.627; p = 0.201) and adalimumab (adjusted HR: 1.484; 95% CI: 0.721–3.054; p = 0.284). The drift in infliximab and adalimumab concentrations in the HMSA assay affected treatment decisions in 15% of cases. However, this discrepancy was not associated with a higher cumulative probability for treatment failure.
Upper Respiratory Tract Microbiome and Otitis Media Intertalk: Lessons from the Literature
Authors: Folino Francesco , Ruggiero Luca , Capaccio Pasquale , Coro Ilaria , Aliberti Stefano , Drago Lorenzo , Marchisio Paola , Torretta Sara
Published: September 2020

Otitis media (OM) is one of the most common diseases occurring during childhood. Microbiological investigations concerning this topic have been primarily focused on the four classical otopathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes) mainly because most of the studies have been conducted with culture-dependent methods. In recent years, the introduction of culture-independent techniques has allowed high-throughput investigation of entire bacterial communities, leading to a better comprehension of the role of resident flora in health and disease. The upper respiratory tract (URT) is a region of major interest in otitis media pathogenesis, as it could serve as a source of pathogens for the middle ear (ME). Studies conducted with culture-independent methods in the URT and ME have provided novel insights on the pathogenesis of middle ear diseases through the identification of both possible new causative agents and of potential protective bacteria, showing that imbalances in bacterial communities could influence the natural history of otitis media in children. The aim of this review is to examine available evidence in microbiome research and otitis media in the pediatric age, with a focus on its different phenotypes: acute otitis media, otitis media with effusion and chronic suppurative otitis media.
Modeling of the Evolution of the Microstructure and the Hardness Penetration Depth for a Hypoeutectoid Steel Processed by Grind-Hardening
Authors: Guo Yu , Liu Minghe , Yin Mingang , Yan Yutao
Published: September 2020

Grind-hardening processing is an emerging approach that combines the grinding and surface quenching process. During the process, the hardened layer—mainly martensite—is produced on the surface of the workpiece to achieve the purpose of surface strengthening. Above all, the surface temperature field of the hypoeutectoid-1045 steel workpiece was determined by finite element method for fully revealing the formation mechanism of the hardened layer. Further, the cellular automata approach was applied to dynamically simulate the transformation of both austenitization and martensitization from the initial microstructure. The hardness penetration depth was also predicted. Finally, a grind-hardening experiment was conducted to assess the theoretical study. Results showed that a combination of the finite element method and the cellular automata approach can effectively simulate the microstructure transformation of hardened layer. The microstructure and the hardness penetration depth were affected by the maximum grinding temperature and the heating rate. Research on the influence of grinding parameters showed that the hardness penetration depth increased as the depth of the wheel cut and feeding speed increased. Experiments revealed that the difference between predicted value and experimental value of the hardness penetration depth varied between 2.83% and 7.31%, which confirmed the effectiveness of the predicted model.
In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors
Authors: Zulkipli Ninie Nadia , Zakaria Rahimah , Long Idris , Abdullah Siti Fadilah , Muhammad Erma Fatiha , Wahab Habibah A. , Sasongko Teguh Haryo
Published: September 2020

Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
Telodendrimers: Promising Architectural Polymers for Drug Delivery
Authors: Mejlsøe Søren , Kakkar Ashok
Published: September 2020

Architectural complexity has played a key role in enhancing the efficacy of nanocarriers for a variety of applications, including those in the biomedical field. With the continued evolution in designing macromolecules-based nanoparticles for drug delivery, the combination approach of using important features of linear polymers with dendrimers has offered an advantageous and viable platform. Such nanostructures, which are commonly referred to as telodendrimers, are hybrids of linear polymers covalently linked with different dendrimer generations and backbones. There is considerable variety in selection from widely studied linear polymers and dendrimers, which can help tune the overall composition of the resulting hybrid structures. This review highlights the advances in articulating syntheses of these macromolecules, and the contributions these are making in facilitating therapeutic administration. Limited progress has been made in the design and synthesis of these hybrid macromolecules, and it is through an understanding of their physicochemical properties and aqueous self-assembly that one can expect to fully exploit their potential in drug delivery.
Nanocrystalline Antiferromagnetic High-κ Dielectric Sr2NiMO6 (M = Te, W) with Double Perovskite Structure Type
Authors: Bijelić Jelena , Tatar Dalibor , Hajra Sugato , Sahu Manisha , Kim Sang Jae , Jagličić Zvonko , Djerdj Igor
Published: September 2020

Double perovskites have been extensively studied in materials chemistry due to their excellent properties and novel features attributed to the coexistence of ferro/ferri/antiferro-magnetic ground state and semiconductor band gap within the same material. Double perovskites with Sr2NiMO6 (M = Te, W) structure type have been synthesized using simple, non-toxic and costless aqueous citrate sol-gel route. The reaction yielded phase-pure nanocrystalline powders of two compounds: Sr2NiWO6 (SNWO) and Sr2NiTeO6 (SNTO). According to the Rietveld refinement of powder X-ray diffraction data at room temperature, Sr2NiWO6 is tetragonal (I4/m) and Sr2NiTeO6 is monoclinic (C12/m1), with average crystallite sizes of 49 and 77 nm, respectively. Structural studies have been additionally performed by Raman spectroscopy revealing optical phonons typical for vibrations of Te6+/W6+O6 octahedra. Both SNTO and SNWO possess high values of dielectric constants (341 and 308, respectively) with low dielectric loss (0.06 for SNWO) at a frequency of 1 kHz. These values decrease exponentially with the increase of frequency to 1000 kHz, with the dielectric constant being around 260 for both compounds and dielectric loss being 0.01 for SNWO and 0.04 for SNTO. The Nyquist plot for both samples confirms the non-Debye type of relaxation behavior and the dominance of shorter-range movement of charge carriers. Magnetic studies of both compounds revealed antiferromagnetic behavior, with Néel temperature (TN) being 57 K for SNWO and 35 K for SNTO.
Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice
Authors: Guo Sen , Zhao Haoan , Ma Zhongxiao , Zhang Shanshan , Li Mingrou , Zheng Zhaojing , Ren Xiameng , Ho Chi-Tang , Bai Naisheng
Published: September 2020

Previously we conducted a phytochemical study on the seeds of Fraxinus excelsior and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of Fraxinus mandshurica seeds have not been studied. In the present study, we investigated the secoiridoid compounds in F. mandshurica seed extract (FM) using column chromatography, 1H-NMR, 13C-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect of FM on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from FM and identified. The total content of secoiridoids in FM reached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 μM. After obese mice were administrated with FM at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, FM could attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice. FM could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes, Bacteroidia, S24-7 and Allobaculum), and reducing the proportion of obesogenic gut microbiota (Firmicutes and Dorea). This study suggests that F. mandshurica seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.
Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis
Authors: Riezk Alaa , Van Bocxlaer Katrien , Yardley Vanessa , Murdan Sudaxshina , Croft Simon L.
Published: September 2020

Chitosan nanoparticles have gained attention as drug delivery systems (DDS) in the medical field as they are both biodegradable and biocompatible with reported antimicrobial and anti-leishmanial activities. We investigated the application of chitosan nanoparticles as a DDS for the treatment of cutaneous leishmaniasis (CL) by preparing two types of chitosan nanoparticles: positively charged with tripolyphosphate sodium (TPP) and negatively charged with dextran sulphate. Amphotericin B (AmB) was incorporated into these nanoparticles. Both types of AmB-loaded nanoparticles demonstrated in vitro activity against Leishmania major intracellular amastigotes, with similar activity to unencapsulated AmB, but with a significant lower toxicity to KB-cells and red blood cells. In murine models of CL caused by L. major, intravenous administration of AmB-loaded chitosan-TPP nanoparticles (Size = 69 ± 8 nm, Zeta potential = 25.5 ± 1 mV, 5 mg/kg/for 10 days on alternate days) showed a significantly higher efficacy than AmBisome® (10 mg/kg/for 10 days on alternate days) in terms of reduction of lesion size and parasite load (measured by both bioluminescence and qPCR). Poor drug permeation into and through mouse skin, using Franz diffusion cells, showed that AmB-loaded chitosan nanoparticles are not appropriate candidates for topical treatment of CL.
Quercitrin Stimulates Hair Growth with Enhanced Expression of Growth Factors via Activation of MAPK/CREB Signaling Pathway
Authors: Kim Jaeyoon , Kim Soon Re , Choi Yun-Ho , Shin Jae young , Kim Chang Deok , Kang Nae-Gyu , Park Byung Cheol , Lee Sanghwa
Published: September 2020

The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors—such as bFGF, KGF, PDGF-AA, and VEGF—were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway.
Comprehensive Metabolome Analysis of Fermented Aqueous Extracts of Viscum album L. by Liquid Chromatography−High Resolution Tandem Mass Spectrometry
Authors: Peñaloza Evelyn , Holandino Carla , Scherr Claudia , Araujo Paula I. P. de , Borges Ricardo M. , Urech Konrad , Baumgartner Stephan , Garrett Rafael
Published: September 2020

Fermented aqueous extracts of Viscum album L. are widely used for cancer treatment in complementary medicine. The high molecular weight compounds viscotoxins and lectins are considered to be the main active substances in the extracts. However, a vast number of small molecules (≤1500 Da) is also expected to be present, and few studies have investigated their identities. In this study, a comprehensive metabolome analysis of samples of fermented aqueous extracts of V. album from two host tree species (Malus domestica and Pinus sylvestris), both prepared by two pharmaceutical manufacturing processes, was performed by liquid chromatography−high resolution tandem mass spectrometry (LC-HRMS/MS). A total of 212 metabolites were putatively annotated, including primary metabolites (e.g., amino acids, organic acids, etc.) and secondary metabolites (mostly phenolic compounds). A clear separation between V. album samples according to the host tree species, but not due to manufacturing processes, was observed by principal component analysis. The biomarkers responsible for this discrimination were assessed by partial least squares−discriminant analysis. Because V. album extracts from different host trees have different clinical applications, the present work highlights the possibility of characterizing the metabolome for identification and traceability of V. album fermented aqueous extracts.
Semi-Synthetic Approach Leading to 8-Prenylnaringenin and 6-Prenylnaringenin: Optimization of the Microwave-Assisted Demethylation of Xanthohumol Using Design of Experiments
Authors: Urmann Corinna , Riepl Herbert
Published: September 2020

The isomers 8-prenylnaringenin and 6-prenylnaringenin, both secondary metabolites occurring in hops, show interesting biological effects, like estrogen-like, cytotoxic, or neuro regenerative activities. Accordingly, abundant sources for this special flavonoids are needed. Extraction is not recommended due to the very low amounts present in plants and different synthesis approaches are characterized by modest yields, multiple steps, the use of expensive chemicals, or an elaborate synthesis. An easy synthesis strategy is the demethylation of xanthohumol, which is available due to hop extraction industry, using lithium chloride and dimethylformamide, but byproducts and low yield did not make this feasible until now. In this study, the demethylation of xanthohumol to 8-prenylnaringenin and 6-prenylnaringenin is described the first time and this reaction was optimized using Design of Experiment and microwave irradiation. With the optimized conditions—temperature 198 °C, 55 eq. lithium chloride, and a reaction time of 9 min, a final yield of 76% of both prenylated flavonoids is reached.
Methods of Purification and Application Procedures of Alpha1 Antitrypsin: A Long-Lasting History
Authors: Viglio Simona , Iadarola Paolo , D’Amato Maura , Stolk Jan
Published: September 2020

The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) and other proteases released by neutrophils during an inflammatory state. The lack of this inhibitor in human serum is responsible for the onset of alpha1-antitrypsin deficiency (AATD), which is a severe genetic disorder that affects lungs in adults and for which there is currently no cure. Being used, under special circumstances, as a medical treatment of AATD in the so-called “replacement” therapy (consisting in the intravenous infusion of the missing protein), AAT is a molecule with a lot of therapeutic importance. For this reason, interest in AAT purification from human plasma or its production in a recombinant version has grown considerably in recent years. This article retraces all technological advances that allowed the manufacturers to move from a few micrograms of partially purified AAT to several grams of highly purified protein. Moreover, the chronic augmentation and maintenance therapy in individuals with emphysema due to congenital AAT deficiency (current applications in the clinical setting) is also presented.
Thermal-Oxidation Stability of Soybean Germ Phytosterols in Different Lipid Matrixes
Authors: Chen Jingnan , Li Dami , Tang Guiyun , Zhou Jinfen , Liu Wei , Bi Yanlan
Published: September 2020

The stability of soybean germ phytosterols (SGPs) in different lipid matrixes, including soybean germ oil, olive oil, and lard, was studied at 120, 150, and 180 °C. Results on the loss rate demonstrated that SGPs were most stable in olive oil, followed by soybean germ oil, and lard in a decreasing order. It is most likely that unsaturated fatty acids could oxidize first, compete with consumption of oxygen, and then spare phytosterols from oxidation. The oxidation products of SGPS in non-oil and oil systems were also quantified. The results demonstrated that at relatively lower temperatures (120 and 150 °C), SGPs’ oxidation products were produced the most in the non-oil system, followed by lard, soybean germ oil, and olive oil. This was consistent with the loss rate pattern of SGPs. At a relatively higher temperature of 180 °C, the formation of SGPs’ oxidation products in soybean germ oil was quantitatively the same as that in lard, implying that the temperature became a dominative factor rather than the content of unsaturated fatty acids of lipid matrixes in the oxidation of SGPs.
Radio Frequency IDentification for Meat Supply-Chain Digitalisation
Authors: Barge Paolo , Biglia Alessandro , Comba Lorenzo , Ricauda Aimonino Davide , Tortia Cristina , Gay Paolo
Published: September 2020

Digitalised supply-chain traceability systems can offer wide prospects both for improving safety as well as enhancing perceived quality. However, the coupling between physical goods and information is often difficult for agri-food items. A solution could be the use of RFID (Radio Frequency IDentification) systems. Due to its wide reading range, Ultra-High Frequency (UHF) technology is already widely used in logistics and warehousing, mostly for the identification of batches of items. A growing interest is also emerging in Near Field Communication (NFC), as several smartphones embed an integrated NFC antenna. This paper deals with the automatic identification of meat products at item level, proposing and evaluating the adoption of different RFID technologies. Different UHF and NFC solutions are proposed, which benchmark tag performances in different configurations, including four meat types (fatty beef, lean beef, chicken and pork), by using a specifically designed test bench. As avoiding the application of two different tags could be advantageous, dual frequency devices (UHF and NFC) are also considered. Significant differences in tag performances, which also depend on meat type and packaging, are highlighted. The paper highlights that tag positioning should consider the geometry of the packaging and the relative positioning of tag, meat and reader antenna.
Robust Estimation of Carbon Monoxide Measurements
Authors: Hernandez Wilmar , Mendez Alfredo
Published: September 2020

This paper presents a robust analysis of carbon monoxide (CO) concentration measurements conducted at the Belisario air-quality monitoring station (Quito, Ecuador). For the analysis, the data collected from 1 January 2008 to 31 December 2019 were considered. Additionally, each of the twelve years analyzed was considered as a random variable, and robust location and scale estimators were used to estimate the central tendency and dispersion of the data. Furthermore, classic, nonparametric, bootstrap, and robust confidence intervals were used to group the variables into categories. Then, differences between categories were quantified using confidence intervals and it was shown that the trend of CO concentration at the Belisario station in the last twelve years is downward. The latter was proven with the precision provided by both nonparametric and robust statistical methods. The results of the research work robustly proved that the CO concentration at Belisario station in the last twelve years is not considered a health risk, according to the criteria established by the Quito Air Quality Index.
A Novel Dynamic Three-Level Tracking Controller for Mobile Robots Considering Actuators and Power Stage Subsystems: Experimental Assessment
Authors: García-Sánchez José Rafael , Tavera-Mosqueda Salvador , Silva-Ortigoza Ramón , Hernández-Guzmán Victor Manuel , Marciano-Melchor Magdalena , Rubio José de Jesús , Ponce-Silva Mario , Hernández-Bolaños Miguel , Martínez-Martínez Jesús
Published: September 2020

In order to solve the trajectory tracking task in a wheeled mobile robot (WMR), a dynamic three-level controller is presented in this paper. The controller considers the mechanical structure, actuators, and power stage subsystems. Such a controller is designed as follows: At the high level is a dynamic control for the WMR (differential drive type). At the medium level is a PI current control for the actuators (DC motors). Lastly, at the low level is a differential flatness-based control for the power stage (DC/DC Buck power converters). The feasibility, robustness, and performance in closed-loop of the proposed controller are validated on a DDWMR prototype through Matlab-Simulink, the real-time interface ControlDesk, and a DS1104 board. The obtained results are experimentally assessed with a hierarchical tracking controller, recently reported in literature, that was also designed on the basis of the mechanical structure, actuators, and power stage subsystems. Although both controllers are robust when parametric disturbances are taken into account, the dynamic three-level tracking controller presented in this paper is better than the hierarchical tracking controller reported in literature.
Fabrication of ZnO/Carbon Quantum Dots Composite Sensor for Detecting NO Gas
Authors: Yu Ziyang , Zhang Liang , Wang Xiangyue , He Dong , Suo Hui , Zhao Chun
Published: September 2020

ZnO and carbon quantum dots (CQDs) were synthesized by a hydrothermal method, and CQDs were doped into ZnO by a grinding method to fabricate a ZnO/CQDs composite. The X-ray diffraction and the scanning electron microscope revealed that the as-prepared ZnO has a structure of wurtzite hexagonal ZnO and a morphology of a flower-like microsphere which can provide more surface areas to adsorbed gases. The ZnO/CQDs composite has a higher gas sensitivity response to NO gas than ZnO microspheres. A gas sensitivity test of the ZnO/CQDs composite showed that the sensor had a high NO response (238 for 100 ppm NO) and NO selectivity. The detection limit of the ZnO/CQDs composite to NO was 100 ppb and the response and recovery times were 34 and 36 s, respectively. The active functional group provided by CQDs has a significant effect on NO gas sensitivity, and the gas sensitivity mechanism of the ZnO/CQDs composite is discussed.