bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan Contribution to Therapeutic and Vaccinal Approaches for the Control of Leishmaniasis
Authors: Loiseau Philippe M. , Pomel Sébastien , Croft Simon L.
Published: September 2020

The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of Leishmania-infected macrophages. In addition, the immunomodulatory effect of chitosan is an added value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.
Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
Authors: Ciccolini Cecilia , De Crescentini Lucia , Mantellini Fabio , Mari Giacomo , Santeusanio Stefania , Favi Gianfranco
Published: September 2020

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles.
Thymol and Thyme Essential Oil—New Insights into Selected Therapeutic Applications
Authors: Kowalczyk Adam , Przychodna Martyna , Sopata Sylwia , Bodalska Agnieszka , Fecka Izabela
Published: September 2020

Thymol (2-isopropyl-5-methylphenol) belongs to the phenolic monoterpenes and mostly occurs in thyme species. It is one of the main compounds of thyme essential oil. Both thymol and thyme essential oil have long been used in traditional medicine as expectorant, anti-inflammatory, antiviral, antibacterial, and antiseptic agents, mainly in the treatment of the upper respiratory system. The current search for new directions of biological or therapeutic activities of natural plant substances with known structures includes thyme essential oil and thymol. Novel studies have demonstrated their antibiofilm, antifungal, antileishmanial, antiviral, and anticancer properties. Also, their new therapeutic formulations, such as nanocapsules containing these constituents, can be beneficial in medicinal practice and create opportunities for their extensive use. Extensive application of thymol and thyme essential oil in the healthcare sector is very promising but requires further research and analysis.
Dielectric Relaxation Characteristics of Epoxy Resin Modified with Hydroxyl-Terminated Nitrile Rubber
Authors: Chen Chi , Sun Qing , Wang Chuang , Bu Yue , Zhang Jiawei , Peng Zongren
Published: September 2020

Utilizing liquid rubber to toughen epoxy resin is one of the most mature and promising methods. However, the dielectric relaxation characteristics of the epoxy/liquid rubber composites have not been studied systematically, while the relaxation behaviours are a critical factor for both micro and macro properties. In this paper, hydroxyl-terminated liquid nitrile rubber (HTBN) is employed to reinforce a kind of room-temperature-cured epoxy resin. The dielectric spectrum is measured and analysed. Results show that two relaxation processes are introduced in the binary composites. The α relaxation of HTBN shows a similar temperature dependence with the β relaxation of epoxy resin. The interfacial polarization leads to an increase of complex permittivity, which reaches its maximum at 70 °C. In addition, affected by interfacial polarization, the thermionic polarization is inhibited, and the samples with filler ratios of 15% and 25% show lower DC-conductivity below 150 °C. In addition, the α relaxation and thermionic polarization of epoxy resin obey the Vogel‒Fulcher‒Tammann law, while the interfacial polarization and DC-conductivity satisfy with the Arrhenius law. Furthermore, the fitting results of the Vogel temperature of α relaxation, glass transition temperature, apparent activation energy of interfacial polarization and DC-conductivity all decline with HTBN content. These results can provide a reference and theoretical guidance for the assessment of dielectric properties and the improvement of the formulation of liquid-rubber-toughened epoxy resin.
Glucose-Uptake Activity and Cytotoxicity of Diterpenes and Triterpenes Isolated from Lamiaceae Plant Species
Authors: Etsassala Ninon G. E. R. , Ndjoubi Kadidiatou O. , Mbira Thilly J. , Pearce Brendon , Pearce Keenau , Iwuoha Emmanuel I. , Hussein Ahmed A. , Benjeddou Mongi
Published: September 2020

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rates of morbidity and mortality around the world in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristics of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species: namely, Salvia africana-lutea, Leonotis ocymifolia, and Plectranthus madagascariensis, for their glucose-uptake ability. Methanolic extracts were produced from the aerial parts of each plant. Compounds were identified using different spectroscopic techniques. The glucose-uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded sixteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086) showed a marked increase in glucose uptake, respectively. Additionally, 1, 4, and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68%, and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake, while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.
The Microbiota-Derived Metabolite of Quercetin, 3,4-Dihydroxyphenylacetic Acid Prevents Malignant Transformation and Mitochondrial Dysfunction Induced by Hemin in Colon Cancer and Normal Colon Epithelia Cell Lines
Authors: Catalán Mabel , Ferreira Jorge , Carrasco-Pozo Catalina
Published: September 2020

Meat diet plays a pivotal role in colorectal cancer (CRC). Hemin, a metabolite of myoglobin, produced after meat intake, has been involved in CRC initiation. The compound, 3,4-dihydroxyphenylacetic acid (3,4HPAA) is a scarcely studied microbiota-derived metabolite of the flavonoid quercetin (QUE), which exert antioxidant properties. The aim of this study was to determine the protective effect of 3,4HPAA against malignant transformation (increased cell proliferation, decreased apoptosis, DNA oxidative damage and augmented reactive oxidative species (ROS) levels) and mitochondrial dysfunction induced by hemin in normal colon epithelial cells and colon cancer cells. The effect of 3,4HPAA was assessed in comparison to its precursor, QUE and to a known CRC protective agent, sulforaphane (SFN). The results showed that both, tumor and normal cells, exposed to hemin, presented increased cell proliferation, decreased caspase 3 activity and cytochrome c release, as well as augmented production of intracellular and mitochondrial ROS. In addition, hemin decreased the mitochondrial membrane potential (MMP) and the activity of complexes I and II of the electron transport chain. These effects of hemin were prevented by the action of 3,4HPAA. The metabolite showed to be more active than QUE and slightly less active than SFN. In conclusion, 3,4HPAA administration could represent a promising strategy for preventing malignant transformation and mitochondrial dysfunction in colon epithelia induced by hemin.
The Effects of Temperature and Ethanol on Proanthocyanidin Adsorption to Grape Cell Wall Material in the Presence of Anthocyanins
Authors: Beaver Jordan W. , Miller Konrad V. , Medina-Plaza Cristina , Dokoozlian Nick , Ponangi Ravi , Blair Thomas , Block David , Oberholster Anita
Published: September 2020

The quantitative and qualitative impacts of anthocyanins on proanthocyanidin adsorption to grape-derived cell wall material were investigated in fifteen unique systems of varying temperatures, ethanol concentrations, and proanthocyanidin concentrations. Proanthocyanidin solutions were exposed to cell wall material and monitored for changes in concentration over 24 h. Increases in both temperature and ethanol resulted in a larger retention of proanthocyanidins in solution and typically faster adsorption kinetics. Analysis of the solution after exposure to cell wall revealed a significant reduction in the molecular weight of proanthocyanidins present in solution, suggesting that anthocyanins do not alter a previously described mechanism of preferentially binding large molecular weight molecules. Additionally, a reduction in polymeric pigment abundance was noted in most conditions, suggesting rapid formation of polymeric pigment in the model solution and preferential adsorption of the polymeric pigment to cell wall material. Compared to a previous study of proanthocyanidin adsorption in the absence of anthocyanins, a significantly larger percentage of proanthocyanidin material was lost via adsorption—up to 70% of available material. In a winemaking context, this may suggest a preferential loss of polymeric pigment via adsorption to cap cell wall material compared to non-pigmented proanthocyanidins and free anthocyanins.
Molecules Isolated from Mexican Hypoglycemic Plants: A Review
Authors: Escandón-Rivera Sonia Marlen , Mata Rachel , Andrade-Cetto Adolfo
Published: September 2020

Like in many developing countries, in Mexico, the use of medicinal plants is a common practice. Based on our own field experience, there are at least 800 plants used for treating diabetes nowadays. Thus, their investigation is essential. In this context, this work aims to provide a comprehensive and critical review of the molecules isolated from Mexican hypoglycemic plants, including their source and target tested. In the last few years, some researchers have focused on the study of Mexican hypoglycemic plants. Most works describe the hypoglycemic effect or the mechanism of action of the whole extract, as well as the phytochemical profile of the tested extract. Herein, we analyzed 85 studies encompassing 40 hypoglycemic plants and 86 active compounds belonging to different classes of natural products: 28 flavonoids, 25 aromatic compounds, other than flavonoids, four steroids, 23 terpenoids, 4 oligosaccharides, and 1 polyalcohol. These compounds have shown to inhibit α-glucosidases, increase insulin secretion levels, increase insulin sensitivity, and block hepatic glucose output. Almost half of these molecules are not common metabolites, with a narrow taxonomic distribution, which makes them more interesting as lead molecules. Altogether, this analysis provides a necessary inventory useful for future testing of these active molecules against different hypoglycemic targets, to get a better insight into the already described mechanisms, and overall, to contribute to the knowledge of Mexican medicinal plants.
Spherical Bi2WO6/Bi2S3/MoS2 n-p Heterojunction with Excellent Visible-Light Photocatalytic Reduction Cr(VI) Activity
Authors: Ren Jing , Hu Tingting , Gong Qinghua , Wang Qian , Sun Bin , Gao Tingting , Cao Pei , Zhou Guowei
Published: September 2020

Exploiting excellent photocatalytic activity and stable heterostructure composites are of critical importance for environmental sustainability. The spherical Bi2WO6/Bi2S3/MoS2 n-p heterojunction is first prepared via an in situ hydrothermal method using Bi2WO6, Na2MoO4·2H2O, and CH4N2S, in which the intermediate phase Bi2S3 is formed due to chemical coupling interaction of Bi2WO6 and CH4N2S. Scanning electron microscopy indicates that the compactness of the sample can be easily adjusted by changing the contents of S and Mo sources in the solution. The results of ultraviolet–visible (UV–vis) diffuse reflectance spectra, photoluminescence, transient photocurrent response, and electrochemical impedance spectra indicate that the formation of heterojunctions contributes to enhancing visible-light utilization and promoting photogenerated carrier separation and transfer. The composite material is used as a catalyst for the visible light photocatalytic reduction of Cr(VI). Remarkably, the optimal Bi2WO6/Bi2S3/MoS2 n-p heterojunction achieves the greatest Cr(VI) reduction rate of 100% within 75 min (λ > 420 nm, pH = 2); this rate is considerably better than the Cr(VI) reduction rate of pure Bi2WO6. The recycling experiment also reveals that the photocatalytic performance of the n-p heterojunction toward Cr(VI) is still maintained at 80% after three cycles, indicating that the n-p heterojunction has excellent structural stability. The capture experiment proves that the main active species in the system are electrons. The reasonable mechanism of Bi2WO6/Bi2S3/MoS2 photocatalytic reduction Cr(VI) is proposed. Our work provides new research ideas for the design of ternary heterojunction composites and new strategies for the development of photocatalysts for wastewater treatment.
Reinforcing Mechanisms of Graphene and Nano-TiC in Al2O3-Based Ceramic-Tool Materials
Authors: Sun Zhefei , Zhao Jun , Wang Xuchao , Cui Enzhao , Yu Hao
Published: September 2020

Graphene and nano-TiC, which have good reinforcing effects on Al2O3-based ceramic-tool materials, are generally used as additive phases for ceramics. In this study, nine kinds of samples were sintered, to investigate the effects of graphene and nano-TiC on the reinforcing mechanisms of Al2O3-based ceramics. The experimental results indicated that adding 0.5 vol% graphene and 10 vol% nano-TiC can obtain the optimum flexural strength, fracture toughness, and Vickers hardness, which were 705 ± 44 MPa, 7.4 ± 0.4 MPa m1/2, and 20.5 ± 0.8 GPa, respectively. Furthermore, the reinforcing mechanisms of crack bridging, pull-out of graphene, and pull-out of nano-TiC are identified, which are contributed to improving the mechanical properties of ceramics. Meanwhile, other reinforcing mechanisms induced by graphene (graphene break, crack guiding, and 3D propagation) and nano-TiC (crack branching, crack deflection, and peeling) are discussed. These reinforcing mechanisms are coupled together, while decoupling is hard to work out. Thus, further quantitative studies of reinforcing effects of graphene and nano-TiC on Al2O3-based ceramic-tool materials are necessary to be carried out.
Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape
Authors: Rueda-Gensini Laura , Cifuentes Javier , Castellanos Maria Claudia , Puentes Paola Ruiz , Serna Julian A. , Muñoz-Camargo Carolina , Cruz Juan C.
Published: September 2020

Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.
The Impact of a Polyphenol-Rich Extract from the Berries of Aronia melanocarpa L. on Collagen Metabolism in the Liver: A Study in an In Vivo Model of Human Environmental Exposure to Cadmium
Authors: Kozłowska Magdalena , Brzóska Małgorzata M. , Rogalska Joanna , Galicka Anna
Published: September 2020

This study examined whether a polyphenol-rich extract from the berries of Aronia melanocarpa L. (AE; chokeberries) may protect from the impact of cadmium (Cd) on the metabolism of collagen in the liver. The study was conducted in an experimental model (rats that were fed a diet containing 1 or 5 mg Cd/kg for 3–24 months) of human exposure to this xenobiotic during a lifetime. The concentration of total collagen and the expression of collagen types I and III at the mRNA and protein levels, as well as the concentrations of matrix metalloproteinases (MMP-1 and MMP-2) and their tissue inhibitors (TIMP-1 and TIMP-2), were assayed. The administration of Cd and/or AE had only a slight and temporary impact on the concentration of total collagen in the liver. The supplementation with AE significantly prevented Cd-mediated changes in the expression of collagen types I and III at the mRNA and protein levels and their ratio (collagen III/collagen I), as well as a rise in the concentrations of MMPs and TIMPs in this organ. The results allow the conclusion that the intake of chokeberry products in the case of Cd intoxication may be effective in prevention from this xenobiotic-induced disturbance in collagen homeostasis in the liver.
Eating Fast Has a Significant Impact on Glycemic Excursion in Healthy Women: Randomized Controlled Cross-Over Trial
Authors: Saito Yuuki , Kajiyama Shizuo , Nitta Ayasa , Miyawaki Takashi , Matsumoto Shinya , Ozasa Neiko , Kajiyama Shintaro , Hashimoto Yoshitaka , Fukui Michiaki , Imai Saeko
Published: September 2020

Epidemiological studies have shown that self-reported fast eating increases the risk of diabetes and obesity. Our aim was to evaluate the acute effect of fast eating on glycemic parameters through conducting a randomized controlled cross-over study with young healthy women. Nineteen healthy women wore a flash glucose monitoring system for 6 days. Each participant consumed identical test meals with a different eating speed of fast eating (10 min) or slow eating (20 min) on the 4th or the 5th day. The daily glycemic parameters were compared between the 2 days. The mean amplitude of glycemic excursion (MAGE; fast eating 3.67 ± 0.31 vs. slow eating 2.67 ± 0.20 mmol/L, p < 0.01), incremental glucose peak (IGP; breakfast 2.30 ± 0.19 vs. 1.71 ± 0.12 mmol/L, p < 0.01, lunch 4.06 ± 0.33 vs. 3.13 ± 0.28 mmol/L, p < 0.01, dinner 3.87 ± 0.38 vs. 2.27 ± 0.27 mmol/L, p < 0.001), and incremental area under the curve for glucose of dinner 2 h (IAUC; 256 ± 30 vs. 128 ± 18 mmol/L × min, p < 0.001) for fast eating were all significantly higher than those for slow eating. The results suggest that fast eating is associated with higher glycemic excursion in healthy women.
Intensive Running Enhances NF-κB Activity in the Mice Liver and the Intervention Effects of Quercetin
Authors: Gao Chao , Liu Yang , Jiang Chunjie , Liu Liang , Li Juan , Li Dan , Guo Xiaoping , Wang Zhu , Yang Yuexin , Liu Liegang , Yao Ping , Tang Yuhan
Published: September 2020

Background: Emerging evidence has supported that intensive exercise induces weakened performance and immune and metabolic disorders. We systematically evaluated the effects of quercetin against hepatic inflammatory damage caused by repeated intensive exercise and explored the potential mechanism. Methods: Male BALB/c mice were administered quercetin (100 mg/kg BW) for four weeks, and performed a treadmill running protocol of 28 m/min, 5° slope, 90 min/day concurrently for the last seven days. Results: Quercetin administration reduced the leakage of aspartic acid and alanine aminotransferase and improved ultrastructural abnormalities such as swelling, and degeneration caused by high-intensity running in mice. Quercetin significantly decreased the hepatic and plasmatic levels of inflammatory cytokines IL-1β, IL-6, TNF-α, inducible nitric oxide synthase, cyclooxygenase-2 and intercellular adhesion molecule-1—provoked by over-exercise. Furthermore, diminished activation and nuclear translocation of NF-κB were found after quercetin treatment through inhibiting IKKα and Iκbα phosphorylation of intensive running mice. Conclusion: Quercetin offers protection for mouse livers against intensive sports-induced inflammatory injury, and the suppression of the NF-κB signal transduction pathway may play a role in its anti-inflammatory effects. Our findings broaden our understanding of natural phytochemicals as a promising strategy to prevent excessive exercise damage.
Urinary Sodium Excretion and Blood Pressure Relationship across Methods of Evaluating the Completeness of 24-h Urine Collections
Authors: Naser Abu Mohd , He Feng J. , Rahman Mahbubur , Narayan K. M. Venkat , Campbell Norm R. C.
Published: September 2020

We compared the sodium intake and systolic blood pressure (SBP) relationship from complete 24-h urine samples determined by several methods: self-reported no-missed urine, creatinine index ≥0.7, measured 24-h urine creatinine (mCER) within 25% and 15% of Kawasaki predicted urine creatinine, and sex-specific mCER ranges (mCER 15–25 mg/kg/24-h for men; 10–20 mg/kg/24-h for women). We pooled 10,031 BP and 24-h urine sodium data from 2143 participants. We implemented multilevel linear models to illustrate the shape of the sodium–BP relationship using the restricted cubic spline (RCS) plots, and to assess the difference in mean SBP for a 100 mmol increase in 24-h urine sodium. The RCS plot illustrated an initial steep positive sodium–SBP relationship for all methods, followed by a less steep positive relationship for self-reported no-missed urine, creatinine index ≥0.7, and sex-specific mCER ranges; and a plateaued relationship for the two Kawasaki methods. Each 100 mmol/24-h increase in urinary sodium was associated with 0.64 (95% CI: 0.34, 0.94) mmHg higher SBP for self-reported no-missed urine, 0.68 (95% CI: 0.27, 1.08) mmHg higher SBP for creatinine index ≥0.7, 0.87 (95% CI: 0.07, 1.67) mmHg higher SBP for mCER within 25% Kawasaki predicted urine creatinine, 0.98 (95% CI: −0.07, 2.02) mmHg change in SBP for mCER within 15% Kawasaki predicted urine creatinine, and 1.96 (95% CI: 0.93, 2.99) mmHg higher SBP for sex-specific mCER ranges. Studies examining 24-h urine sodium in relation to health outcomes will have different results based on how urine collections are deemed as complete.
Impact of Ascorbic Acid on the In Vitro Iron Bioavailability of a Casein-Based Iron Fortificant
Authors: Sabatier Magalie , Rytz Andreas , Husny Joeska , Dubascoux Stéphane , Nicolas Marine , Dave Anant , Singh Harjinder , Bodis Mary , Glahn Raymond P.
Published: September 2020

A new iron–casein complex (ICC) has been developed for iron (Fe) fortification of dairy matrices. The objective was to assess the impact of ascorbic acid (AA) on its in vitro bioavailability in comparison with ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). A simulated digestion coupled with the Caco-2 cell culture model was used in parallel with solubility and dissociation tests. Under diluted acidic conditions, the ICC was as soluble as FeSO4, but only part of the iron was found to dissociate from the caseins, indicating that the ICC was an iron chelate. The Caco-2 cell results in milk showed that the addition of AA (2:1 molar ratio) enhanced iron uptake from the ICCs and FeSO4 to a similar level (p = 0.582; p = 0.852) and to a significantly higher level than that from FePP (p < 0.01). This translated into a relative in vitro bioavailability to FeSO4 of 36% for FePP and 114 and 104% for the two ICCs. Similar results were obtained from water. Increasing the AA to iron molar ratio (4:1 molar ratio) had no additional effect on the ICCs and FePP. However, ICC absorption remained similar to that from FeSO4 (p = 0.666; p = 0.113), and was still significantly higher than that from FePP (p < 0.003). Therefore, even though iron from ICC does not fully dissociate under gastric digestion, iron uptake suggested that ICCs are absorbed to a similar amount as FeSO4 in the presence of AA and thus provide an excellent source of iron.
Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet
Authors: Son Myeongjoo , Oh Seyeon , Jang Ji Tae , Park Chul-Hyun , Son Kuk Hui , Byun Kyunghee
Published: September 2020

Advanced glycation end products/receptor for AGEs (AGEs/RAGEs) or Toll like receptor 4 (TLR4) induce vascular smooth muscle cell (VSMC) phenotype changes in osteoblast-like cells and vascular calcification. We analyzed the effect of Ecklonia cava extract (ECE) or pyrogallol-phloroglucinol-6,6-bieckol (PPB) on VSMC phenotype changes and vascular calcification prompted by a high-fat diet (HFD). HFD unregulated RAGE, TLR4, transforming growth factor beta (TGFβ), bone morphogenetic protein 2 (BMP2), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signals in the aorta of mice. ECE and PPB restored the increase of those signal pathways. AGE- or palmitate-treated VSMC indicated similar changes with the animal. HFD increased osteoblast-like VSMC, which was evaluated by measuring core-binding factor alpha-1 (CBFα-1) and osteocalcin expression and alkaline phosphatase (ALP) activity in the aorta. ECE and PPB reduced vascular calcification, which was analyzed by the calcium deposition ratio, and Alizarin red S stain was increased by HFD. PPB and ECE reduced systolic, diastolic, and mean blood pressure, which increased by HFD. PPB and ECE reduced the phenotype changes of VSMC to osteoblast-like cells and vascular calcification and therefore lowered the blood pressure.
Effect of Konjac Glucomannan (KGM) on the Reconstitution of the Dermal Environment against UVB-Induced Condition
Authors: Choi Kyung Ho , Kim Sung Tae , Bin Bum Ho , Park Phil June
Published: September 2020

Skin layers serve as a barrier against unexpected critical changes in the body due to environmental factors. Excessive ultraviolet (UV) B exposure increases the levels of age-related factors, leading to senescent cells and damaged skin tissues. Widely used as a dietary supplement, konjac (Amorphophallus konjac) glucomannan (KGM) has shown skin regeneration potential in patch or sheet form with anti-inflammatory or immunosuppressive effects. However, the ability of KGM to reconstitute senescent/damaged skin following UV radiation has not been explored. Here, we demonstrate that KGM alleviates skin damage by increasing the proportion of young cell populations in UVB-exposed senescent human epidermal primary melanocytes. Young cell numbers increased depending on KGM dosage, but the senescent cells were not removed. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis showed that mRNA and protein levels of age- and pigmentation-related factors decreased in a manner dependent on the rate at which new cells were generated. Moreover, an analysis of mRNA and protein levels indicated that KGM facilitated youth by increasing cell proliferation in UVB-damaged human fibroblasts. Thus, KGM is a highly effective natural agent for maintaining skin homeostasis by promoting the reconstitution of the dermal environment against UVB-induced acute senescence or skin damage.
Nutrition, Bioenergetics, and Metabolic Syndrome
Authors: García-García Francesc Josep , Monistrol-Mula Anna , Cardellach Francesc , Garrabou Glòria
Published: September 2020

According to the World Health Organization (WHO), the global nutrition report shows that whilst part of the world’s population starves, the other part suffers from obesity and associated complications. A balanced diet counterparts these extreme conditions with the proper proportion, composition, quantity, and presence of macronutrients, micronutrients, and bioactive compounds. However, little is known on the way these components exert any influence on our health. These nutrients aiming to feed our bodies, our tissues, and our cells, first need to reach mitochondria, where they are decomposed into CO2 and H2O to obtain energy. Mitochondria are the powerhouse of the cell and mainly responsible for nutrients metabolism, but they are also the main source of oxidative stress and cell death by apoptosis. Unappropriated nutrients may support mitochondrial to become the Trojan horse in the cell. This review aims to provide an approach to the role that some nutrients exert on mitochondria as a major contributor to high prevalent Western conditions including metabolic syndrome (MetS), a constellation of pathologic conditions which promotes type II diabetes and cardiovascular risk. Clinical and experimental data extracted from in vitro animal and cell models further demonstrated in patients, support the idea that a balanced diet, in a healthy lifestyle context, promotes proper bioenergetic and mitochondrial function, becoming the best medicine to prevent the onset and progression of MetS. Any advance in the prevention and management of these prevalent complications help to face these challenging global health problems, by ameliorating the quality of life of patients and reducing the associated sociosanitary burden.
New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab
Authors: Musso Nicolò , Costantino Angelita , La Spina Sebastiano , Finocchiaro Alessandra , Andronico Francesca , Stracquadanio Stefano , Liotta Luigi , Visalli Rosanna , Emmanuele Giovanni
Published: September 2020

The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite close pet–human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear clinical signs of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study responding to the request of the scientific community to focus attention on the possible role of pets as a viral reservoir. An important question remains unanswered: did the cat actually die due to SARS-CoV-2 infection?
Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Smart Drug Delivery Systems in the Treatment of Glioblastoma Multiforme
Authors: Jnaidi Raneem , Almeida António José , Gonçalves Lídia M.
Published: September 2020

Glioblastoma multiforme (GBM) is the most common and malignant type of brain tumor. In fact, tumor recurrence usually appears a few months after surgical resection and chemotherapy, mainly due to many factors that make GBM treatment a real challenge, such as tumor location, heterogeneity, presence of the blood-brain barrier (BBB), and others. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) represent the most promising carriers for therapeutics delivery into the central nervous system (CNS) owing to their inherent ability to cross the BBB. In this review, we present the main challenges in GBM treatment, a description of SLNs and NLCs and their valuable role as drug carriers in GBM treatment, and finally, a detailed description of all modification strategies that aim to change composition of SLNs and NLCs to enhance treatment outcomes. This includes modification of SLNs and NLCs to improve crossing the BBB, reduced GBM cell resistance, target GBM cells selectively minimizing side effects, and modification strategies to enhance SLNs and NLCs nose-to-brain delivery. Finally, future perspectives on their use are also be discussed, to provide insight about all strategies with SLNs and NLCs formulation that could result in drug delivery systems for GBM treatment with highly effective theraputic and minimum undesirable effects.
Serine Protease-Mediated Cutaneous Inflammation: Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers
Authors: Frombach Janna , Rancan Fiorenza , Kübrich Katharina , Schumacher Fabian , Unbehauen Michael , Blume-Peytavi Ulrike , Haag Rainer , Kleuser Burkhard , Sabat Robert , Wolk Kerstin , Vogt Annika
Published: September 2020

Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development.
Formulation of Sodium Valproate Nanospanlastics as a Promising Approach for Drug Repurposing in the Treatment of Androgenic Alopecia
Authors: Badria Farid. A. , Fayed Hassan A. , Ibraheem Amira K. , State Ahmed F. , Mazyed Eman A.
Published: September 2020

Sodium valproate (SV) is an antiepileptic drug that is widely used in the treatment of different seizure disorders. The topical SV has a hair regenerative potential through activating the Wnt/β-catenin pathway and anagen phase induction. The aim of the current investigation was to fabricate nanospanlastics of SV for improving its dermal delivery by providing prolonged drug effect and increasing its permeability for treatment of androgenic alopecia (AGA). SV-loaded nanospanlastics were formulated according to 23 factorial design by ethanol injection method using a non-ionic surfactant (Span 60) and edge activators (EAs), such as Tween 80 and Cremophor RH 40, to explore the influence of different independent variables on entrapment efficiency (EE%) and percentage drug released after 12 h (Q12h) in order to choose the optimized formula using Design-Expert software. The optimized formula (F8) appeared as spherical deformable vesicles with EE% of 90.32 ± 2.18% and Q12h of 90.27 ± 1.98%. F8 exhibited significant improvement of ex vivo permeation than free SV. The clinical study exhibited no comparable difference between F8 and marketed minoxidil lotion. However, F8 demonstrates less adverse effects than minoxidil lotion. Nanospanlastics could be a safe and effective method for improving the topical delivery of SV in the management of AGA.
Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E
Authors: Iudin Dmitrii , Zashikhina Natalia , Demyanova Elena , Korzhikov-Vlakh Viktor , Shcherbakova Elena , Boroznjak Roman , Tarasenko Irina , Zakharova Natalya , Lavrentieva Antonina , Skorik Yury , Korzhikova-Vlakh Evgenia
Published: September 2020

Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.
Microsphere-Based Optical Frequency Comb Generator for 200 GHz Spaced WDM Data Transmission System
Authors: Anashkina Elena A. , Marisova Maria P. , Andrianov Alexey V. , Akhmedzhanov Rinat A. , Murnieks Rihards , Tokman Mikhail D. , Skladova Laura , Oladyshkin Ivan V. , Salgals Toms , Lyashuk Ilya , Sorokin Arseniy , Spolitis Sandis , Leuchs Gerd , Bobrovs Vjaceslavs
Published: September 2020

Optical frequency comb (OFC) generators based on whispering gallery mode (WGM) microresonators have a massive potential to ensure spectral and energy efficiency in wavelength-division multiplexing (WDM) telecommunication systems. The use of silica microspheres for telecommunication applications has hardly been studied but could be promising. We propose, investigate, and optimize numerically a simple design of a silica microsphere-based OFC generator in the C-band with a free spectral range of 200 GHz and simulate its implementation to provide 4-channel 200 GHz spaced WDM data transmission system. We calculate microsphere characteristics such as WGM eigenfrequencies, dispersion, nonlinear Kerr coefficient with allowance for thermo-optical effects, and simulate OFC generation in the regime of a stable dissipative Kerr soliton. We show that by employing generated OFC lines as optical carriers for WDM data transmission, it is possible to ensure error-free data transmission with a bit error rate (BER) of 4.5 × 10−30, providing a total of 40 Gbit/s of transmission speed on four channels.
Low-Dimensional Nanostructures for Electrochemical Energy Applications
Authors: Chen Hsin-Yu , Xiao Yi-Hong , Chen Lin-Jiun , Tseng Chi-Ang , Lee Chuan-Pei
Published: September 2020

Materials with different nanostructures can have diverse physical properties, and they exhibit unusual properties as compared to their bulk counterparts. Therefore, the structural control of desired nanomaterials is intensely attractive to many scientific applications. In this brief review, we mainly focus on reviewing our recent reports based on the materials of graphene and the transition metal chalcogenide, which have various low-dimensional nanostructures, in relation to the use of electrocatalysts in electrochemical energy applications; moreover, related literatures were also partially selected for discussion. In addition, future aspects of the nanostructure design related to the further enhancement of the performance of pertinent electrochemical energy devices will also be mentioned.
Effects of Inorganic Salt Solutions on Vigour, Viability, Oxidative Metabolism and Germination Enzymes in Aged Cabbage and Lettuce Seeds
Authors: Adetunji Ademola Emmanuel , Sershen  , Varghese Boby , Pammenter Norman W.
Published: September 2020

This study assessed the potential of pre-hydration treatment with aqueous solutions (electrolysed [cathodic water; CW] and non-electrolysed) prepared from four different inorganic ion combinations: 1 mM CaCl2, 1 µm CaCl2 and 1 mM MgCl2 (CaMg, hereafter), 1 mM MgCl2 and 1 mM NaCl to invigorate controlled deteriorated (CDd) Brassicaoleracea (cabbage) and Lactucasativa (lettuce) seeds by assessing germination, vigour and biochemical markers (electrolyte leakage, lipid peroxidation products, protein carbonylation, and defence and germination associated enzymes) of oxidative stress. Additionally, the possible effects of pH of electrolysed CaMg and NaCl solutions were assessed. The inorganic salt solutions were applied to fresh seeds and seeds deteriorated to 75% viability (P75), 50% viability (P50) and 25% viability (P25); deionised water served as control. The pre-hydration treatment did not enhance normal seedling production in cabbage. However, Ca-containing and CW hydration treatments (CaCl2 CW, CaMg and CaMg CW [6.5], MgCl2 CW, NaCl CW and NaCl CW [6.5]) promoted normal seedling production of CDd lettuce seeds, while seedling vigour was enhanced by CaMg, CaMg CW (6.5), NaCl CW and NaCl CW (6.5) in CDd cabbage seeds, and CaCl2, CaCl2 CW, CaMg, CaMg CW (6.5), MgCl2 CW, NaCl CW and NaCl CW (6.5) in CDd lettuce seeds. The supplementation of Ca, a component of the ionised solutes, and/or the reducing potential of CW contributed to increased normal seedling production in lettuce seeds irrespective of the pH of treatment solutions or degree of deterioration. Overall, the pre-hydration treatments enhanced endogenous antioxidants leading to reduced levels of electrolyte leakage, lipid peroxidation, protein carbonylation, and enhanced germination enzyme activities in lettuce seeds. The study concluded that pre-hydration with selected inorganic salt solutions can invigorate debilitated lettuce seeds.
Chemical Composition of Cuticular Waxes and Pigments and Morphology of Leaves of Quercus suber Trees of Different Provenance
Authors: Simões Rita , Rodrigues Ana , Ferreira-Dias Suzana , Miranda Isabel , Pereira Helena
Published: September 2020

The chemical composition of cuticular waxes and pigments and the morphological features of cork oak (Quercus suber) leaves were determined for six samples with seeds of different geographical origins covering the natural distribution of the species. The leaves of all samples exhibited a hard texture and oval shape with a dark green colour on the hairless adaxial surface, while the abaxial surface was lighter, with numerous stomata and densely covered with trichomes in the form of stellate multicellular hairs. The results suggest an adaptive role of leaf features among samples of different provenance and the potential role of such variability in dealing with varying temperatures and rainfall regimes through local adaptation and phenotypic plasticity, as was seen in the trial site, since no significant differences in leaf traits among the various specimens were found, for example, specific leaf area 55.6–67.8 cm2/g, leaf size 4.6–6.8 cm2 and photosynthetic pigment (total chlorophyll, 31.8–40.4 µg/cm2). The leaves showed a substantial cuticular wax layer (154.3–235.1 µg/cm2) composed predominantly of triterpenes and aliphatic compounds (61–72% and 17–23% of the identified compounds, respectively) that contributed to forming a nearly impermeable membrane that helps the plant cope with drought conditions. These characteristics are related to the species and did not differ among trees of different seed origin. The major identified compound was lupeol, indicating that cork oak leaves may be considered as a potential source of this bioactive compound.
The Active Compounds and Therapeutic Mechanisms of Pentaherbs Formula for Oral and Topical Treatment of Atopic Dermatitis Based on Network Pharmacology
Authors: Chu Man , Tsang Miranda Sin-Man , He Ru , Lam Christopher Wai-Kei , Quan Zhi Bo , Wong Chun Kwok
Published: September 2020

To examine the molecular targets and therapeutic mechanism of a clinically proven Chinese medicinal pentaherbs formula (PHF) in atopic dermatitis (AD), we analyzed the active compounds and core targets, performed network and molecular docking analysis, and investigated interacting pathways. Information on compounds in PHF was obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using the Drugbank database. AD-related genes were gathered using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Network analysis was performed by Cytoscape software and protein-protein interaction was analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources were applied for the enrichment analysis of the potential biological process and pathways associated with the intersection targets between PHF and AD. Autodock software was used to perform protein compound docking analysis. We identified 43 active compounds in PHF associated with 117 targets, and 57 active compounds associated with 107 targets that form the main pathways linked to oral and topical treatment of AD, respectively. Among them, quercetin, luteolin, and kaempferol are key chemicals targeting the core genes involved in the oral use of PHF against AD, while apigenin, ursolic acid, and rosmarinic acid could be used in topical treatment of PHF against AD. The compound–target–disease network constructed in the current study reveals close interactions between multiple components and multiple targets. Enrichment analysis further supports the biological processes and signaling pathways identified, indicating the involvement of IL-17 and tumor necrosis factor signaling pathways in the action of PHF on AD. Our data demonstrated the main compounds and potential pharmacological mechanisms of oral and topical application of PHF in AD.