bluuebunny/crossref_metadata_2025 huggingface dataset:
Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System
Authors: Akimov Mikhail G. , Kudryavtsev Denis S. , Kryukova Elena V. , Fomina-Ageeva Elena V. , Zakharov Stanislav S. , Gretskaya Natalia M. , Zinchenko Galina N. , Serkov Igor V. , Makhaeva Galina F. , Boltneva Natalia P. , Kovaleva Nadezhda V. , Serebryakova Olga G. , Lushchekina Sofya V. , Palikov Victor A. , Palikova Yulia , Dyachenko Igor A. , Kasheverov Igor E. , Tsetlin Victor I. , Bezuglov Vladimir V.
Published: February 2020

Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system. In the radioligand binding assay, acylcholines showed inhibition in the micromolar range of both α7 neuronal nAChR overexpressed in GH4C1 cells and muscle type nAChR from Torpedo californica, as well as Lymnaea stagnalis acetylcholine binding protein. Functional response was checked in two cell lines endogenously expressing α7 nAChR. In SH-SY5Y cells, these compounds did not induce Ca2+ rise, but inhibited the acetylcholine-evoked Ca2+ rise with IC50 9 to 12 μM. In the A549 lung cancer cells, where α7 nAChR activation stimulates proliferation, Ol-CHOL, Ln-CHOL, and AA-CHOL dose-dependently decreased cell viability by up to 45%. AA-CHOL inhibited human erythrocyte acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by a mixed type mechanism with Ki = 16.7 ± 1.5 μM and αKi = 51.4 ± 4.1 μM for AChE and Ki = 70.5 ± 6.3 μM and αKi = 214 ± 17 μM for BChE, being a weak substrate of the last enzyme only, agrees with molecular docking results. Thus, long-chain unsaturated acylcholines could be viewed as endogenous modulators of the acetylcholine signaling system.
Exploration and Characterization of Novel Glycoside Hydrolases from the Whole Genome of Lactobacillus ginsenosidimutans and Enriched Production of Minor Ginsenoside Rg3(S) by a Recombinant Enzymatic Process
Authors: Siddiqi Muhammad Zubair , Srinivasan Sathiyaraj , Park Hye Yoon , Im Wan-Taek
Published: February 2020

Background: Several studies have reported that ginsenoside Rg3(S) is effective in treating metastatic diseases, obesity, and various cancers, however, its presence in white ginseng cannot be estimated, and only a limited amount is present in red ginseng. Therefore, the use of recombinant glycosidases from a Generally Recognized As Safe (GRAS) host strain is a promising approach to enhance production of Rg3(S), which may improve nutritional activity, human health, and quality of life. Method: Lactobacillus ginsenosidimutans EMML 3041T, which was isolated from Korean fermented pickle (kimchi), presents ginsenoside-converting abilities. The strain was used to enrich the production of Rg3(S) by fermenting protopanaxadiol (PPD)-mix-type major ginsenosides (Rb1, Rb2, Rc, and Rd) in four different types of food-grade media (1, MRS; 2, Basel Food-Grade medium; 3, Basel Food-Grade medium-I, and 4, Basel Food-Grade medium-II). Due to its tendency to produce Rg3(S), the presence of glycoside hydrolase in Lactobacillus ginsenosidimutans was proposed, the whole genome was sequenced, and the probable glycoside hydrolase gene for ginsenoside conversion was cloned. Results: The L. ginsenosidimutans EMML 3041T strain was whole genome sequenced to identify the target genes. After genome sequencing, 12 sets of glycoside hydrolases were identified, of which seven sets (α,β-glucosidase and α,β-galactosidase) were cloned in Escherichia coli BL21 (DE3) using the pGEX4T-1 vector system. Among the sets of clones, only one clone (BglL.gin-952) showed ginsenoside-transforming abilities. The recombinant BglL.gin-952 comprised 952 amino acid residues and belonged to glycoside hydrolase family 3. The enzyme exhibited optimal activity at 55 °C and a pH of 7.5 and showed a promising conversion ability of major ginsenoside Rb1→Rd→Rg3(S). The recombinant enzyme (GST-BglL.gin-952) was used to mass produce Rg3(S) from major ginsenoside Rb1. Scale-up of production using 50 g of Rb1 resulted in 30 g of Rg3(S) with 74.3% chromatography purity. Conclusion: Our preliminary data demonstrated that this enzyme would be beneficial in the preparation of pharmacologically active minor ginsenoside Rg3(S) in the functional food and pharmaceutical industries.
Endoglin: Beyond the Endothelium
Authors: Schoonderwoerd Mark J.A. , Goumans Marie-Jose T.H. , Hawinkels Lukas J.A.C.
Published: February 2020

Keywords: endoglin; CD105 TGF-β; BMP9; ALK-1; TRC105; tumor microenvironment
Physico-Chemical Properties and Oxidative Stability of Fixed Oil from Plum Seeds (Prunus domestica Linn.)
Authors: Savic Ivan , Savic Gajic Ivana , Gajic Dragoljub
Published: February 2020

Storage of a great amount of plum kernel waste becomes a challenge for food industry. In this work, the plum seed was used as a source of fixed oil that can be an ingredient of commercial products. Soxhlet extraction was carried out using the different solvents, such as n-hexane, n-heptane, ethyl acetate, acetone, or chloroform:methanol mixture (2:1 v/v). The highest yield of oil (about 30%) was obtained using n-heptane and n-hexane, while the lowest yield was obtained using ethyl acetate. The analysis of physico-chemical parameters indicated that all samples of plum seed oil have an exceptional quality. Schaal oven test indicated that the fixed oil of plum seed exhibited satisfactory oxidative stability at moderate storage temperatures (up to 65 °C). The composition of phenolic compounds in the oil samples was determined using HPLC method. The most abundant compound of seven identified and quantified phenolic compounds was vanillic acid. The highest content of β-carotene (1.67 mg 100 g−1 fixed oil) spectrophotometrically determined was in the oil extracted with n-hexane. The lowest content of β-carotene (1.26 mg 100 g−1 fixed oil) was determined in the oil extracted with a mixture of chloroform:methanol (2:1 v/v). This oil had the highest antioxidant activity (IC50 value of 4.35 mg mL−1) compared to other oil samples. The antioxidant activity was probably caused by the presence of phenolic compounds. The investigated physico-chemical properties demonstrated that the plum seed oil has a potential for application in the food, cosmetics, and pharmaceutical industry.
Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET
Authors: Oh Ha-Na , Lee Mee-Hyun , Kim Eunae , Kwak Ah-Won , Yoon Goo , Cho Seung-Sik , Liu Kangdong , Chae Jung-Il , Shim Jung-Hyun
Published: February 2020

Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant Glycyrrhiza inflata, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of MET (hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer.
Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma
Authors: Wang Jian , Li Cun-Di , Sun Lin
Published: February 2020

Hepatocellular carcinoma is a common malignant tumor with high mortality. Its malignant proliferation, invasion, and metastasis are closely related to the cellular immune function of the patients. NKG2D is a key activated and type II membrane protein molecule expressed on the surface of almost all NK cells. The human NKG2D gene is 270 kb long, located at 12p12.3–p13.1, and contains 10 exons and 9 introns. The three-dimensional structure of the NKG2D monomeric protein contains two alpha-helices, two beta-lamellae, and four disulfide bonds, and its’ signal of activation is transmitted mainly by the adaptor protein (DAP). NKG2D ligands, including MICA, MICB, and ULBPs, can be widely expressed in hepatoma cells. After a combination of NKG2D and DAP10 in the form of homologous two polymers, the YxxM motif in the cytoplasm is phosphorylated and then signaling pathways are also gradually activated, such as PI3K, PLCγ2, JNK-cJunN, and others. Activated NK cells can enhance the sensitivity to hepatoma cells and specifically dissolve by releasing a variety of cytokines (TNF-α and IFN-γ), perforin, and high expression of FasL, CD16, and TRAIL. NK cells may specifically bind to the over-expressed MICA, MICB, and ULBPs of hepatocellular carcinoma cells through the surface activating receptor NKG2D, which can help to accurately identify hepatoma, play a critical role in anti-hepatoma via the pathway of cytotoxic effects, and obviously delay the poor progress of hepatocellular carcinoma.
Phytochemicals in Garlic Extract Inhibit Therapeutic Enzyme DPP-4 and Induce Skeletal Muscle Cell Proliferation: A Possible Mechanism of Action to Benefit the Treatment of Diabetes Mellitus
Authors: Kalhotra Poonam , Chittepu Veera C.S.R. , Osorio-Revilla Guillermo , Gallardo-Velazquez Tzayhri
Published: February 2020

Diabetes mellitus is a severe health problem in Mexico, and its prevalence is increasing exponentially every year. Recently, DPP-4 (dipeptidyl peptidase-4) inhibitors have become attractive oral anti-hyperglycemic agents to reduce the pathology of diabetes. Gliptin’s family, such as sitagliptin, vildagliptin, and alogliptin, are in clinical use to treat diabetes mellitus but possess side effects. Therefore, there is a specific need to look for new therapeutic scaffolds (biomolecules). Garlic bulb is widely used as a traditional remedy for the treatment of diabetes. The garlic extracts are scientifically proven to control glucose levels in patients with diabetes, despite the unknown mechanism of action. The aim of the study is to investigate the antidiabetic effects of ultrasonication assisted garlic bulb extract. To achieve this, in-vitro assays such as DPP-4 inhibitory and antioxidant activities were investigated. Further, functional group analysis using FTIR and identification of phytochemicals using mass spectrometry analysis was performed. The results showed that 70.9 µg/mL of garlic bulb extract inhibited 50% DPP-4 activity. On top of that, the garlic extract exhibited a 20% scavenging activity, equivalent to 10 µg/mL of ascorbic acid. Molecular docking simulations on identified phytochemicals using mass spectrometry revealed their potential binding at the DPP-4 druggable region, and therefore the possible DPP-4 inhibition mechanism. These results suggest that prepared garlic extract contains phytochemicals that inhibit DPP-4 and have antioxidant activity. Also, the prepared extract induces skeletal muscle cell proliferation that demonstrates the antidiabetic effect and its possible mechanism of action.
p53’s Extended Reach: The Mutant p53 Secretome
Authors: Pavlakis Evangelos , Stiewe Thorsten
Published: February 2020

p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding TP53 gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome. In this review, we discuss how the loss or dominant-negative inhibition of wild-type p53 in concert with a gain of neomorphic properties observed for many mutant p53 proteins, shapes a tumor cell secretome that creates a supportive microenvironment at the primary tumor site and primes niches in distant organs for future metastatic colonization.
Brain Cytoplasmic RNAs in Neurons: From Biosynthesis to Function
Authors: Lee Younghoon , Lee Hee-Seung , Kim Meehyein , Shin Heegwon
Published: February 2020

Flexibility in signal transmission is essential for high-level brain function. This flexibility is achieved through strict spatial and temporal control of gene expression in neurons. Given the key regulatory roles of a variety of noncoding RNAs (ncRNAs) in neurons, studying neuron-specific ncRNAs provides an important basis for understanding molecular principles of brain function. This approach will have wide use in understanding the pathogenesis of brain diseases and in the development of therapeutic agents in the future. Brain cytoplasmic RNAs (BC RNAs) are a leading paradigm for research on neuronal ncRNAs. Since the first confirmation of brain-specific expression of BC RNAs in 1982, their investigation has been an area of active research. In this review, we summarize key studies on the characteristics and functions of BC RNAs in neurons.
Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement
Authors: Batista-Duharte Alexander , Sendra Luis , Herrero Maria , Téllez-Martínez Damiana , Carlos Iracilda , Aliño Salvador
Published: February 2020

Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines.
Generation and Characterization of a CRISPR/Cas9—Induced 3-mst Deficient Zebrafish
Authors: Katsouda Antonia , Peleli Maria , Asimakopoulou Antonia , Papapetropoulos Andreas , Beis Dimitris
Published: February 2020

3-mercaptopyruvate sulfurtransferase (3-MST) is an enzyme capable of synthesizing hydrogen sulfide (H2S) and polysulfides. In spite of its ubiquitous presence in mammalian cells, very few studies have investigated its contribution to homeostasis and disease development, thus the role of 3-MST remains largely unexplored. Here, we present a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR–associated protein-9 (Cas9) induced 3-mst mutant zebrafish line, which will allow the study of 3-MST’s role in several biological processes. The 3-mst zebrafish orthologue was identified using a bioinformatic approach and verified by its ability to produce H2S in the presence of 3-mercaptopyruvate (3-MP). Its expression pattern was analyzed during zebrafish early development, indicating predominantly an expression in the heart and central nervous system. As expected, no detectable levels of 3-Mst protein were observed in homozygous mutant larvae. In line with this, H2S levels were reduced in 3-mst−/− zebrafish. Although the mutants showed no obvious morphological deficiencies, they exhibited increased lethality under oxidative stress conditions. The elevated levels of reactive oxygen species, detected following 3-mst deletion, are likely to drive this phenotype. In line with the increased ROS, we observed accelerated fin regenerative capacity in 3-mst deficient zebrafish. Overall, we provide evidence for the expression of 3-mst in zebrafish, confirm its important role in redox homeostasis and indicate the enzyme’s possible involvement in the regeneration processes.
Current Advances in Allosteric Modulation of Muscarinic Receptors
Authors: Jakubik Jan , El-Fakahany Esam E.
Published: February 2020

Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated G-protein-coupled receptors. They are a potential therapeutic target for the treatment of psychiatric, neurologic, and internal diseases like schizophrenia, Alzheimer’s disease, Huntington disease, type 2 diabetes, or chronic pulmonary obstruction. Here, we reviewed the progress made during the last decade in our understanding of their mechanisms of binding, allosteric modulation, and in vivo actions in order to understand the translational impact of studying this important class of pharmacological agents. We overviewed newly developed allosteric modulators of muscarinic receptors as well as new spin-off ideas like bitopic ligands combining allosteric and orthosteric moieties and photo-switchable ligands based on bitopic agents.
Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy
Authors: Saladrigas-Manjón Sergi , Dučić Tanja , Galindo Liliana , Fernández-Avilés Cristina , Pérez Víctor , de la Torre Rafael , Robledo Patricia
Published: February 2020

Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the neurobiological underpinnings of SCZ, there is an important lack of studies in human neuronal tissue and living cells addressing the effects of cannabis in SCZ patients. In this study, we analysed the most relevant bio-macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non-cannabis users, healthy cannabis users, SCZ patients non-cannabis users, and SCZ patients cannabis users using Synchrotron Radiation-Fourier Transform Infrared (SR-FTIR) spectrometry and microscopy. Our results revealed that SCZ patients non-cannabis users, and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells, including disruption in lipid composition, increased lipid membrane renewal rate and lipid peroxidation, altered proteins containing more β-sheet structures, and showed an increase in DNA and histone methylation. Notably, these alterations were not observed in SCZ patients who use cannabis regularly. These data suggest a differential effect of cannabis in healthy controls and in SCZ patients in terms of the macromolecular constituents of ON cells.
NAD+ Metabolism and Regulation: Lessons From Yeast
Authors: Croft Trevor , Venkatakrishnan Padmaja , Lin Su-Ju
Published: February 2020

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite involved in various cellular processes. The cellular NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human. NAD+ metabolism is an emerging therapeutic target for several human disorders including diabetes, cancer, and neuron degeneration. Factors regulating NAD+ homeostasis have remained incompletely understood due to the dynamic nature and complexity of NAD+ metabolism. Recent studies using the genetically tractable budding yeast Saccharomyces cerevisiae have identified novel NAD+ homeostasis factors. These findings help provide a molecular basis for how may NAD+ and NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function. Here we summarize major NAD+ biosynthesis pathways, selected cellular processes that closely connect with and contribute to NAD+ homeostasis, and regulation of NAD+ metabolism by nutrient-sensing signaling pathways. We also extend the discussions to include possible implications of NAD+ homeostasis factors in human disorders. Understanding the cross-regulation and interconnections of NAD+ precursors and associated cellular pathways will help elucidate the mechanisms of the complex regulation of NAD+ homeostasis. These studies may also contribute to the development of effective NAD+-based therapeutic strategies specific for different types of NAD+ deficiency related disorders.
Characterization of a Novel Mannose-Binding Lectin with Antiviral Activities from Red Alga, Grateloupia chiangii
Authors: Hwang Hyun-Ju , Han Jin-Wook , Jeon Hancheol , Cho Kichul , Kim Ju-hee , Lee Dae-Sung , Han Jong Won
Published: February 2020

Lectins have the ability to bind specific carbohydrates and they have potential applications as medical and pharmacological agents. The unique structure and usefulness of red algal lectin have been reported, but these lectins are limited to a few marine algal groups. In this study, a novel mannose-binding lectin from Grateloupia chiangii (G. chiangii lectin, GCL) was purified using antiviral screens and affinity chromatography. We characterized the molecular weight, agglutination activity, hemagglutination activity, and heat stability of GCL. To determine the carbohydrate specificity, a glycan microarray was performed. GCL showed strong binding affinity for Maltohexaose-β-Sp1 and Maltoheptaose-β-Sp1 with weak affinity for other monosaccharides and preferred binding to high-mannan structures. The N-terminal sequence and peptide sequence of GCL were determined using an Edman degradation method and LC-MS/MS, and the cDNA and peptide sequences were deduced. GCL was shown to consist of 231 amino acids (24.9 kDa) and the N-terminus methionine was eliminated after translation. GCL possessed a tandem repeat structure of six domains, similar to the other red algal lectins. The mannose binding properties and tandem repeat structure of GCL may confer it the potential to act as an antiviral agent for protection against viral infection.
Anti-Infectives Restore ORKAMBI® Rescue of F508del-CFTR Function in Human Bronchial Epithelial Cells Infected with Clinical Strains of P. aeruginosa
Authors: Laselva Onofrio , Stone Tracy A. , Bear Christine E. , Deber Charles M.
Published: February 2020

Chronic infection and inflammation are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. ORKAMBI® (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) protein. It has been previously shown that ORKAMBI®-mediated rescue of CFTR is reduced by a pre-existing Pseudomonas aeruginosa infection. Here, we show that the infection of F508del-CFTR human bronchial epithelial (HBE) cells with lab strain and four different clinical strains of P. aeruginosa, isolated from the lung sputum of CF patients, decreases CFTR function in a strain-specific manner by 48 to 88%. The treatment of infected cells with antibiotic tobramycin or cationic antimicrobial peptide 6K-F17 was found to decrease clinical strain bacterial growth on HBE cells and restore ORKAMBI®-mediated rescue of F508del-CFTR function. Further, 6K-F17 was found to downregulate the expression of pro-inflammatory cytokines, interleukin (IL)-8, IL-6, and tumor necrosis factor-α in infected HBE cells. The results provide strong evidence for a combination therapy approach involving CFTR modulators and anti-infectives (i.e., tobramycin and/or 6K-F17) to improve their overall efficacy in CF patients.
Acorus gramineusand and Euodia ruticarpa Steam Distilled Essential Oils Exert Anti-Inflammatory Effects Through Decreasing Th1/Th2 and Pro-/Anti-Inflammatory Cytokine Secretion Ratios In Vitro
Authors: Yeh Tzu-He , Lin Jin-Yuarn
Published: February 2020

To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary splenocytes and peritoneal macrophages. T helper type 1 lymphocytes (Th1) (IL-2), Th2 (IL-5), pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines secreted by correspondent immune cells treated with SDEO samples were determined using enzyme-linked immunosorbent assay. The total amounts of potential phytochemicals, including total flavonoids, polyphenols and saponins, in these two selected SDEOs were measured and correlated with cytokine levels secreted by immune cells. Our results evidenced that ER SDEO is rich in total flavonoids, polyphenols and saponins. Treatments with AG and ER SDEO significantly (p < 0.05) increased IL-5/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, suggesting that both AG and ER SDEO have the Th2-polarization property and anti-inflammatory potential. In addition, AG and ER SDEO, particularly ER SDEO, markedly decreased TNF-α/IL-10 secretion ratios by macrophages in the absence or presence of lipopolysaccharide (LPS), exhibiting substantial effects on spontaneous and LPS-induced inflammation. Significant correlations were found between the total polyphenols, flavonoids or saponins content in the two selected SDEOs and Th1/Th2 immune balance or anti-inflammatory ability in linear, non-linear or biphasic manners, respectively. In conclusion, our results suggest that AG and ER, particularly ER, SDEO have immunomodulatory potential in shifting the Th1/Th2 balance toward Th2 polarization in splenocytes and inhibiting inflammation in macrophages in the absence or presence of LPS.
Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands
Authors: Ishikawa Yasuko , Pieczonka Tomasz D , Bragiel-Pieczonka Aneta M , Seta Harumichi , Ohkuri Tadahiro , Sasanuma Yumi , Nonaka Yuji
Published: February 2020

Xerostomia, also known as dry mouth, is caused by a reduction in salivary secretion and by changes in the composition of saliva associated with the malfunction of salivary glands. Xerostomia decreases quality of life. In the present study, we investigated the effects of peptides derived from β-lactoglobulin C on age-dependent atrophy, gene expression profiles, and the dysfunction of salivary glands. Long-term oral administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK) and His59-Lys60 (HK) peptides induced salivary secretion and prevented and/or reversed the age-dependent atrophy of salivary glands in older rats. The transcripts of 78 genes were upregulated and those of 81 genes were downregulated by more than 2.0-fold (p ≤ 0.05) after LHK treatment. LHK upregulated major salivary protein genes such as proline-rich proteins (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatins (Cst5, Cyss, Vegp2), amylases (Amy1a, Amy2a3), and lysozyme (Lyzl1), suggesting that LLHK, LHK, and HK restored normal salivary function. The AP-2 transcription factor gene (Tcfap2b) was also induced significantly by LHK treatment. These results suggest that LLHK, LHK, and HK-administration may prevent and/or reverse the age-dependent atrophy and functional decline of salivary glands by affecting gene expression.
Correlations between Microbiota Bioactivity and Bioavailability of Functional Compounds: A Mini-Review
Authors: Vamanu Emanuel , Gatea Florentina
Published: February 2020

Numerous studies have demonstrated the role of the microbiota in supporting the physiological functions, owing to its metabolomic component. The presence of biocomponents generally leads to the correction of the microbial pattern correlated with the reduction of oxidative pressure. This study aims to present the main processes that correlate the bioavailability and bioactivity of some functional components through the action of the human microbiota. The use of probiotics and prebiotics is an innovative manner involving alternatives that increase the bioavailability of certain natural or metabolic components has been proposed. Probiotic strains (Saccharomyces cerevisiae or Lactobacillus (L.) plantarum) may represent an intermediary for increasing the antioxidant bioactivity, and they may be administered in the form of a biomass enriched with functional compounds, such as phenolic acids. The limiting effect of gastrointestinal transit is, in several cases, the key to the biopharmaceutical value of new products (or supplements). The identification of newer ways of formulating supplements also involves the compatibility of different types of products, the testing of bioaccessibility, and the elimination of biotransformations.
Influence of the Facets of Bi24O31Br10 Nanobelts and Nanosheets on Their Photocatalytic Properties
Authors: Zeng Qindan , Xie Wei , Chen Zhihong , Wang Xin , Akinoglu Eser Metin , Zhou Guofu , Shui Lingling
Published: February 2020

Bi24O31Br10 microcrystals composed of nanobelts and nanosheets with exposed (30-4) and (117) facets were synthesized by a simple hydrothermal method. The desired morphology and facets were obtained by adjusting the pH of the reaction system. Bi24O31Br10 nanobelts (BOB-NBs) with dominant (30-4) exposed facets were used for the photocatalytic degradation of tetracycline hydrochloride under visible light irradiation, with a degradation efficiency of up to 91% after 60 min of irradiation. The BOB-NBs possessed a higher charge separation and transfer efficiency, and showed less charge carrier recombination compared to the Bi24O31Br10 nanosheets (BOB-NSs), ascribed to a cooperative effect between the internal electric fields and surface active sites. A higher photocurrent response (2.6 times higher) was observed for BOB-NBs (12.8 μA cm−2) compared to that of BOB-NSs (4.9 μA cm−2). These findings are directional for a comprehensive understanding of the influence of the crystal facets of Bi24O31Br10 microcrystals on their photocatalytic activity and could help to guide the future design of high-performance photocatalytic materials.
Biocatalytic Synthesis of Calycosin-7-O-β-D-Glucoside with Uridine Diphosphate–Glucose Regeneration System
Authors: Hu Yumei , Min Jian , Qu Yingying , Zhang Xiao , Zhang Juankun , Yu Xuejing , Dai Longhai
Published: February 2020

Calycosin-7-O-β-D-glucoside (Cy7G) is one of the principal components of Radix astragali. This isoflavonoid glucoside is regarded as an indicator to assess the quality of R. astragali and exhibits diverse pharmacological activities. In this study, uridine diphosphate-dependent glucosyltransferase (UGT) UGT88E18 was isolated from Glycine max and expressed in Escherichia coli. Recombinant UGT88E18 could selectively and effectively glucosylate the C7 hydroxyl group of calycosin to synthesize Cy7G. A one-pot reaction by coupling UGT88E18 to sucrose synthase (SuSy) from G. max was developed. The UGT88E18–SuSy cascade reaction could recycle the costly uridine diphosphate glucose (UDPG) from cheap sucrose and catalytic amounts of uridine diphosphate (UDP). The important factors for UGT88E18–SuSy cascade reaction, including UGT88E18/SuSy ratios, different temperatures, and pH values, different concentrations of dimethyl sulfoxide (DMSO), UDP, sucrose, and calycosin, were optimized. We produced 10.5 g L−1 Cy7G in the optimal reaction conditions by the stepwise addition of calycosin. The molar conversion of calycosin was 97.5%, with a space–time yield of 747 mg L−1 h−1 and a UDPG recycle of 78 times. The present study provides a new avenue for the efficient and cost-effective semisynthesis of Cy7G and other valuable isoflavonoid glucosides by UGT–SuSy cascade reaction.
Surface-Modified Titanium Dioxide Nanofibers with Gold Nanoparticles for Enhanced Photoelectrochemical Water Splitting
Authors: Nguyen Van Nghia , Nguyen Minh Vuong , Nguyen Thi Hong Trang , Doan Minh Thuy , Ngoc Loan Le Thi , Janssens Ewald , Yadav Anupam , Lin Pin-Cheng , Nguyen Manh Son , Hoang Nhat Hieu
Published: February 2020

High-stability, high-efficiency, and low-cost solar photoelectrochemical (PEC) water splitting has great potential for hydrogen-energy applications. Here, we report on gold/titanium dioxide (Au/TiO2) nanofiber structures grown directly on a conductive indium tin oxide substrate, and used as photoelectrodes in PEC cells for hydrogen generation. The titanium dioxide nanofibers (TiO2 NFs) are synthesized using electrospinning, and are surface-modified by the deposition of gold nanoparticles (Au NPs) using a simple photoreduction method. The structure and morphology of the materials were characterized by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The surface plasmon resonance (SPR) of the Au NPs was investigated by ultraviolet-visible (UV-Vis) diffuse reflectance spectroscopy. The PEC properties of the as-prepared photoelectrodes were measured. The obtained photoconversion efficiency of 0.52% under simulated-sunlight illumination by a 150 W xenon lamp of the Au/TiO2 NFs structure with 15 min UV irradiation for Au NP deposition was the highest value from comparable structures. Working photoelectrode stability was tested, and the mechanism of the enhanced PEC performance is discussed.
Effect of Structure on the Thermal-Mechanical Performance of Fully Ceramic Microencapsulated Fuel
Authors: Zhou Yi , Xiao Zhong , Liu Shichao , Chen Ping , Pang Hua , Xin Yong , Jiao Yongjun , Gao Shixin , Zhang Kun , Li Wenjie , Yu Junchong
Published: February 2020

The effect of non-fuel part size on the thermal-mechanical performance of fully ceramic microencapsulated (FCMTM) Fuel was investigated, and the non-fuel part size was selected according to integrity maintaining of non-fuel part and silicon carbide (SiC) layers. The non-fuel part size can affect the FCMTM temperature and stress distribution greatly by changing the distance between tristructural isotropic (TRISO) particles. The maximum temperature of SiC matrix increased from 1220 K to 1450 K with the non-fuel part size increasing from 100 μm to 500 μm, and the matrix temperature of all the samples was lower than the decomposition point of SiC ceramics. The maximum hoop stress decreased with non-fuel part size, but the inner part exhibiteda crosscurrent trend. The inner part of the SiC matrix lost structure integrity because of the large hoop stress caused by the deformation of TRISO particles, however, the non-fuel parts of FCMTM pellet may maintain their integrity when the non-fuel part size was larger than 300 μm. SiC layers hoop stress increased with non-fuel part size, and the failure probability of SiC layer was lower than 2.2 × 10−4 for the FCMTM pellet with small non-fuel part size. The integrity of non-fuel and SiC layers can be maintained for the FCMTM pellet with the non-fuel part size from 300 μm to 400 μm.
Side-Chain Liquid Crystal Co-Polymers for Angular Photochromic Anti-Counterfeiting Powder and Fiber
Authors: Gao Yanzi , Feng Ke , Zhang Jin , Zhang Lanying
Published: February 2020

Anti-counterfeiting technologies with the features of easy distinguishability, high cost performance, and good processability are needed to meet the demands of a market during the consumption upgrading moment. A series of side-chain liquid crystal co-polymers (SCLCPs) are designed, synthesized, and blended, and the preparation of a series of angular photochromic materials that have different center reflection wavelengths in the visible and near infra-red region is reported in this article. Differential scanning calorimetry and polarized optical microscopy were utilized to characterize the phase transition behaviors and self-assembling structures of the SCLCPs. The selective reflection properties were characterized with a UV/VIS/IR spectrum study and further verified by scanning electron microscopy. The results showed that the SCLCPs had the desired reflection wavelengths and thermal stability. The SCLCPs could easily form a planar texture of cholesteric liquid crystal and, depending on the good processability, anti-counterfeiting powders and fibers with angular photochromic features were prepared and characterized to prove the potential applications of the SCLCPs in anti-counterfeiting labels.
Modeling Morquio A Syndrome: An Anthropometric Study of Body Characteristics and Stature
Authors: Różdżyńska-Świątkowska Agnieszka , Szklanny Krzysztof , Marucha Jolanta , Tylki-Szymańska Anna
Published: February 2020

Background: Morquio A syndrome or mucopolysaccharidosis (MPS) IVA is an autosomal recessive, life-limiting lysosomal storage disease caused by deficient activity of the enzyme galactosamine-6-sulfatase. Common early symptoms such as abnormalities of body stature can facilitate timely diagnosis. This study aimed to create a pattern of face and body stature based on anthropometric measurements taken from a cohort of Polish patients with MPS IVA. Methods: Analysis of 11 somatometric and 14 craniofacial features was performed on 20 patients with MPS IVA, aged from 3 months to 26 years. The diagnosis of MPS IVA was confirmed by enzymatic and molecular analysis. Two-tailed t-tests were used to compare mean values for body length and weight at birth between the MPS IVA patients and the general population. To show the degree and direction of deviation z-scores were calculated and then used to construct a model of an average MPS IVA patient. Results: Mean values for body height and weight at birth were greater for boys than for the general population. The observed pattern of head and body shape indicated that dwarfism occurred with age as a result of the relatively short trunk and lower limbs. Skeletal abnormalities included a bell-shaped chest with the ratio of chest depth to chest width being significantly above the norm. The head and neck were relatively elongated, in comparison to body height, and tucked between narrow shoulders. The head had dolichocephalic shape, while the nose was short with wide nostrils. Conclusions: Multiple anthropometric measurements, including age ranges, allowed for the creation of a model that showed the most characteristic features of the MPS IVA phenotype.
Diagnostic Problems in Diffuse Axonal Injury
Authors: Jang Sung Ho
Published: February 2020

In this study, three problems associated with diagnosing diffuse axonal injury (DAI) in patients with traumatic brain injury are reviewed: the shortage of scientific evidence supporting the 6-hour loss of consciousness (LOC) diagnostic criterion to discriminate concussion and DAI, the low sensitivity of conventional brain MRI in the detection of DAI lesions, and the inappropriateness of the term diffuse in DAI. Pathological study by brain biopsy is required to confirm DAI; however, performing a brain biopsy for the diagnosis of DAI in a living patient is impossible. Therefore, the diagnosis of DAI in a living patient is clinically determined based on the duration of LOC, clinical manifestations, and the results of conventional brain MRI. There is a shortage of scientific evidence supporting the use of the 6-hour LOC criterion to distinguish DAI from concussion, and axonal injuries have been detected in many concussion cases with a less than 6-hour LOC. Moreover, due to the low sensitivity of conventional brain MRI, which can only detect DAI lesions in approximately half of DAI patients, diagnostic MRI criteria for DAI are not well established. In contrast, diffusion tensor imaging (DTI) has been shown to have high sensitivity for the detection of DAI lesions. As DTI is a relatively new method, further studies aimed at the establishment of diagnostic criteria for DAI detection using DTI are needed. On the other hand, because DAI distribution is not diffuse but multifocal, and because axonal injury lesions have been detected in concussion patients, steps to standardize the use of terms related to axonal injury in both concussion and DAI are necessary.
Predictive Model of Clinical Attachment Loss and Oral Health-Related Quality of Life through Depressive Symptomatology, Oral Hygiene Habits, and Proinflammatory Biomarkers: A Pilot Study
Authors: Rodríguez Franco Norma Idalia , Moral de la Rubia José , Alcázar Pizaña Andrea Guadalupe
Published: February 2020

Subjective aspects such as oral health-related quality of life (OHRQoL) and depression are important aspects in the periodontal care. The objectives of the study were to test a predictive model of clinical attachment loss and OHRQoL in a pooled sample of dental patients with periodontitis and mental health patients with depressive symptomatology, and test the invariance of the model across both types of patients. Three self-report scales were applied to assess depression, OHRQoL and oral hygiene habits, saliva samples were collected for three proinflammatory biomarkers, and the clinical attachment loss was measured in 35 patients with periodontitis and 26 patients with depressive symptomatology. Data were analyzed through structural equation modeling. The one-group analysis revealed a psychosomatic complaint model of disagreement between the complaint and the clinically observable. In the multi-group analysis, the model was not invariant. It was necessary to introduce a singularity in relation to depressive symptomatology for each population. Thus, a good and equivalent fit was achieved between the six nested models in constraints, as well as equivalent parameters between both types of patients. The study of a dental population in conjunction with a mental health population with a psychosomatic risk factor reveals interesting and unexpected results.
Primary Stability of Three Different Osteotomy Techniques in Medullary Bone: An in Vitro Study
Authors: Attanasio Ferdinando , Antonelli Alessandro , Brancaccio Ylenia , Averta Fiorella , Figliuzzi Michele Mario , Fortunato Leonzio , Giudice Amerigo
Published: February 2020

Background: The aim of this in vitro study was to analyse the primary stability of 20 implants placed with Twist drills (TD) versus 20 implants placed with Summers osteotomes (SO) and 20 implants placed with B&B bone compactors (BC) in medullary bone (quality type III and type IV). Methods: The implants were placed in 10 fresh pig ribs fixed on a bench vice in order to avoid micro-movements during surgical procedures and measure recording. Peak insertion torque (PIT) and Peak removal torque (PRT) were recorded with MGT-12 digital torque gauge and ISQ was recorded through OSSTELL ISQ™ device by an independent operator. Results: Comparing our data (Tukey test p = 0.05), it was evidenced a statistically significant difference in the PIT between TD and BC groups (p = 0.01). Analysing ISQ data, there was a statistically significant difference between the TD and BC groups (p = 0.0001) and between the SO and BC groups (p = 0.014). The analysis of PRT evidenced a statistically significant difference between the TD and BC groups (p = 0.038). Conclusions: This study evidenced that bone compactor preparation can positively influence primary implant stability (PS), however further in vivo studies and a larger sample are necessary to assess the usefulness in several clinical settings.
Complexity Analysis of EEG, MEG, and fMRI in Mild Cognitive Impairment and Alzheimer’s Disease: A Review
Authors: Sun Jie , Wang Bin , Niu Yan , Tan Yuan , Fan Chanjuan , Zhang Nan , Xue Jiayue , Wei Jing , Xiang Jie
Published: February 2020

Alzheimer’s disease (AD) is a degenerative brain disease with a high and irreversible incidence. In recent years, because brain signals have complex nonlinear dynamics, there has been growing interest in studying complex changes in the time series of brain signals in patients with AD. We reviewed studies of complexity analyses of single-channel time series from electroencephalogram (EEG), magnetoencephalogram (MEG), and functional magnetic resonance imaging (fMRI) in AD and determined future research directions. A systematic literature search for 2000–2019 was performed in the Web of Science and PubMed databases, resulting in 126 identified studies. Compared to healthy individuals, the signals from AD patients have less complexity and more predictable oscillations, which are found mainly in the left parietal, occipital, right frontal, and temporal regions. This complexity is considered a potential biomarker for accurately responding to the functional lesion in AD. The current review helps to reveal the patterns of dysfunction in the brains of patients with AD and to investigate whether signal complexity can be used as a biomarker to accurately respond to the functional lesion in AD. We proposed further studies in the signal complexities of AD patients, including investigating the reliability of complexity algorithms and the spatial patterns of signal complexity. In conclusion, the current review helps to better understand the complexity of abnormalities in the AD brain and provide useful information for AD diagnosis.
Assessment of Structural Performance and Integrity for Vibration-based Energy Harvester in Frequency Domain
Authors: Jin Ji-Won , Kang Ki-Weon
Published: February 2020

A vibration-based energy harvester (VEH) utilizes vibrations originated from various structures and specifically maximizes the displacement of its moving parts, using the resonance between the frequency of external vibration loads from the structure and the natural frequency of VEH to improve power production efficiency. This study presents the procedure to evaluate the structural performance and structural integrity of VEH utilized in a railway vehicle under frequency domain. First of all, a structural performance test was performed to identify the natural frequency and assess the structural response in frequency domain. Then, the static structural analysis was carried out using FE analysis to investigate the failure critical locations (FCLs) and effect of resonance. Finally, we conducted a frequency response analysis to identify the structural response and investigate the structural integrity in frequency domain. Based on these results, the authors assessed the structural performance and integrity of VEHs in two versions.