bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Immunoglobulin Therapy Eliminates Candida albicans and Maintains Intestinal Homeostasis in a Murine Model of Dextran Sulfate Sodium-Induced Colitis
Authors: Charlet Rogatien , Sendid Boualem , Kaveri Srini V. , Poulain Daniel , Bayry Jagadeesh , Jawhara Samir
Published: March 2019

Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine interleukin (IL)-6 and enhancement of IL-10 in the gut. IVIg therapy also led to an increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), while toll-like receptor 4 (TLR-4) expression was reduced. IVIg treatment reduces intestinal inflammation in mice and eliminates C. albicans overgrowth from the gut in association with down-regulation of pro-inflammatory mediators combined with up-regulation of anti-inflammatory cytokines.
Psoriasis Pathogenesis and Treatment
Authors: Rendon Adriana , Schäkel Knut
Published: March 2019

Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
Curcumin: A Potent Protectant against Esophageal and Gastric Disorders
Authors: Kwiecien Slawomir , Magierowski Marcin , Majka Jolanta , Ptak-Belowska Agata , Wojcik Dagmara , Sliwowski Zbigniew , Magierowska Katarzyna , Brzozowski Tomasz
Published: March 2019

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett’s esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.
Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis
Authors: Baj Andreina , Moro Elisabetta , Bistoletti Michela , Orlandi Viviana , Crema Francesca , Giaroni Cristina
Published: March 2019

A complex bidirectional communication system exists between the gastrointestinal tract and the brain. Initially termed the “gut-brain axis” it is now renamed the “microbiota-gut-brain axis” considering the pivotal role of gut microbiota in maintaining local and systemic homeostasis. Different cellular and molecular pathways act along this axis and strong attention is paid to neuroactive molecules (neurotransmitters, i.e., noradrenaline, dopamine, serotonin, gamma aminobutyric acid and glutamate and metabolites, i.e., tryptophan metabolites), sustaining a possible interkingdom communication system between eukaryota and prokaryota. This review provides a description of the most up-to-date evidence on glutamate as a neurotransmitter/neuromodulator in this bidirectional communication axis. Modulation of glutamatergic receptor activity along the microbiota-gut-brain axis may influence gut (i.e., taste, visceral sensitivity and motility) and brain functions (stress response, mood and behavior) and alterations of glutamatergic transmission may participate to the pathogenesis of local and brain disorders. In this latter context, we will focus on two major gut disorders, such as irritable bowel syndrome and inflammatory bowel disease, both characterized by psychiatric co-morbidity. Research in this area opens the possibility to target glutamatergic neurotransmission, either pharmacologically or by the use of probiotics producing neuroactive molecules, as a therapeutic approach for the treatment of gastrointestinal and related psychiatric disorders.
Targeting the ERK Signaling Pathway in Melanoma
Authors: Savoia Paola , Fava Paolo , Casoni Filippo , Cremona Ottavio
Published: March 2019

The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era in the treatment of this tumor. Vemurafenib was the first specific kinase inhibitor approved for therapy of advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib and encorafenib. However, despite the excellent results of first-generation kinase inhibitors in terms of response rate, the average duration of the response was short, due to the onset of genetic and epigenetic resistance mechanisms. The combination therapy with MEK inhibitors is an excellent strategy to circumvent drug resistance, with the additional advantage of reducing side effects due to the paradoxical reactivation of the MAPK pathway. The recent development of RAS and extracellular signal-related kinases (ERK) inhibitors promises to add new players for the ultimate suppression of this signaling pathway and the control of pathway-related drug resistance. In this review, we analyze the pharmacological, preclinical, and clinical trial data of the various MAPK pathway inhibitors, with a keen interest for their clinical applicability in the management of advanced melanoma.
Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice
Authors: Duong Quoc-Viet , Kintzing Margia L. , Kintzing William E. , Abdallah Ihab M. , Brannen Andrew D. , Kaddoumi Amal
Published: March 2019

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting 5.4 million people in the United States. Currently approved pharmacologic interventions for AD are limited to symptomatic improvement, not affecting the underlying pathology. Therefore, the search for novel therapeutic strategies is ongoing. A hallmark of AD is the compromised blood-brain barrier (BBB); thus, developing drugs that target the BBB to enhance its integrity and function could be a novel approach to prevent and/or treat AD. Previous evidence has shown the beneficial effects of growth factors in the treatment of AD pathology. Based on reported positive results obtained with the product Endoret®, the objective of this study was to investigate the effect of plasma rich in growth factors (PRGF) on the BBB integrity and function, initially in a cell-based BBB model and in 5x Familial Alzheimer’s Disease (5xFAD) mice. Our results showed that while PRGF demonstrated a positive effect in the cell-based BBB model with the enhanced integrity and function of the model, the in-vivo findings showed that PRGF exacerbated amyloid pathology in 5xFAD brains. At 10 and 100% doses, PRGF increased amyloid deposition associated with increased apoptosis and neuroinflammation. In conclusion, our results suggest PRGF may not provide beneficial effects against AD and the consideration to utilize growth factors should further be investigated.
Horse Oil Mitigates Oxidative Damage to Human HaCaT Keratinocytes Caused by Ultraviolet B Irradiation
Authors: Piao Mei Jing , Kang Kyoung Ah , Zhen Ao Xuan , Kang Hee Kyoung , Koh Young Sang , Kim Bong Seok , Hyun Jin Won
Published: March 2019

Horse oil products have been used in skin care for a long time in traditional medicine, but the biological effects of horse oil on the skin remain unclear. This study was conducted to evaluate the protective effect of horse oil on ultraviolet B (UVB)-induced oxidative stress in human HaCaT keratinocytes. Horse oil significantly reduced UVB-induced intracellular reactive oxygen species and intracellular oxidative damage to lipids, proteins, and DNA. Horse oil absorbed light in the UVB range of the electromagnetic spectrum and suppressed the generation of cyclobutane pyrimidine dimers, a photoproduct of UVB irradiation. Western blotting showed that horse oil increased the UVB-induced Bcl-2/Bax ratio, inhibited mitochondria-mediated apoptosis and matrix metalloproteinase expression, and altered mitogen-activated protein kinase signaling-related proteins. These effects were conferred by increased phosphorylation of extracellular signal-regulated kinase 1/2 and decreased phosphorylation of p38 and c-Jun N-terminal kinase 1/2. Additionally, horse oil reduced UVB-induced binding of activator protein 1 to the matrix metalloproteinase-1 promoter site. These results indicate that horse oil protects human HaCaT keratinocytes from UVB-induced oxidative stress by absorbing UVB radiation and removing reactive oxygen species, thereby protecting cells from structural damage and preventing cell death and aging. In conclusion, horse oil is a potential skin protectant against skin damage involving oxidative stress.
Quantitative Assessment of the Learning Curve for Robotic Thyroid Surgery
Authors: Kim HyunGoo , Kwon Hyungju , Lim Woosung , Moon Byung-In , Paik Nam Sun
Published: March 2019

With the increased utilization of robot thyroidectomy in recent years, surgical proficiency is the paramount consideration. However, there is no single perfect or ideal method for measuring surgical proficiency. In this study, we evaluated the learning curve of robotic thyroidectomy using various parameters. A total of 172 robotic total thyroidectomies were performed by a single surgeon between March 2014 and February 2018. Cumulative summation analysis revealed that it took 50 cases for the surgeon to significantly improve the operation time. Mean operation time was significantly shorter in the group that included the 51st to the 172nd case, than in the group that included only the first 50 cases (132.8 ± 27.7 min vs. 166.9 ± 29.5 min; p < 0.001). On the other hand, the surgeon was competent after the 75th case when postoperative transient hypoparathyroidism was used as the outcome measure. The incidence of hypoparathyroidism gradually decreased from 52.0%, for the first 75 cases, to 40.2% after the 76th case. These results indicated that the criteria used to assess proficiency greatly influenced the interpretation of the learning curve. Incorporation of the operation time, complications, and oncologic outcomes should be considered in learning curve assessment.
Treatment of Liver Metastases from Midgut Neuroendocrine Tumours: A Systematic Review and Meta-Analysis
Authors: Kaçmaz Enes , Heidsma Charlotte M. , Besselink Marc G. H. , Dreijerink Koen M. A. , Klümpen Heinz-Josef , Nieveen van Dijkum Elisabeth J. M. , Engelsman Anton F.
Published: March 2019

Strong evidence comparing different treatment options for liver metastases (LM) arising from gastroenteropancreatic neuroendocrine tumours (GEP-NET) is lacking. The aim of this study was to determine which intervention for LMs from GEP-NETs shows the longest overall survival (OS). A systematic search was performed in MEDLINE, Embase and the Cochrane Library in February 2018. Studies reporting on patients with LMs of any grade of sporadic GEP-NET comparing two intervention groups were included for analysis. Meta-analyses were performed where possible. Eleven studies, with a total of 1108, patients were included; 662 patients had LM from pancreatic NETs (pNET), 164 patients from small-bowel NETs (SB-NET) and 282 patients of unknown origin. Improved 5-year OS was observed for surgery vs. chemotherapy (OR 0.05 95% CI [0.01, 0.21] p < 0.0001), for surgery vs. embolization (OR 0.18 95% CI [0.05, 0.61] p = 0.006) and for LM resection vs. no LM resection (OR 0.15 95% CI [0.05, 0.42] p = 0.0003). This is the largest meta-analysis performed comparing different interventions for LMs from GEP-NETs. Despite the high risk of bias and heterogeneity of data, surgical resection for all tumour grades results in the longest overall survival. Chemotherapy and embolization should be considered as an alternative in case surgery is not feasible.
High-Intensity Interval Training is Associated with Improved Long-Term Survival in Heart Failure Patients
Authors: Hsu Chih-Chin , Fu Tieh-Cheng , Yuan Shin-Sheng , Wang Chao-Hung , Liu Min-Hui , Shyu Yu-Chiau , Cherng Wen-Jin , Wang Jong-Shyan
Published: March 2019

This matched-control cohort study explored the effects of high-intensity interval training (HIIT) on left ventricle (LV) dimensions and survival in heart failure (HF) patients between 2009 and 2016. HF patients who underwent the multidisciplinary disease management program (MDP) were enrolled. Non-exercising participants, aged (mean (95% confidence interval)) 62.8 (60.1–65.5) years, were categorized as the MDP group (n = 101). Participants aged 61.5 (58.7–64.2) years who had completed 36 sessions of HIIT were treated as the HIIT group (n = 101). Peak oxygen consumption (VO2peak) and LV geometry were assessed during the 8-year follow-up period. The 5-year all-cause mortality risk factors and overall survival rates were determined in the longitudinal observation. An increased VO2peak of 14–20% was observed in the HIIT group after exercise training. Each 1-mL/kg/min increase in VO2peak conferred a 58% improvement in 5-year mortality. Increased LV end-systolic diameter (LVESD) was significantly (p = 0.0198) associated with increased mortality. The 8-month survival rate was significantly improved (p = 0.044) in HIIT participants compared to non-exercise participants. HF patients with VO2peak ≥14.0 mL/kg/min and LVESD <44 mm had a significantly better 5-year survival rate (98.2%) than those (57.3%) with lower VO2peak and greater LVESD. Both HIIT-induced increased VO2peak and decreased LVESD are associated with improved survival in HF patients.
Evolution of Guidelines for Testosterone Replacement Therapy
Authors: Park Hyun Jun , Ahn Sun Tae , Moon Du Geon
Published: March 2019

Testosterone is an essential hormone required for the developmental growth and maintenance of the male phenotype during the whole life. With the increasing male life expectancy worldwide and development of adequate testosterone preparations, the prescription of testosterone has increased tremendously. Testosterone replacement should be based on low serum testosterone and related clinical symptoms. In the last two decades, with the accumulation of data, official recommendations have evolved in terms of definition, diagnosis, treatment, and follow-up. In practice, it is better for physicians to follow the Institutional Official Recommendations or Clinical Practice Guideline for an adequate diagnosis and treatment of testosterone deficiency. Currently, four official recommendations are available for diagnosis and treatment of patients with testosterone deficiency. The inconsistencies in the guidelines merely create confusion among the physicians instead of providing clear information. Furthermore, there is no definite method to assess serum testosterone and clinical symptoms. In the era of active testosterone replacement therapy (TRT), physicians’ practice patterns should be consistent with the clinical practice guidelines to avoid the misuse of testosterone. In this review, the author introduces the evolution of clinical guidelines to provide a comprehensive understanding of the differences and controversies with respect to TRT.
Improved Performance of Graphene in Heat Dissipation when Combined with an Orientated Magnetic Carbon Fiber Skeleton under Low-Temperature Thermal Annealing
Authors: Li Jing , Lei Rubai , Lai Jinfeng , Chen Xuyang , Li Yang
Published: March 2019

The high thermal conductivity and stability, outstanding mechanical properties, and low weight make graphene suitable for many applications in the realm of thermal management, especially in high integration systems. Herein, we report a high-performance, low-temperature reduced graphene oxide/magnetic carbon fiber composite film. Magnetic carbon fibers were prepared using a co-precipitation method, and the graphene oxide solution was prepared using an improved Hummers’ method. The magnetic carbon fibers were orientated by magnetite and immersed in the graphene oxide solution during filtration, followed by annealing at 800 °C. The composite film exhibited improved thermal conductivity (over 600 W/m·K) and mechanical properties (tensile strength of 37.1 MPa and bending cycle of up to 8000). The experimental results illustrate that the graphene in the composite membrane provides heat transfer channels to promote in-plane thermal conductivity, while the magnetic carbon fiber acts as a scaffold to reinforce the mechanical properties and improve the quality of the graphene. Due to the synergistic effect of the graphene and magnetic carbon, this composite has wide potential applications in heat dissipation.
Degradation of Phenol Using Peroxymonosulfate Activated by a High Efficiency and Stable CoMgAl-LDH Catalyst
Authors: Liao Zhuwei , Zhu Jingyi , Jawad Ali , Muzi Jiajing , Chen Zhuqi , Chen Zhulei
Published: March 2019

In this study, we report on an active and stable CoMgAl layered double hydrotalcite (LDH) catalyst for phenol degradation by heterogeneous activation of peroxymonosulfate (PMS). The CoMgAl-LDH catalyst was synthesized by hydrothermal method. The PMS/CoMgAl-LDH system overcomes the drawbacks of traditional Fenton processes. Various effects, e.g., scavengers, chloride ion, catalyst dosage, PMS concentration, temperature, and pH, were also inspected to evaluate the system. The results indicated that the PMS/CoMgAl-LDH system had extremely high efficiency for phenol degradation; 0.1 mM phenol could be completely degraded by 0.3 g/L catalyst and 3 mM PMS within 60 min at 30 °C. The CoMgAl-LDH catalyst appeared to possess outstanding reusability and stability. After four rounds of recycling, nearly 100% of the phenol was removed within 80 min by the PMS/CoMgAl-LDH system, with only 0.05 mg/L Co2+ leaching. A sulfate radical was the main oxidation species in the PMS/Co-LDH system. The degradation rate of phenol was influenced by temperature, and the activation energy was 65.19 kJ/mol. These advantages proved the PMS/CoMgAl-LDH system is an effective strategy for the treatment of organic contaminants.
Influence of Porous Dressings Based on Butyric-Acetic Chitin Co-Polymer on Biological Processes In Vitro and In Vivo
Authors: Sujka Witold , Draczynski Zbigniew , Kolesinska Beata , Latanska Ilona , Jastrzebski Zenon , Rybak Zbigniew , Zywicka Boguslawa
Published: March 2019

In spite of intensively conducted research allowing for the development of more and more advanced wound dressing materials, there is still a need for dressings that stimulate not only reparative and regenerative processes, but also have a positive effect on infected and/or difficult-to-heal wounds. Porous dressing materials based on butyric-acetic chitin co-polyester containing 90% of butyryl and 10% of acetyl groups (BAC 90/10) can also be included in the group mentioned above. Two types of dressings were obtained by the salt leaching method, i.e. a porous sponge Medisorb R and Medisorb Ag with an antibacterial additive. The aim of the study was to evaluate biological effects of porous Medisorb R and Medisorb Ag dressings under in vitro and in vivo conditions. In an in vitro biodegradation test, no mass loss of Medisorb R dressing was observed within 14 days of incubation in physiological fluids at 37 °C. However, on the basis of the FTIR (Fourier Transform Infrared Spectroscopy) tests, surface degradation of Medisorb R dressing was observed. Additionally, the antibacterial activity of the porous Medisorb Ag dressing containing microsilver as an antibacterial additive was confirmed. The in vivo studies included inflammatory activity, skin irritation and sensitisation tests, as well an assessment of local effect after contact with subcutaneous tissue up to 6 months and skin wounds up to 21 days. In the in vivo tests, the dressings exhibited neither effects of skin irritation nor sensitisation. Under macroscopic examination, in full thickness defects of subcutaneous tissue and skin, the dressings caused wound healing with no inflammation, undergoing the most gradual biodegradation between weeks 4 and 8, and the observed differences were statistically significant. In the histological assessment, a weakened, limited inflammatory process associated with degradation of the material has been observed. The process of skin wound healing under Medisorb R dressing in the early period was accelerated compared to that observed in the control group with a gauze dressing.
Evaluation of Regression Models: Model Assessment, Model Selection and Generalization Error
Authors: Emmert-Streib Frank , Dehmer Matthias
Published: March 2019

When performing a regression or classification analysis, one needs to specify a statistical model. This model should avoid the overfitting and underfitting of data, and achieve a low generalization error that characterizes its prediction performance. In order to identify such a model, one needs to decide which model to select from candidate model families based on performance evaluations. In this paper, we review the theoretical framework of model selection and model assessment, including error-complexity curves, the bias-variance tradeoff, and learning curves for evaluating statistical models. We discuss criterion-based, step-wise selection procedures and resampling methods for model selection, whereas cross-validation provides the most simple and generic means for computationally estimating all required entities. To make the theoretical concepts transparent, we present worked examples for linear regression models. However, our conceptual presentation is extensible to more general models, as well as classification problems.
Use of 13C-qNMR Spectroscopy for the Analysis of Non-Psychoactive Cannabinoids in Fibre-Type Cannabis sativa L. (Hemp)
Authors: Marchetti Lucia , Brighenti Virginia , Rossi Maria Cecilia , Sperlea Johanna , Pellati Federica , Bertelli Davide
Published: March 2019

Cannabis sativa L. is a dioecious plant belonging to the Cannabaceae family. The discovery of the presence of many biologically-active metabolites (cannabinoids) in fibre-type Cannabis (hemp) has recently given rise to the valorisation of this variety. In this context, the present study was aimed at the multi-component analysis and determination of the main non-psychoactive cannabinoids (cannabidiol, cannabidiolic acid, cannabigerol and cannabigerolic acid) in female inflorescences of different hemp varieties by means of 13C quantitative nuclear magnetic resonance spectroscopy (qNMR). The method proposed here for the first time for the determination of cannabinoids provided reliable results in a competitive time with respect to the more consolidated HPLC technique. In fact, it gave sufficiently precise and sensitive results, with LOQ values lower than 750 μg/mL, which is easily achievable with concentrated extracts, without affecting the quality of 13C-qNMR spectra. In conclusion, this method can be considered as a promising and appropriate tool for the comprehensive chemical analysis of bioactive cannabinoids in hemp and other derived products in order to ensure their quality, efficacy and safety.
Improvement of Colonic Immune Function with Soy Isoflavones in High-Fat Diet-Induced Obese Rats
Authors: Luo Qihui , Cheng Dongjing , Huang Chao , Li Yifan , Lao Chengjie , Xia Yu , Liu Wentao , Gong Xiaoxia , Hu Danlei , Li Bin , He Xue , Chen Zhengli
Published: March 2019

Background: The damage to intestinal barrier function plays an important role in the development of obesity and associated diseases. Soy isoflavones are effective natural active components for controlling obesity and reducing the level of blood lipid. Here, we explored whether these effects of soy isoflavones were associated with the intestinal barrier function. Methods and Results: The obese rat models were established by high fat diet feeding. Then, those obese rats were supplemented with soy isoflavones at different doses for 4 weeks. Our results showed that obesity induced the expressions of pro-inflammatory cytokines, decreased the anti-inflammatory cytokine (IL-10) expression, elevated intestinal permeability, altered gut microbiota and exacerbated oxidative damages in colon. The administration of soy isoflavones reversed these changes in obese rats, presenting as the improvement of intestinal immune function and permeability, attenuation of oxidative damage, increase in the fraction of beneficial bacteria producing short-chain fatty acids and short-chain fatty acid production, and reduction in harmful bacteria. Furthermore, soy isoflavones blocked the expressions of TLR4 and NF-κB in the colons of the obese rats. Conclusions: Soy isoflavones could improve obesity through the attenuation of intestinal oxidative stress, recovery of immune and mucosal barrier, as well as re-balance of intestinal gut microbiota.
Catalytic Asymmetric Fluorination of Alkyl 1-indanone-2-carboxylates Ruled by Pybox-Eu(III) Combination
Authors: Granados Albert , Sarró Pau , Vallribera Adelina
Published: March 2019

A highly enantioselective catalytic method for the synthesis of quaternary α-fluoro derivatives of 3-oxo esters is described. The reaction uses europium (III) triflate and commercially available chiral pybox-type C2-symmetric ligand. Excellent results in terms of yields and enantioselectivities were assured using the electrophilic NFSI reagent under mild reaction conditions.
Ultrashort Echo Time Quantitative Susceptibility Mapping (UTE-QSM) of Highly Concentrated Magnetic Nanoparticles: A Comparison Study about Different Sampling Strategies
Authors: Lu Xing , Jang Hyungseok , Ma Yajun , Jerban Saeed , Chang Eric Y. , Du Jiang
Published: March 2019

The ability to accurately and non-invasively quantify highly concentrated magnetic nanoparticles (MNPs) is desirable for many emerging applications. Ultrashort echo time quantitative susceptibility mapping (UTE-QSM) has demonstrated the capability to detect high iron concentrations. In this study, we aimed to investigate the effect of different sampling trajectories on the accuracy of quantification based on MNPs acquired through UTE-QSM. A phantom with six different MNP concentrations was prepared for UTE-QSM study with different UTE sampling trajectories, including radial acquisition, continuous single point imaging (CSPI), and Cones with four different gradient stretching factors of 1.0, 1.2, 1.4, and 1.6. No significant differences were found in QSM values derived from the different UTE sampling strategies, suggesting that the UTE-QSM technique could be accelerated with extended Cones sampling.
Cu-Catalyzed Oxidative 3-Amination of Indoles via Formation of Indolyl(aryl)iodonium Imides Using o-Substituted (Diacetoxyiodo)arene as a High-Performance Hypervalent Iodine Compound
Authors: Watanabe Kazuhiro , Moriyama Katsuhiko
Published: March 2019

An oxidative 3-amination of indole derivatives using hypervalent iodine(III) and bissulfonimides, which proceeds via the formation of indolyl(aryl)iodonium imides, was developed. This reaction was followed by an indole-selective copper-catalyzed oxidative C–N coupling reaction to obtain 3-amino indole derivatives as single regioisomers. o-Alkoxy(diacetoxyiodo)arenes showed higher reactivity in the reaction than o-alkyl(diacetoxyiodo)arenes, efficiently promoting the formation of indolyl(aryl)iodonium imides in the first step.
Investigating the Formation of Structural Elements in Proteins Using Local Sequence-Dependent Information and a Heuristic Search Algorithm
Authors: Estaña Alejandro , Ghallab Malik , Bernadó Pau , Cortés Juan
Published: March 2019

Structural elements inserted in proteins are essential to define folding/unfolding mechanisms and partner recognition events governing signaling processes in living organisms. Here, we present an original approach to model the folding mechanism of these structural elements. Our approach is based on the exploitation of local, sequence-dependent structural information encoded in a database of three-residue fragments extracted from a large set of high-resolution experimentally determined protein structures. The computation of conformational transitions leading to the formation of the structural elements is formulated as a discrete path search problem using this database. To solve this problem, we propose a heuristically-guided depth-first search algorithm. The domain-dependent heuristic function aims at minimizing the length of the path in terms of angular distances, while maximizing the local density of the intermediate states, which is related to their probability of existence. We have applied the strategy to two small synthetic polypeptides mimicking two common structural motifs in proteins. The folding mechanisms extracted are very similar to those obtained when using traditional, computationally expensive approaches. These results show that the proposed approach, thanks to its simplicity and computational efficiency, is a promising research direction.
Phenylalkanoid Glycosides (Non-Salicinoids) from Wood Chips of Salix triandra × dasyclados Hybrid Willow
Authors: Noleto-Dias Clarice , Wu Yanqi , Bellisai Alice , Macalpine William , Beale Michael H. , Ward Jane L.
Published: March 2019

Salix triandra (almond leaved willow) is an established crop, grown in coppicing regimes for basket-making materials. It is known as a source of non-salicinoid phenolic glycosides, such as triandrin and salidroside. A spontaneous natural hybrid of S. triandra and S. dasyclados was subjected to metabolite profiling by high resolution LC-MS, and 22 phenolic glycosides, including 18 that are new to the Salicaceae, were identified. Structures were determined by HPLC isolation and NMR methods. The hybridisation process has introduced novel chemistry into the Salix phenolic glycoside palette, in particular, the ability to generate disaccharide conjugates where the glycosyl group is further extended by a range of sugars, including apiose, rhamnose, xylose, and arabinose. Also of note is the appearance of chavicol derivatives, also not previously seen in Salix spp. The work demonstrates the plasticity of the phenolic glycoside biosynthetic pathway, and the potential to improve established crops such as S. triandra and S. dasyclados, via high-value metabolites, for both basketry and bioenergy markets.
Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome
Authors: Liu Ting , Zeng Qingxuan , Zhao Xiaoqiang , Wei Wei , Li Yinghong , Deng Hongbin , Song Danqing
Published: March 2019

Twenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1β release at both cell and protein levels at the concentration of 5 μM. Among them, compound 6 exhibited promising inhibitory potency against IL-β activation with an IC50 value of 3.7 μM. Preliminary mechanism study revealed that 6 might target NLRP3 protein, and then block ASC pyroptosome formation with-NLRP3, rather than acting on the activation of the NLRP3 inflammasome (NF-κB and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound 6 against IL-β activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.
Purification and Structural Analysis of the Effective Anti-TMV Compound ε-Poly-l-lysine Produced by Streptomyces ahygroscopicus
Authors: Chen Jianguang , Liu He , Xia Zihao , Zhao Xiuxiang , Wu Yuanhua , An Mengnan
Published: March 2019

Microbial secondary metabolites produced by actinomycetes are important natural products widely applied to control plant diseases. A variety of actinomycetes were isolated from soil samples collected from Tianzhu Mountain in Shenyang, China. A Streptomyces strain Shenyang Tianzhu (STZ) exhibits effective antiviral activity against Tobacco mosaic virus (TMV). The isolate was identified as Streptomyces ahygroscopicus based on its cultural, morphological, physiological, biochemical characteristics as well as the phylogenetic analysis using 16S rRNA sequences. To obtain the pure anti-TMV compound from Streptomyces STZ, the culture broth was subjected to Amberlite IRC-50 ion-exchange resin, SX-8 macroporous adsorption resin and Sephadex G-25 gel column chromatography. The purified active compound was confirmed to be ε-poly-l-lysine (ε-PL), with molecular mass in the range of 3454–4352 Da by structural analysis with infrared (IR), matrix-assisted laser desorption ionization-time-of-flight MS (MALDI-TOF), thin-layer chromatography (TLC) and high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR). The protective and curative effects of the purified compound ε-PL were tested and the results showed that the compound exhibited significant protective and curative activity against TMV. The potential application of ε-PL as an efficient anti-plant virus agent was expected.
Evaluation of the Anti-Trypanosomal Activity of Vietnamese Essential Oils, with Emphasis on Curcuma longa L. and Its Components
Authors: Le Thanh Binh , Beaufay Claire , Nghiem Duc Trong , Pham Tuan Anh , Mingeot-Leclercq Marie-Paule , Quetin-Leclercq Joëlle
Published: March 2019

Human African trypanosomiasis (HAT), known as sleeping sickness and caused by Trypanosoma brucei, is threatening low-income populations in sub-Saharan African countries with 61 million people at risk of infection. In order to discover new natural products against HAT, thirty-seven Vietnamese essential oils (EOs) were screened for their activity in vitro on Trypanosoma brucei brucei (Tbb) and cytotoxicity on mammalian cells (WI38, J774). Based on the selectivity indices (SIs), the more active and selective EOs were analyzed by gas chromatography. The anti-trypanosomal activity and cytotoxicity of some major compounds (isolated or commercial) were also determined. Our results showed for the first time the selective anti-trypanosomal effect of four EOs, extracted from three Zingiberaceae species (Curcuma longa, Curcuma zedoaria, and Zingiber officinale) and one Lauraceae species (Litsea cubeba) with IC50 values of 3.17 ± 0.72, 2.51 ± 1.08, 3.10 ± 0.08, and 2.67 ± 1.12 nL/mL respectively and SI > 10. Identified compounds accounted for more than 85% for each of them. Among the five major components of Curcuma longa EO, curlone is the most promising anti-trypanosomal candidate with an IC50 of 1.38 ± 0.45 µg/mL and SIs of 31.7 and 18.2 compared to WI38 and J774 respectively.
Ecological Insights to Track Cytotoxic Compounds among Maytenus ilicifolia Living Individuals and Clones of an Ex Situ Collection
Authors: Pavarini Daniel Petinatti , Selegato Denise Medeiros , Castro-Gamboa Ian , do Sacramento Luiz Vitor Silva , Furlan Maysa
Published: March 2019

Biodiversity is key for maintenance of life and source of richness. Nevertheless, concepts such as phenotype expression are also pivotal to understand how chemical diversity varies in a living organism. Sesquiterpene pyridine alkaloids (SPAs) and quinonemethide triterpenes (QMTs) accumulate in root bark of Celastraceae plants. However, despite their known bioactive traits, there is still a lack of evidence regarding their ecological functions. Our present contribution combines analytical tools to study clones and individuals of Maytenus ilicifolia (Celastraceae) kept alive in an ex situ collection and determine whether or not these two major biosynthetic pathways could be switched on simultaneously. The relative concentration of the QMTs maytenin (1) and pristimerin (2), and the SPA aquifoliunin E1 (3) were tracked in raw extracts by HPLC-DAD and 1H-NMR. Hierarchical Clustering Analysis (HCA) was used to group individuals according their ability to accumulate these metabolites. Semi-quantitative analysis showed an extensive occurrence of QMT in most individuals, whereas SPA was only detected in minor abundance in five samples. Contrary to QMTs, SPAs did not accumulate extensively, contradicting the hypothesis of two different biosynthetic pathways operating simultaneously. Moreover, the production of QMT varied significantly among samples of the same ex situ collection, suggesting that the terpene contents in root bark extracts were not dependent on abiotic effects. HCA results showed that QMT occurrence was high regardless of the plant age. This data disproves the hypothesis that QMT biosynthesis was age-dependent. Furthermore, clustering analysis did not group clones nor same-age samples together, which might reinforce the hypothesis over gene regulation of the biosynthesis pathways. Indeed, plants from the ex situ collection produced bioactive compounds in a singular manner, which postulates that rhizosphere environment could offer ecological triggers for phenotypical plasticity.
Antibacterial and Biofilm Inhibitory Activity of Medicinal Plant Essential Oils Against Escherichia coli Isolated from UTI Patients
Authors: Lagha Rihab , Ben Abdallah Fethi , AL-Sarhan Badriah Osama , Al-Sodany Yassin
Published: March 2019

Urinary tract infections (UTIs), caused by Escherichia coli 80% to 85% of the time, are one of the most important causes of morbidity and health care spending affecting persons of all ages. These infections lead to many difficult problems, especially increasing resistance to antibiotic drugs. Bacterial biofilms play an important role in UTIs, responsible for persistent infections leading to recurrences and relapses. In this study, we have investigated the antibacterial activity of five medicinal plant essential oils against UTIs caused by E. coli using disc diffusion and minimal inhibition concentration (MIC) methods. In addition, biofilm inhibitory action of oils was realized by crystal violet. Gas chromatography–mass spectrometry (GC–MS) analysis showed a variability between oils in terms of compound numbers as well as their percentages. Antibacterial activity was observed only in cases of Origanum majorana, Thymus zygis and Rosmarinus officinalis, while Juniperus communis and Zingiber officinale did not showed any effect towards E. coli isolates. T. zygis essential oil demonstrated the highest antibacterial activity against E. coli isolates, followed by O. majorana and R. officinalis. Further, oils showed high biofilm inhibitory action with a percentage of inhibition that ranged from 14.94% to 94.75%. R. officinalis oil had the highest antibiofilm activity followed by T. zygis and O. majorana. Accordingly, tested oils showed very effective antibacterial and antibiofilm activities against E. coli UTIs and can be considered as good alternative for antibiotics substitution.
Bactericidal and Anti-Biofilm Activity of Ethanol Extracts Derived from Selected Medicinal Plants against Streptococcus pyogenes
Authors: Wijesundara Niluni M. , Rupasinghe H. P. Vasantha
Published: March 2019

Background: There is a growing interest in medicinal plants which have been traditionally used for the treatment of human infections. This study assessed 14 ethanol extracts (EEs) on bacterial growth and biofilm formation of Streptococcus pyogenes. Methods: Constituent major phytochemicals in the extracts were identified using ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Micro-broth dilution and time-kill assays were used to determine antibacterial activities. Anti-biofilm activities were studied using MTT assay, and morphology of biofilms was observed by scanning electron microscopy (SEM). Transmission electron microscopy (TEM) was employed to visualize the ultra-cross section structure of bacteria treated with efficacious extracts. Results: Licorice root, purple coneflower flower, purple coneflower stem, sage leaves and slippery elm inner bark EEs were the most effective, with minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 62.5 μg/mL and 125 μg/mL, respectively. The minimum biofilm inhibitory concentration (MBIC) of extracts ranged from 31.5–250 μg/mL. Morphological changes were observed in treated biofilms compared to the untreated. The four most effective extracts exhibited the ability to induce degradation of bacterial cell wall and disintegration of the plasma membrane. Conclusion: We suggest that EEs of sage leaf and purple coneflower flower are promising candidates to be further investigated for developing alternative natural therapies for the management of streptococcal pharyngitis.
Determination of Urinary Pterins by Capillary Electrophoresis Coupled with LED-Induced Fluorescence Detector
Authors: Grochocki Wojciech , Buszewska-Forajta Magdalena , Macioszek Szymon , J. Markuszewski Michał
Published: March 2019

Urinary pterins have been found as potential biomarkers in many pathophysiological conditions including inflammation, viral infections, and cancer. However, pterins determination in biological samples is difficult due to their degradation under exposure to air, light, and heat. Besides, they occur at shallow concentration levels, and thus, standard UV detectors cannot be used without additional sample preconcentration. On the other hand, ultra-sensitive laser-induced fluorescence (LIF) detection can be used since pterins exhibit native fluorescence. The main factor that limits an everyday use of LIF detectors is its high price. Here, an alternative detector, i.e., light-emitted diode induced fluorescence (LEDIF) detector, was evaluated for the determination of pterins in urine samples after capillary electrophoresis (CE) separation. An optimized method was validated in terms of linearity range, limit of detection (LOD), limit of quantification (LOQ), intra- and interday precision and accuracy, sample stability in the autosampler, and sample stability during the freezing/thawing cycle. The obtained LOD (0.1 µM) and LOQ (0.3 µM) values were three-order of magnitude lower compared to UV detector, and two orders of magnitude higher compared to previously reported house-built LIF detector. The applicability of the validated method was demonstrated in the analysis of urine samples from healthy individuals and cancer patients.
Speciation of Chromium in Alkaline Soil Extracts by an Ion-Pair Reversed Phase HPLC-ICP MS Method
Authors: Leśniewska Barbara , Godlewska-Żyłkiewicz Beata
Published: March 2019

The aim of this work was to study by a hyphenated HPLC-ICP MS technique the chromium species released during alkaline extraction of various soils collected from a contaminated area of an old tannery. An ultrasound-assisted extraction procedure using 0.1 mol L−1 Na2CO3 solution was developed for the release of chromium species from the soil. The chromium species in the soil extracts were separated on a C8 column using EDTA and TBAH solution as a mobile phase. The use of an ICP-QQQ MS spectrometer in tandem mass configuration (MS/MS) combined with an octopole reaction system (ORS3) pressurized with helium allows one to eliminate spectral interferences during Cr determination in the soil extracts. The detection limit of the procedure was 0.08 µg L−1 for Cr(III) and 0.09 µg L−1 for Cr(VI) species. The trueness of the IP RP HPLC-ICP MS method was proved by an analysis of CRM 041 and CRM 060. The advantage of the proposed method is the analysis of soil extracts without their preliminary neutralization, which limits the losses of Cr(VI) due to the reduction process. The analysed soils mainly contained chromium in immobile forms (94.6–98.5% of the total Cr content). In all alkaline soil extracts mostly the Cr(VI) form was found, but in the extract of organic soils Cr(III) was also present. This arose from the reduction of Cr(VI) species by organic matter (humic acids) and Fe(II). The amount of formed Cr(III) species was dependent on the type of soil (content of organic matter, Mn and Fe) and its moistness. For the first time, the presence of neutral and non-polar chromium fractions in the soil extracts was also demonstrated. It was found that reliable speciation analysis results could be obtained for mineral soils.
Halogen-Substituted Triazolethioacetamides as a Potent Skeleton for the Development of Metallo-β-Lactamase Inhibitors
Authors: Zhang Yilin , Yan Yong , Liang Lufan , Feng Jie , Wang Xuejun , Li Li , Yang Kewu
Published: March 2019

Metallo-β-lactamases (MβLs) are the target enzymes of β-lactam antibiotic resistance, and there are no effective inhibitors against MβLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MβLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032–15.64 μM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 μM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 μM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27μM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.