bluuebunny/crossref_metadata_2025 huggingface dataset:
Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK
Authors: Huang Qi , Wang Ting , Yang Liu , Wang He-Yao
Published: May 2017

Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.
SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy
Authors: Kawanami Daiji , Matoba Keiichiro , Takeda Yusuke , Nagai Yosuke , Akamine Tomoyo , Yokota Tamotsu , Sango Kazunori , Utsunomiya Kazunori
Published: May 2017

Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium–glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction. Renoprotection by SGLT2 inhibitors has been demonstrated in T2D patients with a high cardiovascular risk in randomized controlled trials (RCTs). These favorable effects of SGLT2 inhibitors are explained by several potential mechanisms, including the attenuation of glomerular hyperfiltration, inflammation and oxidative stress. In this review article, we discuss the renoprotective effects of SGLT2 inhibitors by integrating experimental findings with the available clinical data.
Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction
Authors: Desai Pujan , Tseng Hubert , Souza Glauco
Published: May 2017

There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces. With this platform, spheroids can be rapidly assembled and easily handled, while replicating native liver function. We assembled spheroids of primary human hepatocytes in a 384-well format and maintained this culture over five days, including a 72 h induction period with known CYP450 inducers/inhibitors. CYP450 activity and viability in the spheroids were assessed and compared in parallel with monolayers. CYP450 activity was induced/inhibited in spheroids as expected, separate from any toxic response. Spheroids showed a significantly higher baseline level of CYP450 activity and induction over monolayers. Positive staining in spheroids for albumin and multidrug resistance-associated protein (MRP2) indicates the preservation of hepatocyte function within spheroids. The study presents a proof-of-concept for the use of magnetic 3D cell culture for the assembly and handling of novel hepatic tissue models.
The Lys-Asp-Tyr Triad within the Mite Allergen Der p 1 Propeptide Is a Critical Structural Element for the pH-Dependent Initiation of the Protease Maturation
Authors: Chevigné Andy , Campizi Vincenzo , Szpakowska Martyna , Bourry David , Dumez Marie-Eve , Martins José , Matagne André , Galleni Moreno , Jacquet Alain
Published: May 2017

The major house dust mite allergen, Der p 1, is a papain-like cysteine protease expressed as an inactive precursor, proDer p 1, carrying an N-terminal propeptide with a unique structure. The maturation of the zymogen into an enzymatically-active form of Der p 1 is a multistep autocatalytic process initiated under acidic conditions through conformational changes of the propeptide, leading to the loss of its inhibitory ability and its subsequent gradual cleavage. The aims of this study were to characterize the residues present in the Der p 1 propeptide involved in the initiation of the zymogen maturation process, but also to assess the impact of acidic pH on the propeptide structure, the activity of Der p 1 and the fate of the propeptide. Using various complementary enzymatic and structural approaches, we demonstrated that a structural triad K17p-D51p-Y19p within the N-terminal domain of the propeptide is essential for its stabilization and the sensing of pH changes. Particularly, the protonation of D51p under acidic conditions unfolds the propeptide through disruption of the K17p-D51p salt bridge, reduces its inhibition capacity and unmasks the buried residues K17p and Y19p constituting the first maturation cleavage site of the zymogen. Our results also evidenced that this triad acts in a cooperative manner with other propeptide pH-responsive elements, including residues E56p and E80p, to promote the propeptide unfolding and/or to facilitate its proteolysis. Furthermore, we showed that acidic conditions modify Der p 1 proteolytic specificity and confirmed that the formation of the first intermediate represents the limiting step of the in vitro Der p 1 maturation process. Altogether, our results provide new insights into the early events of the mechanism of proDer p 1 maturation and identify a unique structural triad acting as a stabilizing and a pH-sensing regulatory element.
Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells
Authors: Kim Kwang-Youn , Park Kwang-Il , Kim Sang-Hun , Yu Sun-Nyoung , Park Sul-Gi , Kim Young , Seo Young-Kyo , Ma Jin-Yeul , Ahn Soon-Cheol
Published: May 2017

Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells. Cell viability assay, Western blot, annexin V/propidium iodide assay, acridine orange (AO) staining, caspase-3 activity assay, reactive oxygen species (ROS) production, and mitochondrial membrane potential were assayed. Our data showed that salinomycin alters the sensitivity of prostate cancer cells to autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the salinomycin-induced apoptosis. Notably, salinomycin decreased phosphorylated of AKT and phosphorylated mammalian target of rapamycin (mTOR) in prostate cancer cells. Pretreatment with LY294002, an autophagy and PI3K inhibitor, enhanced the salinomycin-induced apoptosis by decreasing the AKT and mTOR activities and suppressing autophagy. However, pretreatment with PD98059 and SB203580, an extracellular signal-regulated kinases (ERK), and p38 inhibitors, suppressed the salinomycin-induced autophagy by reversing the upregulation of ERK and p38. In addition, pretreatment with N-acetyl-l-cysteine (NAC), an antioxidant, inhibited salinomycin-induced autophagy by suppressing ROS production. Our results suggested that salinomycin induces apoptosis, which was related to ROS-mediated autophagy through regulation of the PI3K/AKT/mTOR and ERK/p38 MAPK signaling pathways.
A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells
Authors: Royston Kendra , Udayakumar Neha , Lewis Kayla , Tollefsbol Trygve
Published: May 2017

With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells.
A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the Offspring
Authors: Contu Laura , Hawkes Cheryl
Published: May 2017

Globally, more than 20% of women of reproductive age are currently estimated to be obese. Children born to obese mothers are at higher risk of developing obesity, coronary heart disease, diabetes, stroke, and asthma in adulthood. Increasing clinical and experimental evidence suggests that maternal obesity also affects the health and function of the offspring brain across the lifespan. This review summarizes the current findings from human and animal studies that detail the impact of maternal obesity on aspects of learning, memory, motivation, affective disorders, attention-deficit hyperactivity disorder, autism spectrum disorders, and neurodegeneration in the offspring. Epigenetic mechanisms that may contribute to this mother–child interaction are also discussed.
Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades
Authors: Lee Hanwool , Baek Seung , Lee Jong , Kim Chulwon , Ko Jeong-Hyeon , Lee Seok-Geun , Chinnathambi Arunachalam , Alharbi Sulaiman , Yang Woong , Um Jae-Young , Sethi Gautam , Ahn Kwang
Published: May 2017

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.
Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives
Authors: Vitale Salvatore , Laganà Antonio , Capriglione Stella , Angioli Roberto , La Rosa Valentina , Lopez Salvatore , Valenti Gaetano , Sapia Fabrizio , Sarpietro Giuseppe , Butticè Salvatore , Tuscano Carmelo , Fanale Daniele , Tropea Alessandro , Rossetti Diego
Published: May 2017

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.
The Occurrence, Biosynthesis, and Molecular Structure of Proanthocyanidins and Their Effects on Legume Forage Protein Precipitation, Digestion and Absorption in the Ruminant Digestive Tract
Authors: Jonker Arjan , Yu Peiqiang
Published: May 2017

Forages grown in temperate regions, such as alfalfa (Medicago sativa L.) and white clover (Trefolium repens L.), typically have a high nutritional value when fed to ruminants. Their high protein content and degradation rate result, however, in poor utilization of protein from the forage resulting in excessive excretion of nitrogen into the environment by the animal. Proanthocyanindins (also known as condensed tannins) found in some forage legumes such as birdsfoot trefoil (Lotus corniculatus L.), bind to dietary protein and can improve protein utilization in the animal. This review will focus on (1) the occurrence of proanthocyanidins; (2) biosynthesis and structure of proanthocyanidins; (3) effects of proanthocyanidins on protein metabolism; (4) protein precipitating capacity of proanthocyanidins and their effects on true intestinal protein adsorption by ruminants; and (5) effect on animal health, animal performance and environmental emissions.
State of Art of Cancer Pharmacogenomics in Latin American Populations
Authors: López-Cortés Andrés , Guerrero Santiago , Redal María , Alvarado Angel , Quiñones Luis
Published: May 2017

Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations. In this review, we present the current status of research on somatic and germline alterations in Latin America compared to those found in Caucasian and Asian populations.
Dye-Sensitized Photocatalytic Water Splitting and Sacrificial Hydrogen Generation: Current Status and Future Prospects
Authors: Chowdhury Pankaj , Malekshoar Ghodsieh , Ray Ajay
Published: May 2017

Today, global warming and green energy are important topics of discussion for every intellectual gathering all over the world. The only sustainable solution to these problems is the use of solar energy and storing it as hydrogen fuel. Photocatalytic and photo-electrochemical water splitting and sacrificial hydrogen generation show a promise for future energy generation from renewable water and sunlight. This article mainly reviews the current research progress on photocatalytic and photo-electrochemical systems focusing on dye-sensitized overall water splitting and sacrificial hydrogen generation. An overview of significant parameters including dyes, sacrificial agents, modified photocatalysts and co-catalysts are provided. Also, the significance of statistical analysis as an effective tool for a systematic investigation of the effects of different factors and their interactions are explained. Finally, different photocatalytic reactor configurations that are currently in use for water splitting application in laboratory and large scale are discussed.
The Solvency II Standard Formula, Linear Geometry, and Diversification
Authors: Paulusch Joachim
Published: May 2017

The core of risk aggregation in the Solvency II Standard Formula is the so-called square root formula. We argue that it should be seen as a means for the aggregation of different risks to an overall risk rather than being associated with variance-covariance based risk analysis. Considering the Solvency II Standard Formula from the viewpoint of linear geometry, we immediately find that it defines a norm and therefore provides a homogeneous and sub-additive tool for risk aggregation. Hence, Euler’s Principle for the reallocation of risk capital applies and yields explicit formulas for capital allocation in the framework given by the Solvency II Standard Formula. This gives rise to the definition of diversification functions, which we define as monotone, subadditive, and homogeneous functions on a convex cone. Diversification functions constitute a class of models for the study of the aggregation of risk and diversification. The aggregation of risk measures using a diversification function preserves the respective properties of these risk measures. Examples of diversification functions are given by seminorms, which are monotone on the convex cone of non-negative vectors. Each L p norm has this property, and any scalar product given by a non-negative positive semidefinite matrix does as well. In particular, the Standard Formula is a diversification function and hence a risk measure that preserves homogeneity, subadditivity and convexity.
Ionanocarbon Lubricants. The Combination of Ionic Liquids and Carbon Nanophases in Tribology
Authors: Avilés María-Dolores , Saurín Noelia , Sanes José , Carrión Francisco-José , Bermúdez María-Dolores
Published: May 2017

The present overview will focus on the tribological applications of what we have called ionanocarbon lubricants, that is, the combination of carbon nanophases (graphene, carbon nanotubes, nanodiamonds, carbon nanodots) and room-temperature ionic liquids in new dispersions, blends, or modified nanostructures and their use in tribology, lubrication, and surface engineering as friction-reducing, antiwear, and surface-protecting agents in thin films and composite materials. Further research lines and factors that limit the practical applications of the outstanding research results are also highlighted. The very recent results in these lines of research make this a necessary brief review.
Hydrogels Synthesized by Electron Beam Irradiation for Heavy Metal Adsorption
Authors: Manaila Elena , Craciun Gabriela , Ighigeanu Daniel , Cimpeanu Catalina , Barna Catalina , Fugaru Viorel
Published: May 2017

Poly(acrylamide co-acrylic acid) hydrogels were prepared by free-radical copolymerization of acrylamide and acrylic acid in aqueous solutions using electron beam irradiation in the dose range of 2.5 kGy to 6 kGy in atmospheric conditions and at room temperature. The influence of the absorbed dose, the amount of cross-linker (trimethylolpropane trimethacrylate) and initiator (potassium persulfate) on the swelling properties and the diffusion coefficient and network parameters of hydrogels were investigated. The structure and morphology of hydrogels were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The use of the obtained hydrogels by the removal of Cu2+ and Cr6+ from aqueous solutions was investigated at room temperature. During the adsorption of metal ions on hydrogels, the residual metal ion concentration in the solution was measured by an atomic absorption spectrophotometer (AAS). It has been established that the use of a relatively small amount of trimethylolpropane trimethacrylate for hydrogel preparation has led to the increasing of swelling up to 8500%.
New Challenges in Tribology: Wear Assessment Using 3D Optical Scanners
Authors: Valigi Maria , Logozzo Silvia , Affatato Saverio
Published: May 2017

Wear is a significant mechanical and clinical problem. To acquire further knowledge on the tribological phenomena that involve freeform mechanical components or medical prostheses, wear tests are performed on biomedical and industrial materials in order to solve or reduce failures or malfunctions due to material loss. Scientific and technological advances in the field of optical scanning allow the application of innovative devices for wear measurements, leading to improvements that were unimaginable until a few years ago. It is therefore important to develop techniques, based on new instrumentations, for more accurate and reproducible measurements of wear. The aim of this work is to discuss the use of innovative 3D optical scanners and an experimental procedure to detect and evaluate wear, comparing this technique with other wear evaluation methods for industrial components and biomedical devices.
Cereus sinensis Polysaccharide and Its Immunomodulatory Properties in Human Monocytic Cells
Authors: Wu Junwen , Zhou Xuefei , Zhang Min , Yao Yun , Han Juanjuan , Liu Kehai
Published: May 2017

In this study, the extraction conditions of the crude polysaccharide from Cereus sinensis were optimized by response surface methodology. The optimum extraction conditions were: a ratio of raw material to water volume of 1:80 (g/mL); an extraction temperature of 72 °C; and an extraction time of 3 h. Then, a purified polysaccharide named Cereus sinensis polysaccharide-1 (CSP-1) was obtained from the crude polysaccharide by the Diethylaminoethyl cellulose-52 (DEAE-52) cellulose chromatography column and Sephadex G-100 column. The molecular weight and monosaccharide composition of CSP-1 was determined through Gel Permeation Chromatography (GPC) and Gas Chromatography–Mass Spectrometer (GS–MS), respectively. The results showed that CSP-1 with an average molecular weight of 56,335 Da was composed of l-(−)-Fucose, d-(+)-Mannose, d-Glucose and mainly possessed 1→2, 1→2, 6, 1→4, and 1→4, 6 of glycosyl linkages. The immunomodulatory activities of CSP-1 were also evaluated using lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. The results demonstrated that CSP-1 dose-dependently protected against LPS-induced toxicity, and CSP-1 significantly inhibited the Toll-like receptor 4 (TLR-4) mRNA, myeloid differentiation factor 88 (MyD88) mRNA and tumour necrosis factor receptor-associated factor-6 (TRAF-6) mRNA expression of the LPS-induced THP-1 cells, as well as suppressing reactive oxygen species (ROS) generation.
Antioxidant and Antimicrobial Activities of the Essential Oil of Achillea millefolium L. Grown in France
Authors: El-Kalamouni Chaker , Venskutonis Petras , Zebib Bachar , Merah Othmane , Raynaud Christine , Talou Thierry
Published: May 2017

Background: This study aimed to examine the composition of essential oil (EO) of A. millefolium aerial parts wild plant grown in France and evaluate its antioxidant, antibacterial, and antifungal activities. Methods: GC-MS was used to identify the chemical composition of EO. Antioxidant activity (AA) of EO was evaluated by Oxipres method. Antimicrobial activity of EO was evaluated by Agar-well diffusion and a broth microdilution assay. Results: Forty-three volatile compounds were identified. Major compounds were camphor (12.8%), germacrene-D (12%), (E)-nerolidol (7.3%), sabinene (6.7%), (E)-p-mentha-2,8-dien-1-ol (4.5%), and 1,8-cineole (4%). EO shows strong AA against Sunflower oil oxidation. Additionally, an inhibitory effect against microbial organisms (bacteria and fungi) was found. Conclusion: The EO composition of A. millefolium chemotype located in France was studied. The EO of the A. millefolium wild plant grown in France is quite an effective antioxidant in sunflower oil oxidation; it also possesses inhibitory effects against famous bacteria and fungi.
The Effect of Acupuncture on Visual Function in Patients with Congenital and Acquired Nystagmus
Authors: Blechschmidt Tilo , Krumsiek Maike , Todorova Margarita
Published: May 2017

Background: The aim of this study is to examine the short-term effect of visual function following acupuncture treatment in patients with congenital idiopathic nystagmus and acquired nystagmus (CIN and AN). Methods: An observational pilot study on six patients with confirmed diagnosis of nystagmus (three CIN and three AN patients (2♀, 4♂; mean age 42.67; SD ± 20.57 y)), was performed. Acupuncture treatment was done following a standardized protocol applying needle-acupuncture on the body and the ears. The treatment was scheduled with 10 sessions of 30 min duration over five weeks. To assess the effect of the treatment, we performed before, between, and after acupuncture objective measurement of the BCVA (EDTRS charts), contrast vision (CSV-1000, Vector Vision), nystagmography (Compact Integrated Pupillograph), complemented by evaluation questionnaires. A placebo non-acupuncture control group (Nr: 11, 22 eyes; 8♀, 3♂; mean age: 33.34 y (SD ± 7.33 y)) was taken for comparison. Results: The results showed that, following acupuncture treatment, CIN and AN patients showed improvement (SD± mean) in their binocular BCVA (baseline: 0.45 ± 0.36; between: 0.53 ± 0.34 and post-treatment: 0.51 ± 0.28), and in their monocular contrast sensitivity (baseline: 11.29 ± 12.35; between: 11.43 ± 11.45 and post-treatment: 14.0 ± 12.22). The post-/baseline-difference showed a significant improvement in contrast vision and in BCVA for CIN and AN patients, but not for controls (p = 0.029 and p = 0.007, respectively). The effect of the eye showed also, within CIN and AN, significant values for the examined parameters in the post-/baseline difference (p = 0.004 and p ≤ 0.001). Evaluated only binocularly, the respective between-/baseline and post-/baseline difference in the CIN and AN group showed significant values (p < 0.045). Two AN patients reported reduction of oscillations. Among general subjective symptoms, our patients reported reduction of tiredness and headache attacks, improvement of vision, and shorter sleep onset time. Conclusion: The applied acupuncture protocol showed improvement in the visual function of nystagmus patients and thus, in their quality of life. Further studies are mandatory to differentiate which group of nystagmus patients would benefit more from acupuncture.
Influence of Growth Velocity on the Separation of Primary Silicon in Solidified Al-Si Hypereutectic Alloy Driven by a Pulsed Electric Current
Authors: Zhang Yunhu , Ye Chunyang , Xu Yanyi , Zhong Honggang , Chen Xiangru , Miao Xincheng , Song Changjiang , Zhai Qijie
Published: May 2017

Investigating the separation of the primary silicon phase in Al-Si hypereutectic alloys is of high importance for the production of solar grade silicon. The present paper focuses on the effect of growth velocity on the electric current pulse (ECP)-induced separation of primary silicon in a directionally solidified Al-20.5 wt % Si hypereutectic alloy. Experimental results show that lower growth velocity promotes the enrichment tendency of primary silicon at the bottom region of the sample. The maximum measured area percentage of segregated primary silicon in the sample solidified at the growth velocity of 4 μm/s is as high as 82.6%, whereas the corresponding value is only 59% in the sample solidified at the growth velocity of 24 μm/s. This is attributed to the fact that the stronger forced flow is generated to promote the precipitation of primary silicon accompanied by a higher concentration of electric current in the mushy zone under the application of a slower growth velocity.
Fabrication of Cell-Laden Hydrogel Fibers with Controllable Diameters
Authors: Cheng Zhuoqun , Cui Maosheng , Shi Yu , Qin Yanding , Zhao Xin
Published: May 2017

Cell-laden hydrogel fibers are widely used as the fundamental building blocks to fabricate more complex functional three-dimensional (3D) structures that could mimic biological tissues. The control on the diameter of the hydrogel fibers is important so as to precisely construct structures in the above 3D bio-fabrication. In this paper, a pneumatic-actuated micro-extrusion system is developed to produce hydrogel fibers based on the crosslinking behavior of sodium alginate with calcium ions. Excellent uniformity has been obtained in the diameters of the fabricated hydrogel fibers as a proportional-integral-derivative (PID) control algorithm is applied on the driving pressure control. More importantly, a linear relationship has been obtained between the diameter of hydrogel fiber and the driving pressure. With the help of the identified linear model, we can precisely control the diameter of the hydrogel fiber via the control of the driving pressure. The differences between the measured and designed diameters are within ±2.5%. Finally, the influence of the calcium ions on the viability of the encapsulated cells is also investigated by immersing the cell-laden hydrogel fibers into the CaCl2 bath for different periods of time. LIVE/DEAD assays show that there is little difference among the cell viabilities in each sample. Therefore, the calcium ions utilized in the fabrication process have no impact on the cells encapsulated in the hydrogel fiber. Experimental results also show that the cell viability is 83 ± 2% for each sample after 24 h of culturing.
Geochemistry and Stable Isotopes of Travertine from Jordan Valley and Dead Sea Areas
Authors: Ibrahim Khalil , Makhlouf Issa , El Naqah Ali , Al-Thawabteh Sana’
Published: May 2017

Travertine deposits in Deir Alla, Suwayma, and Az Zara areas were investigated. Mineralogy, geochemistry, stable isotopes and age dating indicate the presence of low-Mg calcite, with minor quartz components. The variable isotope (δ13C and δ18O) signatures indicate dependence on water temperature and water/rock isotopic exchange. In contrast, the high δ13C values in some travertine samples reflect 12CO2 degassing processes, increased input of 13C-enriched groundwater, and the presence of surface and groundwater hydrological systems. The high δ18O values may be attributed to evaporation effects and low water temperature during the formation of localized travertine. The age of travertine is the Late Pleistocene.
Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products
Authors: Annamalai Murali , Hristeva Stanimira , Bielska Martyna , Ortega Raquel , Kumar Kamal
Published: May 2017

Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp3 character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp3 features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium.
Electrophilic Trifluoromethylselenolation of Boronic Acids
Authors: Ghiazza Clément , Tlili Anis , Billard Thierry
Published: May 2017

Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF3SeCl and use it in various reactions. Herein, we continue our study of the reactivity scope of this preformed reagent. Cross-coupling reactions with aromatic and heteroaromatic boronic acids have been investigated. The expected products have been obtained, using a stoichiometric amount of copper, with moderate yields.
Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome—A Concise Review
Authors: Hofer Michal , Hoferová Zuzana , Depeš Daniel , Falk Martin
Published: May 2017

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.
Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers
Authors: Liu Jian-Yong , Wang Chen , Zhu Chun-Hui , Zhang Zhi-Hong , Xue Jin-Ping
Published: May 2017

Two novel glucosylated zinc(ІІ) phthalocyanines 7a–7b, as well as the acetyl-protected counterparts 6a–6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a–7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC50 as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy.
Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles
Authors: Kókai Eszter , Halász Judit , Dancsó András , Nagy József , Simig Gyula , Volk Balázs
Published: May 2017

The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized.
Synthesis and Characterization of Constrained Geometry Oxygen and Sulphur Functionalized Cyclopentadienylchromium Complexes and Their Use in Catalysis for Olefin Polymerization
Authors: Zhao Ruiguo , Ma Jun , Zhang Hao , Huang Jiling
Published: May 2017

A series of constrained geometry O-functionalized cyclopentadienylchromium complexes (1–6) and a S-functionalized cyclopentadienylchromium complex (7) were first synthesized, characterized, and tested as catalyst precursors for the olefin polymerization. In the presence of MAO, the complexes exhibited high catalytic activity for the polymerization of ethylene. It is shown that ligand variations can have a substantial effect on catalyst activity and stability. The effect of Al/Cr ratio on catalytic activity was also studied.
Development of Optimized Inhibitor RNAs Allowing Multisite-Targeting of the HCV Genome
Authors: Romero-López Cristina , Lahlali Thomas , Berzal-Herranz Beatriz , Berzal-Herranz Alfredo
Published: May 2017

Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs. The catalytic domain was preserved while the aptamer RNA domain was evolved to contain two binding sites, one mapping to the highly conserved IIIf domain of the HCV genome’s internal ribosome entry site (IRES), and the other either to IRES domain IV (which contains the translation start codon) or the essential linker region between domains I and II. These chimeric molecules efficiently and specifically interfered with HCV IRES-dependent translation in vitro (with IC50 values in the low µM range). They also inhibited both viral translation and replication in cell culture. These findings highlight the feasibility of using in vitro selection strategies for obtaining improved RNA molecules with potential clinical applications.
Endophytic Bacteria Isolated from Panax ginseng Improves Ginsenoside Accumulation in Adventitious Ginseng Root Culture
Authors: Song Xiaolin , Wu Hao , Yin Zhenhao , Lian Meilan , Yin Chengri
Published: May 2017

Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious roots of ginseng than that in ginseng cultivated in the field. In this study, we investigated the effects of endophytic bacterial elicitors on biomass and ginsenoside production in adventitious roots cultures of Panax ginseng. Endophyte LB 5-3 as an elicitor could increase biomass and ginsenoside accumulation in ginseng adventitious root culture. After 6 days elicitation with a 10.0 mL of strain LB 5-3, the content of total ginsenoside was 2.026 mg g−1 which was four times more than that in unchallenged roots. The combination of methyl jasmonate and strain LB 5-3 had a negative effect on ginseng adventitious root growth and ginsenoside production. The genomic DNA of strain LB 5-3 was sequenced, and was found to be most closely related to Bacillus altitudinis (KX230132.1). The challenged ginseng adventitious root extracts exerted inhibitory effect against the HepG2 cells, which IC50 value was 0.94 mg mL−1.
14,15-Secopregnane-Type Glycosides with 5α:9α-Peroxy and Δ6,8(14)-diene Linkages from the Roots of Cynanchum stauntonii
Authors: Deng An-Jun , Yu Jin-Qian , Li Zhi-Hong , Ma Lin , Zhang Zhi-Hui , Qin Hai-Lin
Published: May 2017

Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA1, and UA2, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. The structures of the new compounds were characterized on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR and MS methods and chemical analysis. The isolation and identification of the new compounds graced the structural diversity of pregnane-type steroids from C. stauntonii.
Four Different Multimodal Setups for Non-Aerial Vehicle Simulations—A Case Study with a Speedboat Simulator
Authors: Casas Sergio , Fernández Marcos , Riera José
Published: May 2017

Vehicle simulators are multimodal interactive applications used in many human activities with different purposes. However, they are sometimes expensive systems that need to be carefully studied before they are designed and built, since some simulators can actually be much more expensive than the simulated vehicle. This is an important issue, although it is sometimes overlooked in scientific research. This paper proposes four different setups (with a variety of visual, sound, motion generation, and user-input interfaces) for non-aerial vehicle simulation, using a speedboat simulator as a case study. These setups are analysed in terms of their cost and their effectiveness is discussed. Rough figures are provided to give a comparative insight into the economic order of magnitude necessary to design and build a vehicle simulator.
Vegetable and Fruit Intake and Fracture-Related Hospitalisations: A Prospective Study of Older Women
Authors: Blekkenhorst Lauren , Hodgson Jonathan , Lewis Joshua , Devine Amanda , Woodman Richard , Lim Wai , Wong Germaine , Zhu Kun , Bondonno Catherine , Ward Natalie , Prince Richard
Published: May 2017

The importance of vegetable and fruit intakes for the prevention of fracture in older women is not well understood. Few studies have explored vegetable and fruit intakes separately, or the associations of specific types of vegetables and fruits with fracture hospitalisations. The objective of this study was to examine the associations of vegetable and fruit intakes, separately, and specific types of vegetables and fruits with fracture-related hospitalisations in a prospective cohort of women aged ≥70 years. Vegetable and fruit intakes were assessed at baseline (1998) in 1468 women using a food frequency questionnaire. The incidence of fracture-related hospitalisations over 14.5 years of follow-up was determined using the Hospital Morbidity Data Collection, linked via the Western Australian Data Linkage System. Fractures were identified in 415 (28.3%) women, of which 158 (10.8%) were hip fractures. Higher intakes of vegetables, but not fruits, were associated with lower fracture incidence. In multivariable-adjusted models for vegetable types, cruciferous and allium vegetables were inversely associated with all fractures, with a hazard ratio (HR) (95% confidence interval) of 0.72 (0.54, 0.95) and 0.66 (0.49, 0.88), respectively, for the highest vs. lowest quartiles. Increasing vegetable intake, with an emphasis on cruciferous and allium vegetables, may prevent fractures in older postmenopausal women.
Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes
Authors: Mattera Rosanna , Benvenuto Monica , Giganti Maria , Tresoldi Ilaria , Pluchinotta Francesca , Bergante Sonia , Tettamanti Guido , Masuelli Laura , Manzari Vittorio , Modesti Andrea , Bei Roberto
Published: May 2017

Cardiovascular diseases are the main cause of mortality and morbidity in the world. Hypertension, ischemia/reperfusion, diabetes and anti-cancer drugs contribute to heart failure through oxidative and nitrosative stresses which cause cardiomyocytes nuclear and mitochondrial DNA damage, denaturation of intracellular proteins, lipid peroxidation and inflammation. Oxidative or nitrosative stress-mediated injury lead to cardiomyocytes apoptosis or necrosis. The reactive oxygen (ROS) and nitrogen species (RNS) concentration is dependent on their production and on the expression and activity of anti-oxidant enzymes. Polyphenols are a large group of natural compounds ubiquitously expressed in plants, and epidemiological studies have shown associations between a diet rich in polyphenols and the prevention of various ROS-mediated human diseases. Polyphenols reduce cardiomyocytes damage, necrosis, apoptosis, infarct size and improve cardiac function by decreasing oxidative stress-induced production of ROS or RNS. These effects are achieved by the ability of polyphenols to modulate the expression and activity of anti-oxidant enzymes and several signaling pathways involved in cells survival. This report reviews current knowledge on the potential anti-oxidative effects of polyphenols to control the cardiotoxicity induced by ROS and RNS stress.