bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of anthocyanins on the prevention and treatment of cancer
Authors: Lin Bo‐Wen , Gong Cheng‐Chen , Song Hai‐Fei , Cui Ying‐Yu 
Published: September 2016

Anthocyanins are a class of water‐soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti‐inflammation; anti‐mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti‐invasion; anti‐metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy. In this review, the latest progress on the anticancer activities of anthocyanins and the underlying molecular mechanisms is summarized using data from basic research in vitro and in vivo, from clinical trials and taking into account theory and practice.Linked ArticlesThis article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
In silico prediction of chemical mechanism of action via an improved network‐based inference method
Authors: Wu Zengrui , Lu Weiqiang , Wu Dang , Luo Anqi , Bian Hanping , Li Jie , Li Weihua , Liu Guixia , Huang Jin , Cheng Feixiong , Tang Yun 
Published: September 2016

Background and PurposeDeciphering chemical mechanism of action (MoA) enables the development of novel therapeutics (e.g. drug repositioning) and evaluation of drug side effects. Development of novel computational methods for chemical MoA assessment under a systems pharmacology framework would accelerate drug discovery and development with greater efficiency and low cost.Experimental ApproachIn this study, we proposed an improved network‐based inference method, balanced substructure‐drug‐target network‐based inference (bSDTNBI), to predict MoA for old drugs, clinically failed drugs and new chemical entities. Specifically, three parameters were introduced into network‐based resource diffusion processes to adjust the initial resource allocation of different node types, the weighted values of different edge types and the influence of hub nodes. The performance of the method was systematically validated by benchmark datasets and bioassays.Key ResultsHigh performance was yielded for bSDTNBI in both 10‐fold and leave‐one‐out cross validations. A global drug‐target network was built to explore MoA of anticancer drugs and repurpose old drugs for 15 cancer types/subtypes. In a case study, 27 predicted candidates among 56 commercially available compounds were experimentally validated to have binding affinities on oestrogen receptor α with IC50 or EC50 values ≤10 μM. Furthermore, two dual ligands with both agonistic and antagonistic activities ≤1 μM would provide potential lead compounds for the development of novel targeted therapy in breast cancer or osteoporosis.Conclusion and ImplicationsIn summary, bSDTNBI would provide a powerful tool for the MoA assessment on both old drugs and novel compounds in drug discovery and development.
Proanthocyanidins and hydrolysable tannins: occurrence, dietary intake and pharmacological effects
Authors: Smeriglio Antonella , Barreca Davide , Bellocco Ersilia , Trombetta Domenico 
Published: September 2016

Tannins are a heterogeneous group of high MW, water‐soluble, polyphenolic compounds, naturally present in cereals, leguminous seeds and, predominantly, in many fruits and vegetables, where they provide protection against a wide range of biotic and abiotic stressors. Tannins exert several pharmacological effects, including antioxidant and free radical scavenging activity as well as antimicrobial, anti‐cancer, anti‐nutritional and cardio‐protective properties. They also seem to exert beneficial effects on metabolic disorders and prevent the onset of several oxidative stress‐related diseases. Although the bioavailability and pharmacokinetic data for these phytochemicals are still sparse, gut absorption of these compounds seems to be inversely correlated with the degree of polymerization. Further studies are mandatory to better clarify how these molecules and their metabolites are able to cross the intestinal barrier in order to exert their biological properties. This review summarizes the current literature on tannins, focusing on the main, recently proposed mechanisms of action that underlie their pharmacological and disease‐prevention properties, as well as their bioavailability, safety and toxicology.Linked ArticlesThis article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Pharmaceutically inhibiting polo‐like kinase 1 exerts a broad anti‐tumour activity in retinoblastoma cell lines
Authors: Schwermer Melanie , Dreesmann Sabine , Eggert Angelika , Althoff Kristina , Steenpass Laura , Schramm Alexander , Schulte Johannes H , Temming Petra 
Published: September 2016

AbstractBackgroundRetinoblastoma is the most common malignant cancer of the eye in children. Although metastatic retinoblastoma is rare, cure rates for this advanced disease remain below 50%. High‐level polo‐like kinase 1 expression in retinoblastomas has previously been shown to be correlated with adverse outcome parameters. Polo‐like kinase 1 is a serine/threonine kinase involved in cell cycle regulation at the G2/M transition. Polo‐like kinase 1 inhibition has been demonstrated to have anti‐tumour effects in preclinical models of several paediatric tumours. Here, we assessed its efficacy against retinoblastoma cell lines.MethodsExpression of polo‐like kinase 1 was determined in a panel of retinoblastoma cell lines by polymerase chain reaction and western blot analysis. We analysed viability (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) (MTT assay), proliferation (5‐bromo‐2'‐deoxyuridine enzyme‐linked immunosorbent assay), cell cycle progression (propidium iodid staining) and apoptosis (cell death enzyme‐linked immunosorbent assay) in three retinoblastoma cell lines after treatment with two adenosine triphosphate‐competitive polo‐like kinase 1 inhibitors, BI6727 or GSK461364. Activation of polo‐like kinase 1 downstream signalling components including TP53 were assessed.ResultsTreatment of retinoblastoma cells with either BI6727 or GSK461364 reduced cell viability and proliferative capacity and induced both cell cycle arrest and apoptosis. Polo‐like kinase 1 inhibition also induced the p53 signalling pathway. Analysis of key players in cell cycle control revealed that low nanomolar concentrations of either polo‐like kinase 1 inhibitor upregulated cyclin B1 and increased activated cyclin‐dependent kinase 1 (phosphorylated at Y15) in retinoblastoma cell lines.ConclusionsThese preclinical data indicate that polo‐like kinase 1 inhibitors could be useful as components in rationally designed chemotherapy protocols to treat patients with metastasized retinoblastoma in early phase clinical trials.
Miller‐Dieker Syndrome with unbalanced translocation 45, X, psu dic(17;Y)(p13;p11.32) detected by fluorescence in situ hybridization and G‐banding analysis using high resolution banding technique
Authors: Mishima Takashi , Watari Michiko , Iwaki Yutaka , Nagai Takumi , Kawamata‐Nakamura Miho , Kobayashi Yukako , Fujieda Satoko , Oikawa Mamoru , Takahashi Nobuhiro , Keira Mitsuaki , Yoshida Hiroshi , Tonoki Hidefumi 
Published: September 2016

AbstractLissencephaly is one of the central nervous system anomalies of Miller‐Dieker Syndrome (MDS). Fetuses with lissencephaly have an abnormal smooth brain with fewer folds and grooves that will be detected by ultrasounds or fetal magnetic resonance imaging (MRI) after 30 weeks of gestation. We report a fetus with lissencephaly diagnosed as Miller‐Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1‐,RARA+, SRY+, DYZ3+) by G‐banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome.
Group Modeling: A Unified Velocity‐Based Approach
Authors: Ren Z. , Charalambous P. , Bruneau J. , Peng Q. , Pettré J. 
Published: September 2016

AbstractCrowd simulators are commonly used to populate movie or game scenes in the entertainment industry. Even though it is crucial to consider the presence of groups for the believability of a virtual crowd, most crowd simulations only take into account individual characters or a limited set of group behaviors. We introduce a unified solution that allows for simulations of crowds that have diverse group properties such as social groups, marches, tourists and guides, etc. We extend the Velocity Obstacle approach for agent‐based crowd simulations by introducing Velocity Connection; the set of velocities that keep agents moving together while avoiding collisions and achieving goals. We demonstrate our approach to be robust, controllable, and able to cover a large set of group behaviors.
Developing and assessing a cadaveric training model for transanal total mesorectal excision: initial experience in the UK and USA
Authors: Penna M. , Whiteford M. , Hompes R. , Sylla P. 
Published: September 2016

AbstractAimTransanal total mesorectal excision (taTME) has become one of the most promising technical advancements in the surgical treatment of rectal cancer, with rising numbers of surgeons seeking training. We describe our experience with human cadaveric courses for taTME delivered in two countries.MethodFour fresh human cadaveric workshops conducted in Oxford, UK, in 2015 and two in Chicago, USA, in 2013−2014, trained a total of 52 surgeons. Parameters of operative performance for each delegate were recorded. Previous surgical experience and uptake of taTME in the surgeons’ clinical setting were surveyed.ResultsForty‐seven taTME cases were performed on cadaveric models. Participating surgeons had previous experience in laparoscopic TME surgery and transanal approaches but limited taTME exposure. The purse‐string remained occluded throughout in 93% of UK and 60% of US cases. Operative timings for key procedural steps were similar between the two countries with a mean time from start of circumferential dissection to peritoneal entry of 79.5 min (range 25–155). 96% of surgeons dissected transanally to a level S2 or above. The TME specimen quality was complete or near complete in 81%, with improvements noted between the first and second procedure performed. 81% of surgeons surveyed are currently performing taTME in their local hospitals.ConclusionFresh‐frozen cadavers provide excellent teaching models for complex pelvic surgery. A structured training curriculum including reading material, dry‐lab purse‐string practice and postcourse mentorship will provide surgeons with a more complete training package and ongoing support, to ultimately ensure the safe introduction of taTME in the clinical setting.
PCL‐PEG‐PCL film promotes cartilage regeneration in vivo
Authors: Fu Na , Liao Jinfeng , Lin Shiyu , Sun Ke , Tian Taoran , Zhu Bofeng , Lin Yunfeng 
Published: September 2016

AbstractObjectiveManagement of chondral defects has long been a challenge due to poor self‐healing capacity of articular cartilage. Many approaches, ranging from symptomatic treatment to structural cartilage regeneration, have obtained very limited satisfactory results. Cartilage tissue engineering, which involves optimized combination of novel scaffolds, cell sources and growth factors, has emerged as a promising strategy for cartilage regeneration and repair. In this study, the aim was to investigate the role of poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL, PCEC) PCEC scaffold in cartilage repair.Materials and methodsFirst, PCEC film was fabricated, and its characteristics were tested using SEM and AFM. Cell (rASC – rat adipose‐derived stem cells, and mASCs – green fluorescent mouse adipose‐derived stem cells) morphologies on PCEC film were observed using SEM and fluorescence microscopy, after cell seeding. Tests of cell viability on PCEC film were conducted using the CCK‐8 assay. Furthermore, full cartilage defects in rats were created, and PCEC films were implanted, to evaluate their healing effects, over 8 weeks.ResultsIt was found that PCEC film, as a biomaterial implant, possessed good in vitro properties for cell adhesion, migration and proliferation. Importantly, in the in vivo experiment, PCEC film exhibited desirable healing outcomes.ConclusionsThese results demonstrated that PCEC film was a good scaffold for cartilage tissue engineering for improving cell proliferation and adhesion and could lead to excellent repair of cartilage defects.
Low vitamin D levels are not a contributing factor to higher prevalence of depressive symptoms in people with Type 2 diabetes mellitus: the Hoorn study
Authors: Westra S. , Simsek S. , Rutters F. , Krul‐Poel Y. M. H. , Stehouwer C. D. A. , Dekker J. M. , Pouwer F. 
Published: September 2016

AbstractAimTo test whether a low serum 25‐hydroxyvitamin D level explains the greater prevalence of depression among people with Type 2 diabetes.MethodsWe performed a cross‐sectional analysis of 527 people, aged 60–87 years, who participated in a population‐based cohort study. Type 2 diabetes, impaired glucose tolerance, impaired fasting glucose and normal glucose tolerance were defined according to the 2006 WHO criteria. The Centre for Epidemiologic Studies Depression questionnaire was administered, using a cut‐off score of ≥ 16 to determine clinically relevant depressive symptoms.ResultsLogistic regression analysis confirmed that women with impaired glucose tolerance/impaired fasting glucose and people with Type 2 diabetes did have a higher risk of depressive symptoms [unadjusted odds ratios 3.66 (95% CI 1.59 to 8.43) and 3.04 (95% CI 1.57 to 5.88), respectively], compared with people with normal glucose tolerance. Serum 25‐hydroxyvitamin D level was not a mediating factor in the association between impaired glucose tolerance/impaired fasting glucose or Type 2 diabetes and depressive symptoms [unstandardized indirect effect 0.001 (95% CI −0.063 to 0.079) and 0.004 (95% CI −0.025 to 0.094), respectively].ConclusionsThe study found no evidence that low vitamin D levels are a contributing factor to higher depression scores in people with Type 2 diabetes.
Risk of future microvascular and macrovascular disease in people with Type 1 diabetes of very long duration: a national study with 10‐year follow‐up
Authors: Adamsson Eryd S. , Svensson A.‐M. , Franzén S. , Eliasson B. , Nilsson P. M. , Gudbjörnsdottir S. 
Published: September 2016

AbstractAimsTo describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications.MethodsWe included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10‐year follow‐up period was studied in all individuals who had no complications at baseline.ResultsAmong people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid‐lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow‐up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration.ConclusionsPeople with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
Ventrolateral periaqueductal grey matter neurotransmission modulates cardiac baroreflex activity
Authors: Lagatta Davi C. , Ferreira‐Junior Nilson C. , Deolindo Milena , Corrêa Fernando M. A. , Resstel Leonardo B. M. 
Published: September 2016

AbstractBaroreflex activity is a neural mechanism responsible for short‐term adjustments in blood pressure (BP). Several supramedullary areas, which send projections to the medulla, are able to control this reflex. In this context, the ventrolateral part of the periaqueductal grey matter (vlPAG), which is a mesencephalic structure, has been suggested to regulate the cardiovascular system. However, its involvement in baroreflex control has never been addressed. Therefore, our hypothesis is that the vlPAG neurotransmission is involved in baroreflex cardiac activity. Male Wistar rats had stainless steel guide cannulae unilaterally or bilaterally implanted in the vlPAG. Afterward, a catheter was inserted into the femoral artery for BP and HR recording. A second catheter was implanted into the femoral vein for baroreflex activation. When the nonselective synaptic blocker cobalt chloride (CoCl2) was unilaterally injected into the vlPAG, in either the left or the right hemisphere, it increased the tachycardic response to baroreflex activation. However, when CoCl2 was bilaterally microinjected into the vlPAG it decreased the tachycardic response to baroreflex stimulation. This work shows that vlPAG neurotransmission is involved in modulation of the tachycardic response of the baroreflex. Moreover, we suggest that the interconnections between the vlPAG of both hemispheres are activated during baroreflex stimulation. In this way, our work helps to improve the understanding about brain–heart circuitry control, emphasizing the role of the autonomic nervous system in such modulation.
Arbuscular mycorrhizal fungal‐assisted phytoremediation of soil contaminated with persistent organic pollutants: a review
Authors: Lenoir I. , Lounes‐Hadj Sahraoui A. , Fontaine J. 
Published: September 2016

Concern about soil contamination by persistent organic pollutants (POPs) that originate from intensive anthropogenic activities has now become a priority in industrialized countries. Some of these compounds can accumulate in the environment and threaten the development of living organisms because of their acute toxicity, mutagenicity and carcinogeneity. Among remediation methods for polluted soil, arbuscular mycorrhizal fungi (AMF)‐assisted phytoremediation is an attractive approach to plant‐based environmental remediation. Arbuscular mycorrhizal associations are important in the restoration of degraded ecosystems because of the benefits to their symbiotic partners. Arbuscular mycorrhizal fungi are not only able to facilitate plant establishment and survival inPOP‐contaminated soil by protecting plants against the phytotoxicity ofPOPs, but also enhance soil bioremediation by stimulating telluric microbial activity and by improving soil structure. This phytotechnology, however, is still in its infancy and there has been little research on aged‐contaminated soils. Itsin situeffectiveness remains to be proved. This review summarizes current knowledge about the effect ofPOPson the establishment and functioning of arbuscular mycorrhizal symbiosis and its contribution to the phytoremediation ofPOP‐polluted soil. It focuses on recent developments that aim to improve the efficiency ofAMF‐assisted phytoremediation in the dissipation ofPOPsand future directions.HighlightsArbuscular mycorrhizal fungi (AMF) provide a means of plant‐based environmental clean‐up.AMF‐assisted phytoremediation is based on the synergistic actions of plants and telluric microorganisms.Research is in progress to improve efficiency of this phytotechnology and management of the biomass produced.Development of integrated approaches that combine land remediation with biomass conversion processes is required.
Accurate measurement of resistant soil organic matter and its stoichiometry
Authors: Kirkby C. A. , Richardson A. E. , Wade L. J. , Batten G. D. , Blanchard C. L. , Mclaren G. , Zwart A. B. , Kirkegaard J. A. 
Published: September 2016

Research suggests that relatively stable, fine fraction soil organic matter (FF‐SOM) has almost constant concentrations of nitrogen, phosphorus and sulphur (NPS) per unit of carbon (C), although there are considerable differences in the datasets used. Such differences could, in agricultural situations in particular (where inorganic nutrients are often added), result from substantial concentrations of inorganic‐N, inorganic‐Pand inorganic‐Sthat remain in the soil. We assessed the efficacy of removal of inorganic nutrients with different washing procedures (0.1 or 0.5 mhydrochloric acid solution). Even after repeated additions of inorganic‐N, inorganic‐Sand inorganic‐Pto soil as part of a long‐term incubation experiment, washing soil with 0.1 mHClwas effective at removing residual inorganic‐Nand inorganic‐S, but not effective at removing inorganic‐P. We demonstrate that estimates ofC:N,C:SandC:Pratios inFF‐SOMcan be substantially underestimated when these washing procedures are not carried out as part of the soil analyses. This leads to overestimation of the amounts ofN,PandSthat are required for co‐sequestration ofCduring the formation ofFF‐SOM. BecausePis essential for the formation ofFF‐SOM, more research is needed to obtain an accurate measure of thePrequired per unit ofFF‐SOM. Although washing with 0.1 mHClalso removed someFF‐C, we suggest a method to compensate for this. We tested the procedure on soil with clay contents ranging from 8 to 60%; however, the stronger acid might be more suitable for soil with larger clay contents.HighlightsWhat is the best method to measure the size and stoichiometry of the stable soil organic matter pool?Enlarging this soil organic matter pool could help restore fertility and mitigate climate change.Washing soil with dilute acid can remove excess inorganic nutrients, but it also removes organic carbon.We recommend the size of the pool on unwashed soil and the stoichiometry on washed soil is measured.