bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethanol: A Promising Green Solvent for the Deconstruction of Lignocellulose
Authors: Tekin Kubilay , Hao Naijia , Karagoz Selhan , Ragauskas Arthur J. 
Published: August 2018

AbstractGrowing energy demand, environmental impact, energy security issues, and rural economic development have encouraged the development of sustainable renewable fuels. Nonfood lignocellulosic biomass is a suitable source for sustainable energy because the biomass feedstocks are low cost, abundant, and carbon neutral. Recent thermochemical conversion studies are frequently directed at converting biomass into high‐quality liquid fuel precursors or chemicals in a single step. Supercritical ethanol has been selected as a promising solvent medium to deconstruct lignocellulosic biomass because ethanol has extraordinary solubility towards lignocellulosic biomass and can be resourced from cellulosic ethanol facilities. This review provides a critical insight into both catalytic and noncatalytic strategies of lignocellulose deconstruction. In this context, the supercritical ethanol deconstruction pathways are thoroughly reviewed; GC‐MS, 1D and 2D NMR spectroscopy, and elemental analysis strategies towards liquid biomass deconstruction products are also critically presented. This review aims to provide readers a broad and accurate roadmap of novel biomass to biofuel conversion techniques.
Fañanas cells—the forgotten cerebellar glia cell type: Immunocytochemistry reveals two potassium channel‐related polypeptides, Kv2.2 and Calsenilin (KChIP3) as potential marker proteins
Authors: Goertzen Angelika , Veh Rüdiger W. 
Published: August 2018

AbstractFor long times astrocytes had been regarded as supporting cells, passively filling the spaces between neuronal cell bodies and their extensions. Now it is known that astrocytes are actively involved in a variety of important biological functions such as regulating cerebral blood flow, supporting neuronal metabolism, controlling the extracellular potassium concentration, and clearing neurotransmitters from the extracellular space. In line with this multitude of tasks astrocytes display conspicuous functional and regional heterogeneity. Using three complementary labeling methods nine classes of astrocytes have been differentiated, which were termed protoplasmic, fibrous, velate, radial, and perivascular astrocytes in addition to Bergmann, marginal, and ependymal glial cells. To complete this list retinal Müller cells and a largely forgotten astrocytic cell type, the “feathered cell” of Fañanas need to be added. So far, Fañanas cells could be only recognized with the tedious gold‐sublimate procedure. Consequently, data indicating a potential biological function are completely missing. In a parallel investigation we used a battery of antibodies against potassium channels and related proteins to identify potential marker proteins for the immunocytochemical visualization of distinct cell types in the cerebellar cortex. Here we present novel marker proteins, the Kv2.2 potassium channel and calsenilin, to visualize Fañanas cells in the cerebellar Purkinje cell layer. Such markers will allow to identify Fañanas cell subsequent to patching and electrophysiological characterization. This may pave the path to obtain new functional data, which may be helpful to understand the role of these enigmatic cells in normal biological function and disease.
The effect of the inflammatory species hypochlorous acid on the corrosion and surface damage of Ti‐6Al‐4V and CoCrMo alloys
Authors: Kubacki Gregory W. , Gilbert Jeremy L. 
Published: August 2018

AbstractPerformance of metallic orthopedic alloys is dependent on the local biological conditions within the joint. Inflammation within a joint can lead to severe conditions at the surface of the implant and may represent a driving force of corrosion which is not well understood. In this study, the corrosion response of CoCrMo and Ti‐6Al‐4V alloys was studied in hypochlorous acid (HOCl) saline solutions, which served as a simulated inflammatory environment. Anodic polarization and electrochemical impedance spectroscopy were used to evaluate the electrochemical behavior of these alloys in a range of hypochlorous acid solutions. The open circuit potential of CoCrMo rose to over 600 mV (vs. Ag/AgCl) in 30 mM HOCl solutions while the corresponding corrosion current increased three orders of magnitude over controls. Visual analysis of CoCrMo disks after immersion in 50 mM HOCl for 5 days revealed extensive surface damage. This study shows that HOCl can polarize CoCrMo surfaces above the transpassive potential without an external power source. Ultimately, long‐term exposure to HOCl within an inflamed joint may significantly affect patient outcomes through accelerated generation of corrosion products. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3185–3194, 2018.
Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells
Authors: Li Quanying , Tang Hongna , Hu Fangfang , Qin Changjiang 
Published: August 2018

AbstractHypoxia induces epithelial‐mesenchymal transition (EMT) in tumorigenesis. A‐kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia‐inducible factor‐1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia‐induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β‐catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia‐induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β‐catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.
Curcumin‐mediated demethylation of the proximal promoter CpG island enhances the KLF4 recruitment that leads to increased expression of p21Cip1 in vitro
Authors: Chatterjee Biji , Ghosh Krishna , Kanade Santosh R. 
Published: August 2018

AbstractCurcumin, the active component of the spice turmeric, induce global DNA hypomethylation as it has been shown to inhibit DNA methyltransferases. It promotes cell death in cancer cells by arresting in the G1 phase. It was explained to cause increased expression of cell cycle regulator, p21 (WAF1/Cip1); however, the mechanism remains not clear. The p21 promoter harvests a CpG island (CGI) in the proximal region enriched with CG dinucleotide clusters with Kruppel‐like factor 4 (KLF4) transcription factor binding site. We probed the p21 promoter CGI (spanning from −135 to +12, respective to the transcription start site) to detect alterations in cytosine methylation level in response to curcumin exposure in four different human cancer cell lines: A431, A549, MCF7, and HeLa. We observed curcumin (20 µM) treatment significantly increased the expression of p21, and the promoter CGI was demethylated in a dose‐dependent manner. The curcumin significantly raised the level KLF4 and enhanced the p21 promoter occupancy by KLF4. From our results we hypothesize that curcumin‐mediated demethylation of the p21 proximal promoter and increased KLF4 expression as well as its binding to its proximal promoter could serve as a mechanism that could be hypothesized to cause upregulation of p21 in presence of curcumin and thus its therapeutic implications could further be investigated.
Effects of mycoplasma infection on the host organism response via p53/NF‐κB signaling
Authors: Borchsenius Sergey N. , Daks Alexandra , Fedorova Olga , Chernova Olga , Barlev Nickolai A. 
Published: August 2018

AbstractMycoplasmas are bacteria lacking the cell wall, which is the major characteristic of this taxonomic class (Mollicutes). Among bacteria, mycoplasmas possess the smallest genome known for free‐living organisms. This feature limits the autonomy of bacteria and makes them increasingly susceptible to changes in the host organism. Many mycoplasmas themselves cause pathological changes in the host organism, often complicated by immune disorders. Infection with certain strains of mycoplasma results in the activation of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells, which is the major mediator of the inflammatory response. Furthermore, mycoplasmas can inhibit p53‐mediated checkpoint control of cell cycle and apoptosis. Collectively, these properties indicate that mycoplasmas might act as cancer‐promoting factors. In this review, we summarize the information known to date on the role of mycoplasmas in the regulation of the host immune response and their functional interactions with p53.
Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP
Authors: Gao Jian , Rong Yingxue , Huang Yuxing , Shi Peng , Wang Xitao , Meng Xuan , Dong Jiahong , Wu Congying 
Published: August 2018

AbstractA majority of hepatocellular carcinomas (HCCs) combine with liver cirrhosis. The cirrhotic liver has been implicated in interfering with the effects of HCC‐targeted drugs, including sorafenib. Alterations in the tumor microenvironment of the cirrhotic liver include both biochemical and biomechanical factors. In this study, we induced sorafenib resistance in HCC cells. We observed changes in cell morphology, cytoskeletal architecture, and cellular stiffness in these sorafenib‐resistant cells, resembling those adapted to stiffer substrates. To examine the contribution of mechanical factors in HCC cell growth and drug resistance, we used an in vitro cell culture system with adjustable stiffness mimicking the normal or cirrhotic liver tissues. We identified that mechanical adaptation conferred HCC cells with increased motility and sorafenib resistance. We further reported the mechanism underlying the involvement of the transcription coactivator YAP. Our results underline the important role of mechanical factors in the interaction between tumor cells and their microenvironment.
Activation of type 4 metabotropic glutamate receptor promotes cell apoptosis and inhibits proliferation in bladder cancer
Authors: Zhang Zhichao , Liu Yingfei , Wang Ke , Zhu Kun , Zheng Xiaoyan , Wang Li , Luan Yan , Wang Xinyang , Lu Haixia , Wu Kaijie , Chen Xinlin , He Dalin , Liu Yong 
Published: August 2018

AbstractBladder cancer, the second most common genitourinary malignancy, severely endangers the human health. Rising evidence suggests that metabotropic glutamate receptors (mGluRs) are involve in tumor progression. In this study, we observed that metabotropic glutamate receptor 4 (mGluR4) was functionally expressed in normal and cancerous bladder cells and its expression was positively correlated with high bladder cancer grading. We further confirmed that the activation of mGluR4 by VU0155041, an mGluR4‐specific agonist, decreased cyclic adenosine monophosphate (cAMP) concentration and cell viability, promoted apoptosis and inhibited proliferation in bladder cancer cells, whereas MSOP (group III mGluR antagonist) or mGluR4 knockdown eliminated the effects of mGluR4 activity. Western blotting revealed the decreased cyclin D1 expression, increased procaspase‐8/9/3 cleavage, and unbalanced Bcl‐2/Bax expression in bladder cancer cell lines after mGluR4 activation, and likewise MSOP and mGluR4 knockdown abrogated the actions of mGluR4 activity. In vivo study showed that mGluR4 activation significantly inhibited tumor growth of bladder cancer via suppressing proliferation and promoting apoptosis. Furthermore, upregulation of phosphatase and tensin homolog (PTEN) and inhibition of Akt phosphorylation were also observed after mGluR4 activation. Similar with VU0155041, the Akt‐specific inhibitor markedly promoted apoptosis and inhibited proliferation. Nevertheless, the PTEN‐specific inhibitor significantly abolished the mGluR4 activation‐induced cell apoptosis and proliferative inhibition in bladder cancer cell lines. These results indicate that mGluR4 can regulate the switch between survival and death via the cAMP/PTEN/AKT signaling pathway in bladder cancer cells. Our findings suggest that mGluR4 has diagnostic and prognostic potential for bladder cancer, and the development of mGluR4 agonist may be a promising strategy for bladder cancer treatment.
Efficacy of different antidiabetic drugs based on metformin in the treatment of type 2 diabetes mellitus: A network meta‐analysis involving eight eligible randomized‐controlled trials
Authors: Peng Yan , Chen Shu‐Hong , Liu Xiao‐Nan , Sun Qing‐Yun 
Published: August 2018

AbstractDiabetes mellitus is one of the most prevalent metabolic diseases globally and it is increasing in prevalence. It is one of the most expensive diseases with respect to total health care costs per patient as a result of its chronic nature and its severe complications. To provide a more effective treatment of type 2 diabetes mellitus (T2DM), this study aims to compare different efficacies of six kinds of hypoglycemic drugs based on metformin, including glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin, in T2DM by a network meta‐analysis that were verified by randomized‐controlled trials (RCTs). Eight eligible RCT in consistency with the aforementioned six hypoglycemic drugs for T2DM were included. The results of network meta‐analysis demonstrated that the exenatide + metformin and vildagliptin + metformin regimens presented with better efficacy. Patients with T2DM with unsatisfactory blood glucose control based on diet control, proper exercise, and metformin treatment were included. The original regimen and dose of medication were unchanged, followed by the addition of glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin. The results of RCTs showed that all these six kinds of drugs reduced the HbA1c level. Compared with other regimens, exenatide + metformin reduced fasting plasma glucose (FPG), fasting plasma insulin (FPI), total cholesterol (TC), and homeostasis model assessment insulin resistance index (HOMA‐IR) levels, but increased the high‐density lipoprotein (HDL) level; vildagliptin + metformin decreased FPI and low‐density lipoprotein (LDL) levels; glibenclamide + metformin decreased the FPG level, but promoted HDL; and glimepiride + metformin decreased the TC level and rosiglitazone + metformin reduced the LDL level. Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.
In vitro evaluation of effects of metformin on morphine and methadone tolerance through mammalian target of rapamycin signaling pathway
Authors: Shirooie Samira , Sahebgharani Mousa , Esmaeili Jamileh , Dehpour Ahmad Reza 
Published: August 2018

AbstractThe chronic use of opioids leads to tolerance, psychological, and physical dependence that limits their use as an effective long‐term pain control. Several studies have shown that mammalian target of rapamycin (mTOR) plays a crucial role in the development of opioid tolerance. Metformin activates 5′ adenosine monophosphate‐activated protein kinase (AMPK) which directly suppresses the mTOR complex 1 signaling pathway. On the other hand, metformin can also inhibit mTOR directly and in an AMPK‐independent manner. Thus, in the current study, we aimed to investigate the effects of metformin on the development of morphine and/or methadone‐induced tolerance in human glioblastoma (T98G) cell line. We examined the effects of chronic treatment of morphine and/or methadone in the presence or absence of metformin with or without AMPK inhibitor (dorsomorphin hydrochloride) on levels of nitric oxide and cyclic adenosine monophosphate (cAMP), phosphorylated and dephosphorylated ribosomal protein S6 kinase β‐1 (S6K1) and 4E‐binding protein 1 (4E‐BP1) in T98G cells. Pretreatment of cells with metformin (40 µM) with or without AMPK inhibitor (dorsomorphin hydrochloride; 1 µM) before adding of morphine (2.5 µM) or methadone (1 µM) revealed a protective effects on the development of opioid tolerance. Prior administration of metformin reversed the elevation of nitric oxide levels induced by morphine (p < 0.001) and methadone (p < 0.001) and also prevented the raise of cAMP levels induced by morphine in T98G cells (p < 0.05). Contribution of mTOR signaling pathway in metformin‐induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E‐BP1, the downstream targets of mTOR. mTOR activation suppresses opioid‐induced antinociception, and its activity has also been increased during opioid tolerance.
Circular RNA circ‐VANGL1 as a competing endogenous RNA contributes to bladder cancer progression by regulating miR‐605‐3p/VANGL1 pathway
Authors: Zeng Zhihua , Zhou Wanming , Duan Lingxing , Zhang Jian , Lu Xiongbing , Jin Liang , Yu Yi 
Published: August 2018

AbstractIncreasing reports indicate that circular RNAs (circRNAs) are very important regulators in human diseases, including cancers. In bladder cancer (BC), several circRNAs have been reported to be involved in tumor progressions, such as circ‐ITCH and circTCF25. However, the functions of most circRNAs in BC still remains largely unknown. In this study, we identified a novel circRNA termed as circ‐VANGL1 by bioinformatics analysis. We found that circ‐VANGL1 was highly expressed in BC tissues compared with adjacent normal tissues. Furthermore, we showed that circ‐VANGL1 could serve as a prognostic marker for patients with BC. Through functional experiments, we found that circ‐VANGL1 knockdown significantly suppressed BC cell proliferation, cell cycle, migration, and invasion in vitro. Besides, circ‐VANGL1 silence inhibited BC cell propagation in vivo. Mechanistically, we identified circ‐VANGL1 as a sponge of miR‐605‐3p which targeted VANGL1 in BC cells. Through repressing miR‐605‐3p availability, circ‐VANGL1 contributes to VANGL1 expression, consequently leading to BC cell proliferation, migration, and invasion. Taken together, our study demonstrated circ‐VANGL1/miR‐605‐3p/VANGL1 as a novel essential signaling pathway involved in BC progression.
A review of the molecular mechanisms of hyperglycemia‐induced free radical generation leading to oxidative stress
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein 
Published: August 2018

AbstractThe prevalence of diabetes is growing worldwide with an increasing morbidity and mortality associated with the development of diabetes complications. Free radical production is a normal biological process that is strictly controlled and has been shown to be important in normal cellular homeostasis, and in the bodies response to pathogens. However, there are several mechanisms leading to excessive free radical production that overcome the normal protective quenching mechanisms. Studies have shown that many of the diabetes complications result from excessive free radical generation and oxidative stress, and it has been shown that chronic hyperglycemia is a potent inducer for free radical production, generated through several pathways and triggering multiple molecular mechanisms. An understanding of these processes may help us to improving our preventive or therapeutic strategies. In this review, the major molecular pathways involved in free radical generation induced by hyperglycemia are described.
Glabridin inhibits osteosarcoma migration and invasion via blocking the p38‐ and JNK‐mediated CREB–AP1 complexes formation
Authors: Jie Zhiwei , Xie Ziang , Zhao Xiangde , Sun Xuewu , Yu Hejun , Pan Xin , Shen Shuying , Qin An , Fang Xiangqian , Fan Shunwu 
Published: August 2018

AbstractOsteosarcoma is the most common bone malignancy, and it seriously affects the quality of life of affected children and adolescents. Glabridin (GLA), a major component of licorice root extract, has been reported to exert antitumor effects against a variety of tumor types; however, its effects on osteosarcoma have not been elucidated. In the current study, we investigate the effects and potential antimetastatic mechanisms of GLA on osteosarcoma in vitro and in vivo. Flow cytometry showed that GLA induced G2/M cell cycle phase arrest and promoted cell apoptosis. Transwell and wound‐healing assays showed that GLA significantly decreased the migration and invasion of osteosarcoma cells. Further western blotting and quantitative real‐time polymerase chain reaction showed that the expression of matrix metalloproteinase (MMP)‐2 and MMP‐9 in MG63 and HOS cells were reduced after GLA treatment. Moreover, western blotting demonstrated that GLA downregulated the phosphorylation of p38 mitogen‐activated protein kinases and c‐Jun N‐terminal kinase. A coimmunoprecipitation assay illustrated that formation of cAMP response element‐binding protein (CREB)–activating protein 1 (AP1) complexes and the DNA binding activities of CREB and AP1 in MG63 and HOS cells were impaired following treatment with GLA. Finally, GLA inhibited tumor growth and suppressed osteosarcoma cell metastasis in vivo. Overall, our findings highlight the potential of GLA as a therapeutic agent for the prevention and treatment of tumor metastasis.
Reduced cardiomyocyte Na+ current in the age‐dependent murine Pgc‐1β−/− model of ventricular arrhythmia
Authors: Ahmad Shiraz , Valli Haseeb , Smyth Robert , Jiang Anita Y. , Jeevaratnam Kamalan , Matthews Hugh R. , Huang Christopher L.‐H. 
Published: August 2018

AbstractPeroxisome proliferator‐activated receptor‐γ coactivator‐1 deficient (Pgc‐1β−/−) murine hearts model the increased, age‐dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch‐clamp techniques in intact young and aged, wild‐type (WT) and Pgc‐1β−/−, ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage‐dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two‐way analysis of variance associated Pgc‐1β−/− genotype with independent reductions in maximum peak ventricular Na+ currents from −36.63 ± 2.14 (n = 20) and −35.43 ± 1.96 (n = 18; young and aged WT, respectively), to −29.06 ± 1.65 (n = 23) and −27.93 ± 1.63 (n = 20; young and aged Pgc‐1β−/−, respectively) pA/μm2 (p < 0.0001), without independent effects of, or interactions with age. Voltages at half‐maximal current V*, and steepness factors k in plots of voltage dependences of both Na+ current activation and inactivation, and time constants for its postrepolarisation recovery from inactivation, remained indistinguishable through all experimental groups. So were the activation and rectification properties of delayed outward (K+) currents, demonstrated from tail currents reflecting current recoveries from respective varying or constant voltage steps. These current–voltage properties directly implicate decreases specifically in maximum available Na+ current with unchanged voltage dependences and unaltered K+ current properties, in proarrhythmic reductions in AP conduction velocity in Pgc‐1β−/− ventricles.