bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to target energy metabolism in consensus molecular subtype 3 along with Kirsten rat sarcoma viral oncogene homolog mutations for colorectal cancer therapy
Authors: Wang Gang , Wang Jun‐Jie , Yin Pei‐Hao , Xu Ke , Wang Yu‐Zhu , Shi Feng , Gao Jing , Fu Xing‐Li 
Published: October 2018

AbstractAlterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the deﬁnition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)‐activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.
Cyclooxygenase‐2 in cancer: A review
Authors: Hashemi Goradel Nasser , Najafi Masoud , Salehi Eniseh , Farhood Bagher , Mortezaee Keywan 
Published: October 2018

AbstractCyclooxygenase‐2 (COX‐2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo‐ and radiotherapy. COX‐2 is released by cancer‐associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX‐2 induces cancer stem cell (CSC)‐like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX‐2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX‐2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX‐2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX‐2 on cancer cells or its regulation. Members of mitogen‐activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor‐κβ are main upstream modulators for COX‐2 in cancer cells. COX‐2 also has interactions with a number of hormones within the body. Inhibition of COX‐2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX‐2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX‐2 inhibition also sensitizes cancer cells to treatments like radio‐ and chemotherapy. Chemotherapeutic agents adversely induce COX‐2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX‐2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.
Signatures of altered long noncoding RNAs and messenger RNAs expression in the early acute phase of spinal cord injury
Authors: Shi Zhongju , Ning Guangzhi , Zhang Bin , Yuan Shiyang , Zhou Hengxing , Pan Bin , Li Jiahe , Wei Zhijian , Cao Fujiang , Kong Xiaohong , Feng Shiqing 
Published: October 2018

AbstractSpinal cord injury (SCI) is a highly severe disease and it can lead to the destruction of the motor and sensory function resulting in temporary or permanent disability. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt that play a critical role in central nervous system (CNS) injury. However, the exact roles of lncRNAs and messenger RNAs (mRNAs) in the early acute phase of SCI remain to be elucidated. We examined the expression of mRNAs and lncRNAs in a rat model at 2 days after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. Subsequently, a comprehensive bioinformatics analysis was also performed to clarify the interaction between DE mRNAs. A total of 3,193 DE lncRNAs and 4,308 DE mRNAs were identified between the injured group and control group. Classification, length distribution, and chromosomal distribution of the dysregulated lncRNAs were also performed. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. A protein−protein interaction (PPI) network indicated that IL6, TOP2A, CDK1, POLE, CCNB1, TNF, CCNA2, CDC20, ITGAM, and MYC were the top 10 core genes. The subnetworks from the PPI network were identified to further elucidate the most significant functional modules of the DE mRNAs. These data may provide novel insights into the molecular mechanism of the early acute phase of SCI. The identification of lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for SCI.
Wnt lipidation: Roles in trafficking, modulation, and function
Authors: Hosseini Vahid , Dani Christian , Geranmayeh Mohammad Hossein , Mohammadzadeh Fatemeh , Nazari Soltan Ahmad Saeed , Darabi Masoud 
Published: October 2018

AbstractThe Wnt signaling pathway consists of various downstream target proteins that have substantial roles in mammalian cell proliferation, differentiation, and development. Its aberrant activity can lead to uncontrolled proliferation and tumorigenesis. The posttranslational connection of fatty acyl chains to Wnt proteins provides the unique capacity for regulation of Wnt activity. In spite of the past belief that Wnt molecules are subject to dual acylation, it has been shown that these proteins have only one acylation site and undergo monounsaturated fatty acylation. The Wnt monounsaturated fatty acyl chain is more than just a hydrophobic coating and appears to be critical for Wnt signaling, transport, and receptor activation. Here, we provide an overview of recent findings in Wnt monounsaturated fatty acylation and the mechanism by which this lipid moiety regulates Wnt activity from the site of production to its receptor interactions.
Circ‐U2AF1 promotes human glioma via derepressing neuro‐oncological ventral antigen 2 by sponging hsa‐miR‐7‐5p
Authors: Li Guoxiong , Huang Min , Cai Yingqian , Yang Yuantao , Sun Xinlin , Ke Yiquan 
Published: October 2018

AbstractThe prognosis for human glioma, a malignant tumor of the central nervous system, is poor due to its rapid growth, genetic heterogeneity, and inadequate understanding of its underlying molecular mechanisms. Circular RNAs composed of exonic sequences, represent an understudied form of noncoding RNAs (ncRNAs) that was discovered more than a decade ago, function as microRNA sponges. We aimed to assess the relationship between circ‐U2AF1 (CircRNA ID: hsa_circ_0061868) and hsa‐mir‐7‐5p and examine their effects on proliferation, apoptosis, and the metastatic phenotype of glioma cells regulated by neuro‐oncological ventral antigen 2 (NOVA2). We found that the expression levels of circ‐U2AF1 and NOVA2 were upregulated, while hsa‐miR‐7‐5p was downregulated in human glioma tissues and glioma cell lines. Our data and bioinformatic analysis indicated the association of these molecules with glioma grade, a positive correlation between circ‐U2AF1 and NOVA2 expression levels and a negative correlation of hsa‐miR‐7‐5p with both circ‐U2AF1 and NOVA2, respectively. In addition, silencing of circ‐U2AF1 expression resulted in increased hsa‐miR‐7‐5p expression and decreased NOVA2 expression both in vitro and in vivo. Luciferase assay confirmed hsa‐miR‐7‐5p as a direct target of circ‐U2AF1 and NOVA2 as a direct target of hsa‐miR‐7‐5p. Functionally, silencing of circ‐U2AF1 inhibits glioma development by repressing NOVA2 via upregulating hsa‐miR‐7‐5p both in vitro and in vivo. Thus, we assumed that circ‐U2AF1 promotes glioma malignancy via derepressing NOVA2 by sponging hsa‐miR‐7‐5p. Taken together, we suggest that circ‐U2AF1 can be a prognostic biomarker and the circ‐U2AF1/hsa‐miR‐7‐5p/NOVA2 regulatory pathway may be a novel therapeutic target for treating gliomas.
Obtaining scratch‐free specimens of dental enamel prepared by sectioning, grinding, polishing, and acid etching for scanning electron microscopy
Authors: Risnes Steinar , Li Chunfang 
Published: October 2018

AbstractThe aim of the present study was to identify the stage during acid etching of dental enamel where scratches introduced by sectioning and grinding procedures were eliminated. Nitric acid was used as etchant. Four hundred 2–3 mm‐thick longitudinal sections of human third molar crowns were assigned to 80 groups, each group differing with respect to grinding procedure (silicon carbide paper grit 600; 1,000; 1,200; and 1,200 + polishing), acid concentration (0.1%, 1%, 2.5%, and 5%) and etching time (15, 30, 45, 90, and 180 s). Observation of the specimens with scanning electron microscopy (SEM) showed that elimination of scratches was facilitated by increasing fineness of grinding paper and polishing, and by increasing acid concentration and increasing etching time. An acid concentration of 0.1% did not remove scratches totally irrespective of grinding procedure or etching time, 1% acid removed most scratches after 45–90 s, while 2.5% and 5% acids removed most scratches after 30–45 s. It is proposed that the scratches are eliminated/obscured through a combined effect of the acid and the inherent structure of the enamel. The results of the present study may serve as a guide in choosing the best procedures for obtaining scratch‐free enamel surfaces through acid etching with the least possible loss of enamel substance.Research highlights
Sectioning and grinding produce scratches in dental enamel.
Scratches are eliminated by acid etching prior to SEM studies of enamel structure.
Scratch elimination increases with increasing acid strength and etching time and is facilitated by finer grit grinding paper and polishing.
Radiosynthesis of O‐(1‐[18F]fluoropropan‐2‐yl)‐O‐(4‐nitrophenyl)methylphosphonate: A novel PET tracer surrogate of sarin
Authors: Hayes Thomas R. , Thompson Charles M. , Blecha Joseph E. , Gerdes John M. , VanBrocklin Henry F. 
Published: October 2018

O‐(1‐Fluoropropan‐2‐yl)‐O‐(4‐nitrophenyl) methylphosphonate is a reactive organophosphate ester (OP) developed as a surrogate of the chemical warfare agent sarin that forms a similar covalent adduct at the active site serine of acetylcholinesterase. The radiolabeled O‐(1‐[18F]fluoropropan‐2‐yl)‐O‐(4‐nitrophenyl) methylphosphonate ([18F] fluorosarin surrogate) has not been previously prepared. In this paper, we report the first radiosynthesis of this tracer from the reaction of bis‐(4‐nitrophenyl) methylphosphonate with 1‐[18F]fluoro‐2‐propanol in the presence of DBU. The 1‐[18F]fluoro‐2‐propanol was prepared by reaction of propylene sulfite with Kryptofix 2.2.2 and [18F] fluoride ion. The desired tracer O‐(1‐[18F]fluoropropan‐2‐yl)‐O‐(4‐nitrophenyl) methylphosphonate was obtained in a >98% radiochemical purity with a 2.4% ± 0.6% yield (n = 5, 65 minutes from start of synthesis) based on starting [18F] fluoride ion and a molar activity of 49.9 GBq/μmol (1.349 ± 0.329 Ci/μmol, n = 3). This new facile radiosynthesis routinely affords sufficient quantities of [18F] fluorosarin surrogate in high radiochemical purity, which will further enable the tracer development as a novel radiolabeled OP acetylcholinesterase inhibitor for assessment of OP modes of action with PET imaging in vivo.
Nicotine impairs intra‐substance tendon healing after full thickness injury in a rat model
Authors: Cheema Adnan N. , Newton Joseph B. , Boorman‐Padgett James F. , Weiss Stephanie N. , Nuss Courtney A. , Gittings Daniel J. , Farber Daniel C. , Soslowsky Louis J. 
Published: October 2018

ABSTRACTNicotine is harmful to many bodily systems; however, the effects of nicotine on intra‐substance tendon healing remain largely unexplored. The purpose of this study was to examine the functional, structural, and biomechanical effects of nicotine on the healing of Achilles tendons in rats after an acute full‐thickness injury. Sixty Sprague‐Dawley rats were enrolled in this study. Half were exposed to 0.9% saline and half to 61 ng/mL of nicotine for 3 months via subcutaneous osmotic pumps. At 3 months, all rats underwent blunt full thickness transection of the left Achilles tendon and were immobilized for one week in plantarflexion. In‐vivo assays were conducted prior to injury, at 21 days, and at 42 days post‐injury and included the following: Functional limb assessment, passive joint mechanics, and vascular evaluation. Rats were sacrificed at 21 and 42 days for biomechanical testing and histologic evaluation. Rats exposed to nicotine demonstrated decreased vascularity, greater alteration in gait mechanics, and increased passive ROM of the ankle joint. Biomechanically, the nicotine tendons failed at lower maximum loads, were less stiff, had smaller cross‐sectional areas and had altered viscoelastic properties. Histologically, nicotine tendons demonstrated decreased vessel density at the injury site. This study demonstrates that nicotine leads to worse functional outcomes and biomechanical properties in tendons. The decreased vascularity in the nicotine group may suggest an underlying mechanism for inferior tendon healing. Patients should be counseled that using nicotine products increase their risk of poor tendon healing and may predispose them to tendon re‐rupture. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Stimulated Raman scattering microscopy with long wavelengths for improved imaging depth
Authors: Moester Miriam J.B. , Zada Liron , Fokker Bart , Ariese Freek , de Boer Johannes F. 
Published: October 2018

AbstractStimulated Raman scattering (SRS) imaging is a fast, label‐free, and sensitive technique to map the distribution of a vibrational species in a microscopy setting. It has great potential for applications in many fields, such as lipid imaging in biomedicine. However, depth penetration of the light into the sample is an issue with any light‐based technique, especially with multiphoton techniques such as SRS. Using longer wavelengths allows deeper penetration into densely scattering materials, but applying wavelengths above 1,500 nm is challenging technically. We have built a flexible SRS microscope system capable of imaging with a combination of 1,064 nm and wavelengths over 1,500 nm, using the idler output of an optical parametric oscillator (OPO). For comparison, the same system was also operated in the more common configuration, using 1,064 nm in combination with the OPO signal output around 800 nm. With the long‐wavelength settings, we show improved depth penetration in polyethylene plastic material and in a silicone phantom with embedded polymer microbeads, and we report images of lipid structure in biological tissue. These results demonstrate the technical feasibility of using these long wavelengths for SRS imaging. Disadvantages such as poorer spatial resolution and lower signal strength are also discussed. The application of this new approach to SRS microscopy can allow greater insight into deep‐lying structures in a non‐invasive way.
Motion‐robust reconstruction of multishot diffusion‐weighted images without phase estimation through locally low‐rank regularization
Authors: Hu Yuxin , Levine Evan G. , Tian Qiyuan , Moran Catherine J. , Wang Xiaole , Taviani Valentina , Vasanawala Shreyas S. , McNab Jennifer A. , Daniel Bruce A. , Hargreaves Brian L. 
Published: October 2018

PurposeThe goal of this work is to propose a motion robust reconstruction method for diffusion‐weighted MRI that resolves shot‐to‐shot phase mismatches without using phase estimation.MethodsAssuming that shot‐to‐shot phase variations are slowly varying, spatial‐shot matrices can be formed using a local group of pixels to form columns, in which each column is from a different shot (excitation). A convex model with a locally low‐rank constraint on the spatial‐shot matrices is proposed. In vivo brain and breast experiments were performed to evaluate the performance of the proposed method.ResultsThe proposed method shows significant benefits when the motion is severe, such as for breast imaging. Furthermore, the resulting images can be used for reliable phase estimation in the context of phase‐estimation‐based methods to achieve even higher image quality.ConclusionWe introduced the shot–locally low‐rank method, a reconstruction technique for multishot diffusion‐weighted MRI without explicit phase estimation. In addition, its motion robustness can be beneficial to neuroimaging and body imaging.
The influence of tightening regulations on patients with new psychoactive substance‐related disorders in Japan
Authors: Tanibuchi Yuko , Matsumoto Toshihiko , Funada Daisuke , Shimane Takuya 
Published: October 2018

AbstractAimsThis study aimed to investigate the influence of tightened regulations on new psychoactive substances in patients with disorders related to these drugs in Japan.MethodsWe used a biennial nationwide survey on drug‐related psychiatric disorders to examine why individuals who had previously used new psychoactive substances as their primary drug (the drug that had the greatest impact on their psychiatric symptoms) had switched to other drugs, how they had used drugs in the last 12 months and what type of drugs they were now using. We compared the clinical features of these individuals with patients who mainly used new psychoactive substances and had used these drugs at least once in the last 12 months.ResultsA total of 2262 people were included, and 399 had used new psychoactive substances. Of those, 71 people had switched to another drug as primary drug, mostly stimulant drugs (35.2%), hypnotics and anxiolytics (15.5%), and cannabis (14.1%) and used these drugs during the previous 12 months. The majority, 53.3%, had switched “because new psychoactive substances were no longer available.” In total, 25 people mainly used new psychoactive substances. The group that had changed drugs had more experience of using methamphetamine and were more likely to have abused other drugs before using new psychoactive substances. They had often switched to illegal or prescription drugs after regulations had been tightened.ConclusionThe number of patients abusing new psychoactive substances decreased after drug regulations were tightened, but new psychoactive substances‐related problems still exist. It is therefore not enough to tighten regulations. Drug dependence treatment and recovery support are also needed.
Exposure to hot and cold environments increases noradrenaline release in the bed nucleus of the stria terminalis in rats
Authors: Minami Saki , Nomura Hiroshi , Minami Masabumi 
Published: October 2018

AbstractAimsThermoregulatory responses in homeothermic animals, including humans, are classified into involuntary autonomous and voluntary behavioral thermoregulatory responses. Although behavioral thermoregulatory responses are probably driven by positive (pleasant) and/or negative (unpleasant) emotions, the neuronal mechanisms underlying the induction of negative emotions by hot and cold environments remain poorly understood. The bed nucleus of the stria terminalis is a brain region implicated in stress responses and negative emotions, such as fear, anxiety, and aversion. Various stimuli that cause negative emotions, such as immobilization stress, fox odor, gastric distension, and inflammatory pain, increase noradrenaline release in the rat bed nucleus of the stria terminalis, especially in the ventral bed nucleus of the stria terminalis. It has been reported that the negative emotional component of pain is mediated by noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis. However, the role of intra‐ventral bed nucleus of the stria terminalis noradrenergic neurotransmission in the induction of negative emotion by exposure to hot and cold environments remains to be elucidated. For the first step to address this issue, the effects of hot and cold environments on noradrenaline release in the ventral bed nucleus of the stria terminalis were examined.MethodsIn vivo microdialysis analyses in unanesthetized, freely moving male Sprague‐Dawley rats were performed to examine hot and cold environments‐induced noradrenaline release in the ventral bed nucleus of the stria terminalis.ResultsExposure to hot (38°C) and cold (8°C) environments significantly increased noradrenaline release in the ventral bed nucleus of the stria terminalis.ConclusionsThe results suggest that exposure to hot and cold environments enhances noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis, which may induce negative emotion, and thereby drive avoidance behaviors, that is, escape from hot and cold environments.
Double‐networks based on interconnected amphiphilic “in–out” star first polymer conetworks prepared by RAFT polymerization
Authors: Kitiri Elina N. , Varnava Constantina K. , Patrickios Costas S. , Voutouri Chrysovalantis , Stylianopoulos Triantafyllos , Gradzielski Michael , Hoffmann Ingo 
Published: October 2018

ABSTRACTDouble‐network hydrogels were prepared using well‐defined first networks comprising interconnected amphiphilic “in‐out” star copolymers synthesized via sequential reversible addition‐fragmentation chain transfer (RAFT) polymerization, and second networks based on a photopolymerized mixture of acrylamide and N,N′‐methlyenebisacrylamide. All first and double‐network hydrogels were characterized in terms of their aqueous degrees of swelling and mechanical properties in compression. The most hydrophobic first and double‐network hydrogels exhibited the best mechanical properties, which may be attributed to their low aqueous swelling degrees and good mesoscale organization in water as revealed using small‐angle neutron scattering (SANS) which showed that the size of the formed hydrophobic domains could be controlled by the polymer conetwork structure. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2161–2174