bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold‐Catalyzed Enantioselective Intramolecular Annulation of Ene‐Yne‐Carbonyls via Benzopyrylium‐Type Intermediates
Authors: Koshikawa Takumi , Satoh Masakazu , Masutomi Koji , Shibata Yu , Tanaka Ken
Published: November 2018

It has been established that a cationic gold(I)/(R)‐H8‐binap complex catalyzes the enantioselective intramolecular [4+2] annulation of benzene‐linked ene‐yne‐carbonyls via benzopyrylium‐type intermediates at room temperature to give chiral tricyclic compounds, bearing two stereogenic centers, as single diastereomers with moderate ee values. Interestingly, the reactions of sterically demanding naphthalene‐linked ene‐yne‐carbonyls with the same gold(I) catalyst gave not only [4+2] annulation products but also [3+2] annulation products as minor products with good ee values.
Geochemistry, Petrology, and U–Pb dating of high‐K volcanic rocks in wells WC‐1 and Y‐2 from the northern Junggar Basin, northwestern China: Implications for the closure of the Keramaili oceanic basin during the Carboniferous
Authors: Han Sijie , Sang Shuxun , Liang Jingjing , Wang Wenfeng , Zhang Guanlong , Wang Shengzhu
Published: November 2018

Carboniferous volcanic rocks are widely distributed in the Junggar Basin and may provide a unique insight into the tectonic history of this basin. In this paper, we focus on the tectonic evolution of the northern Junggar Basin (NJB) using geochronological and geochemical data to establish the diachronous closure model for the Keramaili oceanic basin. The Lower Carboniferous strata in the eastern part (well WC‐1) and the Upper Carboniferous strata in the western part (well Y‐2) of the NJB are composed of a mix of compositional and rock‐type forms. These volcanic rocks are mostly high‐K assemblages characterized by high K (1.73–6.48%), high alkali (Na2O + K2O = 5.04–7.45%), and low TiO2 (0.57–1.06%). They also exhibit various REE concentrations (68.44–168.19 ppm), an enrichment of LREE (LaN/YbN = 4.54–8.09), and small negative Eu anomalies (δEu = 0.74–0.90). The depletion of HFSE and relevant tectonic setting discrimination diagrams demonstrate that these two volcanic associations were formed in a subduction‐related environment. The data also indicate that the high‐K volcanic rocks are derived from a mix of melted subducted sediments and mantle metasomatized by silica‐rich fluids. Although these two sets of volcanic rocks formed in Early and Late Carboniferous, the similar petrographic and geochemical natures suggest similar magma source and tectonic setting. Along with different regional tectonic settings in the NJB during the Carboniferous, we propose an asynchronous subduction of Keramaili oceanic basin, resulting in the inconsistent temporal and spatial distribution of Upper Carboniferous volcanic rocks in the NJB.
Neoarchean suprasubduction zone magmatism in the Sonakhan greenstone belt, Bastar Craton, India: Implications for subduction initiation and melt extraction
Authors: Manu Prasanth M.P. , Hari K.R. , Chalapathi Rao N.V. , Santosh M. , Hou Guiting , Tsunogae Toshiaki , Pandit Dinesh
Published: November 2018

The Neoarchean Sonakhan greenstone belt (SGB) in the north‐eastern Bastar Craton is mainly composed of an association of pillowed and massive tholeiitic basalts emplaced within an intraoceanic environment. Two types of ultrabasic rocks were identified and are designated as TH‐1 and TH‐2 on the basis of geochemical parameters. Both sample suites exhibit depletion of HFSE with reference to LILE and LREE, LREE/HFSE ratios, and negative Nb–Ta–Ti anomalies in the primitive mantle‐normalized multi‐element diagrams. The geochemical characters of TH‐1 and TH‐2 are consistent with Island arc tholeiites (IAT) and boninite‐like rocks of both Archean and Phanerozoic terranes. Mineral chemistry of clinopyroxenes from both volcanic suites indicate an oceanic arc affinity. The chromite chemistry indicate its derivation from a boninite‐like magma in a suprasubduction zone (SSZ) environment. Trace element modelling depicts that source depletion with significant influence of fluids derived from the subducting oceanic slab collectively controlled the trace element inventory of the mantle wedge, which result to the higher abundance of LREE and LILE compared to HREE and HFSE. The occurrence of lower basalt sequence followed by IAT and boninite‐like rocks in the SGB define a magmatic evolution which is comparable to the Phanerozoic ophiolite suites that exhibit subduction initiation prior to forearc rifting and suprasubduction zone magmatism. The subduction initiation in the intraoceanic lithosphere and the initial decompression melting followed by the upwelling of the MORB‐related magmas were attributed to the formation of the lower pillow basalts. Dehydration of the subducting plate and the melt extraction processes in the hydrous lherzolite mantle wedge account for the formation of TH‐1. Subsequent depletion and significant modification of a more refractory harzburgite source by the slab‐derived fluids generated the TH‐2 rocks. The compositionally diverse magmatic imprints with IAT and boninite affinity in the SGB indicate the significance of episodic melt extraction processes, dehydration of the subducting plate, and hydrous fluxing in SSZ tectonic setting.
miR‐30a‐5p inhibition promotes interaction of Fas+endothelial cells and FasL+microglia to decrease pathological neovascularization and promote physiological angiogenesis
Authors: Murinello Salome , Usui Yoshihiko , Sakimoto Susumu , Kitano Maki , Aguilar Edith , Friedlander H. Maura , Schricker Amelia , Wittgrove Carli , Wakabayashi Yoshihiro , Dorrell Michael I. , Westenskow Peter D. , Friedlander Martin
Published: November 2018

Ischemia‐induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti‐VEGF agents but are not successful in all cases. In this study we determined that miR‐30a‐5p is another important mediator of retinal angiogenesis. Using a rodent model of ischemic retinopathy, we show that inhibiting miR‐30a‐5p reduces neovascularization and promotes tissue repair, through modulation of microglial and endothelial cell cross‐talk. miR‐30a‐5p inhibition results in increased expression of the death receptor Fas and CCL2, to decrease endothelial cell survival and promote microglial migration and phagocytic function in focal regions of ischemic injury. Our data suggest that miR‐30a‐5p inhibition accelerates tissue repair by enhancing FasL–Fas crosstalk between microglia and endothelial cells, to promote endothelial cell apoptosis and removal of dead endothelial cells. Finally, we found that miR‐30a levels were increased in the vitreous of patients with proliferative diabetic retinopathy. Our study identifies a role for miR‐30a in the pathogenesis of neovascular retinal disease by modulating microglial and endothelial cell function, and suggests it may be a therapeutic target to treat ischemia‐mediated conditions.
Childhood Fructoholism and Fructoholic Liver Disease
Authors: Ribeiro Andreia , Igual‐Perez Maria‐Jose , Santos Silva Ermelinda , Sokal Etienne M.
Published: November 2018

Nonalcoholic fatty liver disease (NAFLD) is an emerging entity, becoming the most prevalent pediatric chronic liver disease. Its broad spectrum of histological findings, comorbidities, and complications, including cirrhosis and liver failure, can occur in childhood, emphasizing the severity of pediatric NAFLD. Current lifestyle and diet modifications have been linked to the increasing prevalence of NAFLD, including the rise of fructose consumption, a monosaccharide present in foods that contain added sugar, such as sugar‐sweetened beverages. Excessive fructose consumption is believed to cause addiction like alcohol and other drugs. As such, the new term “fructoholism” refers to the consumption of a substance (fructose) that can cause psychological and physical damage and become a major public health concern, highlighting the seriousness of the excessive consumption of fructose in the pediatric age. Hepatic fructose metabolization leads to hepatic steatosis and progression to fibrosis through mechanisms comparable to alcoholic liver disease, hence the term “fructoholic liver disease.” Conclusion: The importance of implementing reliable global strategies, such as education campaigns to promote healthy diet, increasing taxes on foods that contain added sugars, subsidies to promote accessibility to fruit and vegetables, and strict food industry regulation to reduce sugar intake in children and adolescents, cannot be overemphasized.
Work stress and the risk of cancer: A meta‐analysis of observational studies
Authors: Yang Tingting , Qiao Yan , Xiang Siyun , Li Wenzhen , Gan Yong , Chen Yongchun
Published: November 2018

Epidemiological studies have explored the relationship between work stress and the risk of cancer, but it remains unclear on whether work stress could increase the risk of cancer, or by other factors such as smoking and physical activity. Our study aimed to investigate the association between work stress and the risk of cancer and in relation to major potential confounding and modifying factors. We systematically searched three electronic databases, hand‐searched references and citations of retrieved articles, and consulted experts to identify studies on assessing the association between work stress and the risk of cancer. The relative risks (RRs) of cancer associated with work stress were estimated using a random‐effects model, and stratified by exposure measurement, study design, gender, study location, cancer site, smoking, drinking, body mass index, and physical activity. A total of 281,290 participants were included in this analysis. The significant association between work stress and the risk of colorectal (RR = 1.36; 95%CI: 1.16–1.59), lung (RR = 1.24; 95%CI: 1.02–1.49), and esophagus (RR = 2.12; 95%CI: 1.30–3.47) cancers were found. A statistically significant effect of work stress on colorectal cancer risk was observed in North America (RR = 1.51, 95% CI: 1.23–1.86, but not significant in Europe (RR = 1.16, 95% CI: 0.90–1.48). By contrast, a significant association between work stress and esophagus cancer was found in Europe, but not in North America. In addition, we did not observe any association between work stress and the risk of prostate, breast, or ovarian cancers. Findings of our study show that work stress is an important risk factor for colorectal, lung, and esophagus cancers. General public should be aware of the increased risk of cancer in employers with work stress. More efforts should be focused on understanding and studying the potential mechanisms which would help to identify employees at higher risk of these cancers.
Laminin γ2‐enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via integrin α3‐dependent uptake by lymphatic endothelial cells
Authors: Wang Ssu‐Han , Liou Gunn‐Guang , Liu Szu‐Heng , Chang Jeffrey S. , Hsiao Jenn‐Ren , Yen Yi‐Chen , Chen Yu‐Lin , Wu Wan‐Ling , Chang Jang‐Yang , Chen Ya‐Wen
Published: November 2018

Oral squamous cell carcinoma (OSCC) LN1‐1 cells previously showed greater capacities for lymphangiogenesis and lymph node metastasis compared to their parental OEC‐M1 cells, in addition to an ability to enhance the migration and tube formation of lymphatic endothelial cells (LECs). Purified by a series of differential centrifugations and characterized using electron microscopy, dynamic light scattering and western blot, LN1‐1 cell‐derived extracellular vesicles (LN1‐1 EVs) were shown to promote LEC migration, tube formation and uptake by LECs more effectively than did OEC‐M1 cell‐derived EVs (OEC‐M1 EVs). Using stable isotope labeling with amino acids in cell culture/liquid chromatography–tandem mass spectrometry‐based proteomic platform, the laminin‐332 proteins, including laminin α3, β3 and γ2, were validated as highly expressed proteins in LN1‐1 EVs. Clinically, a higher level of laminin‐332 was detected in plasma EVs from OSCC patients with lymph node metastasis than in both healthy controls and OSCC patients without lymphatic metastasis, suggesting EV‐borne laminin‐332 as a novel and noninvasive biomarker for the detection of lymph node metastasis in OSCC. The knockdown of laminin γ2 and inhibition by anti‐laminin‐332 neutralizing antibodies impaired LN1‐1 EV‐mediated LEC migration, tube formation and uptake by LECs. Importantly, laminin γ2‐deficient EVs showed a reduced ability to drain into lymph nodes in comparison with the control EVs. In addition, the laminin 332/γ2‐mediated EV uptake was dependent on integrin α3 but not β1, β4 or α6. Collectively, the uptake of laminin γ2‐enriched EVs by LECs enhanced in vitro lymphangiogenesis and EV‐borne laminin‐332 is thus a viable biomarker for OSCC.
Is high vitamin B12 status a cause of lung cancer?
Authors: Fanidi Anouar , Carreras‐Torres Robert , Larose Tricia L. , Yuan Jian‐Min , Stevens Victoria L. , Weinstein Stephanie J. , Albanes Demetrius , Prentice Ross , Pettinger Mary , Cai Qiuyin , Blot William J. , Arslan Alan A. , Zeleniuch‐Jacquotte Anne , McCullough Marjorie L. , Le Marchand Loic , Wilkens Lynne R. , Haiman Christopher A. , Zhang Xuehong , Stampfer Meir J. , Smith‐Warner Stephanie A. , Giovannucci Edward , Giles Graham G. , Hodge Allison M. , Severi Gianluca , Johansson Mikael , Grankvist Kjell , Langhammer Arnulf , Brumpton Ben M. , Wang Renwei , Gao Yu‐Tang , Ericson Ulrika , Bojesen Stig E. , Arnold Susanne M. , Koh Woon‐Puay , Shu Xiao‐Ou , Xiang Yong‐Bing , Li Honglan , Zheng Wei , Lan Qing , Visvanathan Kala , Hoffman‐Bolton Judith , Ueland Per M. , Midttun Øivind , Caporaso Neil E. , Purdue Mark , Freedman Neal D. , Buring Julie E. , Lee I‐Min , Sesso Howard D. , Michael Gaziano J. , Manjer Jonas , Relton Caroline L. , Hung Rayjean J. , Amos Chris I. , Johansson Mattias , Brennan Paul ,   on behalf of the LC3 consortium and the TRICL consortium
Published: November 2018

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
Highlights in Chemical Glycobiology
Authors: Wong Chi‐Huey , Krasnova Larissa
Published: November 2018

The advances of chemical biology have provided means for a better understanding of complex biological systems at the molecular level as well as solutions to the problems associated with the complex systems. The interdisciplinary approach of chemical biology was also embraced by the research in glycoscience as illustrated in this essay with some of the relevant examples from our group.
Focally amplified lncRNA on chromosome 1 regulates apoptosis of esophageal cancer cells via DRP1 and mitochondrial dynamics
Authors: Liu Tao , Wang Zhi , Zhou Riqiang , Liang Wulin
Published: November 2018

Long noncoding RNAs (lncRNAs), a family of noncoding RNA transcripts with a length of <200 nucleotides (nts), have been associated with the pathological development of various types of carcinogenesis. Focally amplified lncRNA on chromosome 1 (FAL1) is a recently identified lncRNA. In the current study, we aimed to investigate the physiological function of FAL1 in esophageal squamous cell carcinoma (ESCC). Our findings demonstrate that FAL1 was associated with esophageal cancer cell survival by regulating mitochondrial fission. First, we found that the expression of the mitochondrial fission protein dynamin‐related protein 1 (DRP1) was significantly reduced, but the expression of the mitochondrial fusion protein mitofusin 1 (Mfn1) was increased in ESCC tissues and esophageal cancer cell lines as compared with adjacent normal tissues and a normal esophagus epithelial cell line. In addition, we found that reduced expression of DRP1 in the esophageal cancer cell lines KYSE450 and EC9706 cells was associated with increased expression of FAL1. Inhibition of FAL1 promoted mitochondrial fission and mitochondrial dysfunction in KYSE450 and EC9706 cells mediated by DRP1. Silencing of DRP1 abolished FAL1‐induced apoptosis through a mitochondrial‐dependent pathway. Our findings suggest that FAL1/DRP1 could be a therapeutic target for the treatment of ESCC. © 2018 IUBMB Life, 71(1):254–260, 2019
Regulatory role of vitamin E in the immune system and inflammation
Authors: Lewis Erin Diane , Meydani Simin Nikbin , Wu Dayong
Published: November 2018

Vitamin E, a potent lipid‐soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell‐based, pre‐clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α‐tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non‐α‐alpha‐tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487–494, 2019
Cigarette smoke extract may induce lysosomal storage disease‐like adverse health effects
Authors: Park Eun‐Jung , Park Yoo‐Jin , Lee Sang Jin , Yoon Cheolho , Lee Kyuhong
Published: November 2018

Cigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH‐S, a mouse alveolar macrophage cell line. CSE decreased cell viability accompanying increased lactate dehydrogenase release. Additionally, mitochondrial volume and the potential increased along with enhanced expression of mitochondrial fusion proteins and decreased adenosine triphosphate production. Similarly, CSE clearly induced increase of catalase activity and intracellular calcium concentration and decrease of endoplasmic reticulum and lysosome volume at the highest dose. More interestingly, damaged organelles accumulated in the cytosol, and CSE‐containing particles specifically penetrated to mitochondria. Meanwhile, any significant change in autophagy related protein expression was not found in CSE‐treated cells. Subsequently, we evaluated the effects of CSE on secretion of inflammatory related cytokines and chemokines, considering the relationship between organelle damage and the disturbed immune response. Very importantly, we found that expression of innate and adaptive immunity related mediators is disrupted following CSE exposure. Taken together, we suggest that CSE may cause the accumulation of damaged organelles in the cytoplasm by impairing selective autophagic function. In addition, this accumulation is responsible for the inadequate ability of immune cells to repair the damage of lung tissue following exposure to CSE.
The use of cobalt chloride as a chemical hypoxia model
Authors: Muñoz‐Sánchez Jorge , Chánez‐Cárdenas María E.
Published: November 2018

The use of hypoxia models in cell culture has allowed the characterization of the hypoxia response at the cellular, biochemical and molecular levels. Although a decrease in oxygen concentration is the optimal hypoxia model, the problem faced by many researchers is access to a hypoxia chamber or a CO2 incubator with regulated oxygen levels, which is not possible in many laboratories. Several alternative models have been used to mimic hypoxia. One of the most commonly used models is cobalt chloride‐induced chemical hypoxia because it stabilizes hypoxia inducible factors 1α and 2α under normoxic conditions. This model has several advantages, and currently, there is a substantial amount of scattered information about how this model works. This review describes the characteristics of the model, as well as the biochemical and molecular bases that support it. The regulation of hypoxia inducible factors by oxygen and the role of CoCl2 are explained to understand the most accepted bases of the CoCl2‐induced hypoxia model. The different current hypotheses that explain the establishment of hypoxic conditions using CoCl2 are also described. Finally, based on the different observations reported in the literature, we provide a critical review about the scope and limitations of this widely used chemical hypoxia model to be informative to all researchers interested in the field.
Increasing fluorescence lifetime for resolution improvement in stimulated emission depletion nanoscopy
Authors: Wang Lu‐Wei , Chen Yue , Yan Wei , Weng Xiao‐Yu , Yang Zhi‐Gang , Ye Tong , Qu Jun‐Le
Published: November 2018

Super‐resolution microscopy (SRM) has had a substantial impact on the biological sciences due to its ability to observe tiny objects less than 200 nm in size. Stimulated emission depletion (STED) microscopy represents a major category of these SRM techniques that can achieve diffraction‐unlimited resolution based on a purely optical modulation of fluorescence behaviors. Here, we investigated how the laser beams affect fluorescence lifetime in both confocal and STED imaging modes. The results showed that with increasing illumination time, the fluorescence lifetime in two kinds of fluorescent microspheres had an obvious change in STED imaging mode, compared with that in confocal imaging mode. As a result, the reduction of saturation intensity induced by the increase of fluorescence lifetime can improve the STED imaging resolution at the same depletion power. The phenomenon was also observed in Star635P‐labeled human Nup153 in fixed HeLa cells, which can be treated as a reference for the synthesis of fluorescent labels with the sensitivity to the surrounding environment for resolution improvement in STED nanoscopy.
Endothelin‐1 triggers human peritoneal mesothelial cells’ proliferation via ERK1/2‐Ets‐1 signaling pathway and contributes to endothelial cell angiogenesis
Authors: Zhu Nan , Gu Lijie , Jia Jieshuang , Wang Xuan , Wang Ling , Yang Man , Yuan Weijie
Published: November 2018

Background

Dysfunction of the peritoneum as a dialysis organ may result from progressive membrane injury on peritoneal dialysis (PD). It has been increasingly recognized that the human peritoneal mesothelial cells (HPMCs) play a key role in peritoneal membrane early injury. Recently, it has been reported that bioincompatible PD fluid with high concentrations of glucose and glucose degradation products, low pH, high osmolality, and peritonitis stimulates HPMCs to release endothelin‐1 (ET‐1). ET‐1 causes increased the release of vascular endothelial growth factor, which is important for tumor cell angiogenesis. We hypothesized that activating ET‐1 might predict injury of peritoneal membrane.

Methods

HPMCs were isolated from normal omentum. ERK1/2 and Ets‐1 phosphorylation were measured by Western blot analysis. HPMC proliferation was detected by the bromodeoxyuridine (BrdU) assay. Capillary networks of tubes formed were photographed under a microscope, and five randomly selected fields from each well were analyzed for total capillary length by using Image J software.

Results

MEK‐1 blocker significantly abolished the ERK1/2 activation by ET‐1, which also triggered phosphorylation, thus activating the transcription factor Ets‐1 downstream from ERK1/2. ET‐1 was capable to induce HPMC proliferation, which could be attenuated by ET‐1 antagonists. Antibody and small interfering RNA mediated blockade of Ets‐1 had similar antiproliferative effects. Thus, ET‐1 specifically triggered HPMC proliferation via ERK1/2‐Ets‐1 signaling pathway. VEGF production and endothelial cell angiogenesis were significantly in response to conditioned medium from HPMCs treated with ET‐1.

Conclusions

ET‐1 triggered HPMC proliferation through the ERK1/2‐Ets‐1 signaling pathway and contributed to VEGF production and endothelial cell angiogenesis.
MicroRNA‐338‐3p inhibits tumor growth and metastasis in osteosarcoma cells by targeting RUNX2/CDK4 and inhibition of MAPK pathway
Authors: Jia Feng , Zhang Zhen , Zhang Xu
Published: November 2018

Osteosarcoma (OS) is one of the most aggressive bone tumors. MicroRNAs (miRNAs) have been found to implicate in the pathogenesis of different types of cancers, including OS. This study aimed to explore the roles of miR‐338‐3p in OS and investigate the underlying mechanism. Human OS cell lines (MG‐63 and U2OS) and osteoblast (hFOB) cell line were used in the study. The expression levels of miR‐338‐3p, runt‐related transcription factor 2 (RUNX2) and cyclin‐dependent kinase 4 (CDK4) were altered by transient transfection and determined by quantitative real‐time polymerase chain reaction/Western blot analysis. Cell viability, colony numbers, migration, and invasion, and apoptotic cells were measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, colony formation assay, transwell assay, and flow cytometry assay, respectively. Dual luciferase reporter assay was performed to identify the target gene of miR‐338‐3p. Western blot assay was carried to measure the protein expression levels involved in cell apoptosis, migration, and mitogen‐activated protein kinases (MAPK) pathway. We found that the expression of miR‐338‐3p was downregulated in MG‐63 cell and U2OS cells, compared with hFOB cells. MiR‐338‐3p suppression significantly increased cell viability and colony numbers, promoted cell migration, and invasion, but suppressed cell apoptosis in MG‐63 and U2OS cells. Opposite results were observed in the miR‐338‐3p overexpression. Interestingly, RUNX2 and CDK4 were direct target genes of miR‐338‐3p. RUNX2 inhibition shared a similar effect of miR‐338‐3p mimic on MG‐63 cells. Furthermore, miR‐338‐3p inhibited the activation of MAPK pathway in MG‐63 cells. To conclude, these findings suggested that miR‐338‐3p functioned as a tumor suppressor in OS cells by targeting RUNX2 and CDK4, as well as inhibition of the MAPK pathway.
lncRNA nuclear‐enriched abundant transcript 1 promotes cell proliferation and invasion by targeting miR‐186‐5p/HIF‐1α in osteosarcoma
Authors: Tan Hongyu , Zhao Liang
Published: November 2018

Increasing evidence shows that the long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) plays important roles in tumor progression. However, the function and the underlying mechanism of NEAT1 in osteosarcoma (OS) remain unclear. In the present study, we found that NEAT1 expression was significantly upregulated in OS tissues and cell lines. High NEAT1 expression was closely associated with advanced clinicopathologic features and poor overall survival of patients with OS. Using in vitro function assay, we found that NEAT1 could promote the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) process of OS cells. NEAT1 could also promote OS cell growth in vivo. In addition, our studies showed that miR‐186‐5p was a downstream target of NEAT1 in OS. Functionally, miR‐186‐5p suppressed the proliferation, invasion, and EMT process of OS cells. Furthermore, our data revealed that HIF‐1α was a downstream target of miR‐186‐5p and that NEAT1 could exert its tumor oncogenic roles on OS cells via the miR‐186‐5p/HIF‐1α axis. Taking our results together, we elucidated that the NEAT1/miR‐186‐5p/HIF‐1α axis might be a therapeutic approach for the treatment of OS.
Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1‐1 inhibitor, in tumorigenesis and tumor progression
Authors: Ozcan Mehmet , Esendagli Gunes , Musdal Yaman , Canpinar Hande , Bacanlı Merve , Anlar Hatice Gul , Esendağlı‐Yılmaz Güldal , Beyramzadeh Mojtaba , Aksoy Yasemin
Published: November 2018

Glutathione (GSH) and enzymes related to this antioxidant molecule are often overexpressed in tumor cells and may contribute to drug resistance. Blockade of glutathione transferases (GSTs) has been proposed to potentiate the efficacy of chemotherapeutic drugs in cancer. The aim of this study was to evaluate the effect of chlorophyllin that has antioxidant properties, and also interferes with the activity of GST P1‐1, on breast cancers in vitro and in vivo. The in vivo studies were conducted using an N‐methyl‐
N‐nitrosourea (MNU)‐induced chemical carcinogenesis model in laboratory rats. DNA damage, GST activity, and GSH levels were determined in liver and tumor tissues. Treatment with chlorophyllin increased the GSH levels in the liver and significantly decreased DNA damage in the blood, liver, and tumor tissues. Even though tumorigenesis was delayed in rats receiving chlorophyllin before MNU injections, once the tumors emerged, the progression of tumor appeared to be faster than in the animals that received the carcinogen only. Out of nine breast cell lines, GST P1‐1 expression was detected in MCF‐12A, MDA‐MB‐231, and HCC38. Concomitant incubation with chlorophyllin and docetaxel did not significantly affect cell proliferation and viability. Chlorophyllin displayed genoprotective effects that initially delayed tumorigenesis. However, once the tumors were established, it may act as a promoter that facilitates tumor growth, potentially by a mechanism independent of cell proliferation and viability. Our results underline the pros and cons of antioxidant treatment in cancer, even if it has a capacity to inhibit GST P1‐1.
Expression of circulating miR‐17, miR‐25, and miR‐133 in breast cancer patients
Authors: Hesari AmirReza , Azizian Mitra , Darabi Hassan , Nesaei Abolfazl , Hosseini Seyede Atefe , Salarinia Reza , Motaghi Amir Ali , Ghasemi Faezeh
Published: November 2018

One of the most lethal cancers among women is breast cancer. MicroRNAs (miRNAs) can be of great importance in the early detection of breast cancer. This study aimed to investigate some miRNAs in the serum of patients with breast cancer compared with the control group. Total RNA was extracted from the serum of patients with breast cancer and healthy volunteers. The expression levels of miRNAs and the genes were assessed using real‐time reverse transcriptase‐polymerase chain reaction with specific primers. Our data showed that miR‐25 and miR‐133 were downregulated, and miR‐17 was upregulated in patients with breast cancer. Upregulation of miR‐17 is related to the poor survival time and increased cell proliferation. The reduced expression of miR‐133 and miR‐25 is significantly associated with clinical stage, metastasis, and survival time of patients with breast cancer. Expressions of miRNAs miR‐17, miR‐25, and miR‐133 are altered in patients with clinical stage, metastasis, poor survival time.
The discovery of a novel eight‐mRNA‐lncRNA signature predicting survival of hepatocellular carcinoma patients
Authors: Shi Ye‐Min , Li Yan‐Yan , Lin Jia‐Yun , Zheng Lei , Zhu Yi‐Ming , Huang Jian
Published: November 2018

Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non‐coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA‐lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA‐lncRNA signature to improve the ability to predict HCC patients’ survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high‐risk group and low‐risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648‐6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well‐performed nomogram integrating the prognostic signature and other clinical information to predict 3‐ and 5‐year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA‐lncRNA may be an efficient classification tool to evaluate the prognosis of patients’ with HCC.
The comparative study of the effects of Fe2O3 and TiO2 micro‐ and nanoparticles on oxidative states of lung and bone marrow tissues and colony stimulating factor secretion
Authors: Soltani Arash , Kahkhaie Kolsoum Rezaie , Haftcheshmeh Saeed Mohammadian , Jalali Nezhad Ahmad Ali , Akbar Boojar Masoud Mashhadi
Published: November 2018

Nowadays, increased use of nanomaterials in industry and biomedicine poses potential risks to human health and the environment. Studying their possible toxicological effects is therefore of great significance. The present investigation was designed to examine the status of oxidative stress induced by nanoparticles (NPs) of ferric oxide (Fe2O
3) and titanium oxide (TiO
2) with their micro‐sized counterpart on mouse lung and bone marrow–derived normal tissue cells. We assessed the induction of oxidative stress by measuring its indicators such as antioxidant scavenging activity of superoxide dismutase and catalase as well as malondialdehyde concentration. Moreover, colony formation of bone marrow cells was assayed following induction with colony stimulating factor (CSF) from lung cells. NPs had a more potent stimulatory effect on the oxidative stress status than their micron‐sized counterparts. In addition, the highest level of oxidative stress derived from TiO
2 NPs was observed in both tissue types. Cotreatment with NPs and the antioxidant α‐tocopherol reduced antioxidant activities and membrane lipid peroxidation (LPO) in the lung cells, but increased CSF‐induced colony formation activity of bone marrow cells, suggesting that oxidative stress may be the cause of the cytotoxic effects of NPs. It is concluded that free radicals generated following exposure to NPs resulted in signiﬁcant oxidative stress in mouse cells, indicated by increased LPO and antioxidant enzyme activity and decreased colony formation.
Identification of potentially critical genes in the development of heart failure after ST‐segment elevation myocardial infarction (STEMI)
Authors: Qian Cheng , Chang Danqi , Li Hang , Wang Yanggan
Published: November 2018

Heart failure (HF) remains a common complication after acute ST‐segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post‐infarct HF and eight patients without post‐infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non‐HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein‐protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow‐up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix‐receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post‐infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.
How hsa‐miR‐495 performed in the tumorigenesis of pancreatic adenocarcinoma by bioinformatics analysis
Authors: Yang Yuemei , Wang Yanfeng , Liu Shizhong , Zhao Xiaoling , Jia Rujing , Xiao Yu , Zhang Ming , Li Xiaoou , Li Ji , Wang Wenze
Published: November 2018

Introduction

Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world for early metastasis, extensive invasion, and poor prognosis with a 5‐year survival rate less than 5%. However, the underlying mechanisms are poorly understood. Therefore, it is urgent to explore molecular markers for early diagnosis or therapy target to improve the outcome of PAAD.

Methods

We retrieved transcriptome data as well as clinical information from patients with PAAD in The Cancer Genome Altas (TCGA) database. Survival time associated microRNAs (miRNAs) and messenger RNAs (mRNAs) were initially identified, followed by enrichment analysis (Gene Ontology [GO] and pathway). The relationship between survival time associated miRNAs‐mRNAs was also investigated to discover putative transcriptional control mechanisms of PAAD. Finally, by consulting the literature and retrieving the database, we found that hsa‐miR‐495 might have played an important role in PAAD.

Results

In total, 146 miRNAs from 378 miRNAs and 580 mRNA from 17 100 mRNA, including 328 risk mRNA and 252 protective mRNA, were found to be associated with the survival time of PAAD. Eight hundred eighty‐eight mRNA‐miRNA pairs were related to the survival time of PAAD, involving in 755 mRNAs and 35 miRNAs. We chose 13 miRNAs predicted by target gene in the miRanda database for further research. Among these 13 miRNAs, hsa‐miR‐495 was identified as a good biomarker. Through GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significantly enriched pathways involved in focal adhesion, Staphylococcus aureus infection, and Intestinal immune network for immunoglobulin A production. And four target genes and 87 pathways of the hsa‐miR‐495 were enriched in PAAD. Interestingly, we found hsa‐miR‐495 with a low expression having a poor overall survival and significantly different recurrence rate within 5 years.

Conclusion

Hsa‐miR‐495 and its target genes may serve as a prognostic and predictive marker in PAAD. Further research on the function of the hsa‐miR‐495 and its target genes in the KEGG pathway may provide references for treatment of PAAD.
miR‐145 is a potential biomarker for predicting clinical outcome in glioblastomas
Authors: Shi Lei , Wang Bin , Gu Xiaoyan , Zhang Shuguang , Li Xiaoliang , Zhu Haifeng
Published: November 2018

miR‐145 has been found to be significantly downregulated in gliomas, and overexpression of miR‐145 increases glioma cell apoptosis and enhances chemosensitivity or herpes simplex virus thymidine kinase gene therapy. However, the correlation between miR‐145 and the clinical prognosis of glioblastomas has never been explored. In this study, a retrospective study was conducted in 86 cases of patients with glioblastoma after neurosurgery combined with chemoradiotherapy, and 36 cases with traumatic brain injury. Our results showed that miR‐145 was significantly lower in glioblastoma tissues than that in normal brain tissue (P < 0.05). Furthermore, miR‐145 was lower in patients with lower Karnofsky Performance Scale (KPS) scores than in patients with higher KPS scores (
P < 0.05). Cox Regression analysis showed that low miR‐145 expression was associated with poor patient survival (
P < 0.05). These data suggested that patients with glioblastoma with lower miR‐145 expression are prone to shorter overall survival.
Acetyl‐coenzyme A acyltransferase 2 promote the differentiation of sheep precursor adipocytes into adipocytes
Authors: Zhang Yani , Wang Yingjie , Wang Xiaoyan , Ji Yanqin , Cheng Shaoze , Wang Man , Zhang Chen , Yu Xinjian , Zhao Ruifeng , Zhang Wenhui , Jin Jing , Li Tingting , Zuo Qisheng , Li Bichun
Published: November 2018

The acetyl CoA acyltransferase 2 (ACAA2) is a key enzyme of the fatty acid oxidation pathway, catalyzing the last step of the mitochondrial beta oxidation, thus playing an important role in the fatty acid metabolism. The purpose of this study was to investigate the effect of knocking out ACAA2 on the expression of genes lipoprteinlipase (LPL), peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), fatty acid synthase, fat mass and obesity‐associated gene, adipocyte fatty acid‐binding protein (AP2) in precursor adipocytes and their differentiation into adipocytes. The knockout vector was constructed using CRISPR‐Cas RNA‐guided nuclease technology with an efficiency of 23.80%, and the vector was transfected into precursor adipocyte cells, while an overexpression vector of the ACAA2 gene was also transfected in another group of preadipocytes. Quantitative polymerase chain reaction showed that the expression of the PPAR‐γ, LPL, and AP2 was significantly lower in the knockout compared with the overexpression group, while there was no difference in cell growth. After induction of adipocyte precursor cells into adipocytes using dexamethasone, insulin, and IBMX, oil red staining showed a significantly different number of lipid droplets in the knockout group. These results provide a preliminary indication for a possible involvement of the ACAA2 gene in adipocyte differentiation in vitro.
Retracted: Combined therapy using LHRH‐PE40 and anti‐CD40 dendritic cells substantially eliminate tumor cells
Authors: Zhang Limin , Du TianJiao , Ma DongBin , Guo Fang , Li ZhenWei , Yan Hua
Published: November 2018

LHRH‐PE40 was used to promote the proliferation of bone marrow derived cell (BMDC) and improve the antigen‐presenting ability of BMDC as well as the immune function via the CD40 signal pathway. LHRH‐PE40 was also implicated in cancer treatment, targeting a variety of cancer cells that express luteinizing hormone‐releasing hormone receptor (LHRHR). In the present study, the mechanism and efficacy of LHRH‐PE40 were addressed in the following three aspects. Enzyme‐linked immunosorbent assay was performed to confirm the binding specificity of LHRH‐PE40 to LHRHR. The killing effect of LHRH‐PE40 on target cells was mediated by LHRHR, which specifically killed LHRHR‐positive target cells while the minimal cytotoxicity of LHRHR‐negative cells is negligible. Spiegelmers, a molecule mutually exclusive with GnRH and developed by Sven Klussmann and Dr Sven Klussmann of NOXXON Pharmaceuticals in Germany, demonstrated that LHRH‐PE40 maintains a combinatory characteristics of LHRH and LHRHR. In the end, the mechanism of LHRH‐PE40 underlying induction of apoptosis at low concentration and prolonged conditions was firstly demonstrated by the basic method of detecting apoptosis to induce apoptosis. It provided a scientific basis for clinical application of LHRH‐PE40 and laid a foundation for the further study of LHRH‐PE40 on inducing apoptosis of target cells. The target cells herein refer to tumor cells that overexpress LHRHR. This study shows that activated DC can more effectively promote the proliferation of CD4+ T cells, and initially proved that DC carrying anti‐CD40 antibody promoted the immune treatment of the tumor. Combining LHRH‐PE40 with anti‐CD40 DCs achieved substantially improved efficacy in killing tumor cells.
Long noncoding RNA LINC00968 promotes endothelial cell proliferation and migration via regulating miR‐9‐3p expression
Authors: Wang Xiaofeng , Zhao Zheng , Zhang Wei , Wang Yi
Published: November 2018

Long noncoding RNAs (lncRNAs) have been showed to play a crucial role in pathogenesis and development of cardiovascular diseases. Our study aimed to study the expression and functional role of lncRNA LINC00968 in the development of coronary artery disease (CAD). We showed that the LINC00968 expression level was upregulated in the CAD tissues compared with normal arterial tissues. In addition, we showed that the expression level of LINC00968 was upregulated by oxidized low‐density lipoprotein (oxLDL) treatment in endothelial cell. Ectopic expression of LINC00968 regulated the proliferation and migration of endothelial cell. Moreover, we showed that overexpression of LINC00968 inhibited miR‐9‐3p expression in an endothelial cell. Furthermore, we demonstrated that the miR‐9‐3p expression was downregulated in the CAD samples compared with normal arterial tissues and the expression level of miR‐9‐3p was downregulated by oxLDL treatment in endothelial cell. Finally, we showed that ectopic expression of LINC00968 promoted endothelial cell proliferation and migration partly through regulating miR‐9‐3p expression. These results suggested that LINC00968 plays a crucial role in the progression of the CAD.