bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac
Authors: Li Yaping , Sun Weixuan , Sun Dajun , Yin Dexin 
Published: February 2019

AbstractRas–extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling has been proposed as the crucial regulators in the development of various cancers. Histone acetylation at H3 lysine 14 (H3K14ac) is closely associated with gene expression and DNA damage. However, whether H3K14ac participates in mediating Ras–ERK1/2‐induced cell proliferation and migration in uveal melanoma cells remains unknown. The purpose of this study is to investigate the effect of H3K14ac on Ras–ERK1/2 affected uveal melanoma cell phenotypes. MP65 cells were transfected with Ras
WT and Ras
G12V/T35S, the unloaded plasmid of pEGFP‐N1 served as a negative control. Protein levels of phosphorylated ERK1/2
Thr202 and H3K14ac were assessed by western blot assay. Cell viability, number of colonies, migration, and the downstream genes of ERK1/2 were analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, soft‐agar colony formation, transwell, and chromatin immunoprecipitation assays. HA‐tag vectors of CLR3 and TIP60 and the small interfering RNAs that specific for CLR3 and MDM2 were transfected into MP65 cells to uncover the effects of CLR3, TIP60, and MDM2 on Ras–ERK1/2 mediated H3K14ac expression and MP65 cell phenotypes. We found that, Ras–ERK1/2 decreased H3K14ac expression in MP65 cells, and H3K14ac significantly suppressed Ras–ERK1/2‐induced cell viability, colony formation, and migration in MP65 cells. Moreover, the transcription of CYR61, IGFBP3, WNT16B, NT5E, GDF15, and CARD16 was regulated by H3K14ac. Additionally, CLR3 silence recovered H3K14ac expression and reversed the effect of Ras–ERK1/2 on MP65 cell proliferation, migration and the mRNAs of ERK1/2 downstream genes. Besides, Ras–ERK1/2 decreased H3K14ac expression by MDM2‐mediated TIP60 degradation. In conclusion, Ras–ERK1/2 promoted uveal melanoma cells growth and migration by downregulating H3K14ac via MDM2‐mediated TIP60 degradation.
Expression pattern of microRNAs related with response to trastuzumab in breast cancer
Authors: Yang Fan , Fu Ziyi , Yang Mengzhu , Sun Chunxiao , Li Yongfei , Chu Jiahui , Zhang Yanhong , Li Wei , Huang Xiang , Li Jun , Wu Hao , Ding Xiaorong , Yin Yongmei 
Published: February 2019

AbstractBackgroundAlthough an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab.MethodsDifferentially expressed miRNAs between trastuzumab‐resistant and trastuzumab‐sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein–protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2‐positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA.ResultsUsing miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab‐resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real‐time PCR confirmed seven miRNAs in cell lines. PI3K‐Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab‐sensitive patients, three miRNAs, namely miR‐200b, miR‐135b, and miR‐29a, were identified to be upregulated, and miR‐224 was downregulated in the trastuzumab‐resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained.ConclusionThe results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab.
Memory and CAR‐NK cell‐based novel approaches for HIV vaccination and eradication
Authors: Mazarzaei Abdulbaset , Vafaei Mahtab , Ghasemian Abdolmajid , Mirforughi Seyede Amene , Rajabi Vardanjani Hassan , Alwan Nada A. S. 
Published: February 2019

AbstractHuman immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV‐infected cells. These cells identify and eliminate virus‐infected cells in a multilateral manner, such as ligand stress, antibody‐dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV‐infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long‐term maintenance of these HIV‐reactive NK cells. CAR‐NK (chimeric antigen receptor‐natural killer) cells‐based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR‐T (chimeric antigen receptor‐T) cells. Recent development of induced pluripotent stem cell (iPSC)‐derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR‐NK cell‐based therapies. Therefore, memory and CAR‐NK cells‐based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.
The overexpression of GRASP might inhibit cell proliferation and invasion in hepatocellular carcinoma
Authors: Cheng Yang , Yin Baobing , Hou Tianlu , Chen Tianyang , Ping Jian 
Published: February 2019

AbstractThis study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC‐related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis‐related genes were identified. A representative DMP was used to divide the DMPs into hyper‐ and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real‐time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5‐Aza‐2′‐deoxycytidine (5‐Aza‐DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit‐8 and transwell assays. Forty‐three HCC prognosis‐related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper‐ and hypomethylated groups, distinguishing between high‐ and low‐risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5‐Aza‐DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G‐CSFR expression. Thus, GRASP might be a prognosis‐related gene controlled by methylation.
Design and synthesis of novel celastrol derivative and its antitumor activity in hepatoma cells and antiangiogenic activity in zebrafish
Authors: Wang Gang , Xiao Qi , Wu Yao , Wei Ying‐jie , Jing Yue , Cao Xiang‐rong , Gong Zhu‐nan 
Published: February 2019

AbstractTwo series of celastrol derivatives were designed and synthesized by modifying carboxylic acid at the 28th position with amino acid, and their intermediates with isobutyrate at the third position. All compounds were evaluated for their antiproliferation activity by four human cancer cell lines (SCG7901, HGC27, HepG2, and Bel7402) and one normal cell LO2. The most promising compound, compound 8, showed superior bioactivity and lower toxicity than others including celastrol. Further underlying tests illustrated that compound 8 induced apoptosis and cell arrest at G2/M and inhibited proliferation and mobility of human hepatoma cells by suppressing the signal transducer and activator of transcription‐3 signaling pathway. Besides these, a highly accurate and reproducible high performance liquid chromatography protocol was established to determine celastrol and compound 8 absorption in zebrafish, and results demonstrated that their concentration increased rapidly within 4 hr in a time‐dependent manner and the concentration of compound 8 was higher than that of celastrol. In addition, without detection at 12 hr, compound 8 was rapidly metabolized in vivo. These findings are very helpful for the structural modification of celastrol and other bioactive compounds to improve their bioactivity, toxicity, and absorption.
Characterization of canine adipose tissue‐derived mesenchymal stem cells immortalized by SV40‐T retrovirus for therapeutic use
Authors: Ayala‐Cuellar Ana Patricia , Kim Cho‐Won , Hwang Kyung‐A , Kang Ji‐Houn , Lee Gabsang , Cho Jaejin , Choi Kyung‐Chul 
Published: February 2019

AbstractCanine mesenchymal stem cells (cMSCs) are gaining popularity in the veterinary field as a regenerative therapy. But, their limited culture lifespan makes it an obstacle for preclinical investigation and therapeutic use. In this study, primary canine adipose tissue‐derived MSCs (PCAT‐MSCs) were isolated from adipose tissue and were transfected with the SV40‐T retrovirus resulting in a life‐extended immortalized canine adipose tissue‐derived MSCs (ICAT‐MSCs). A comparison was made through the characterization of both PCAT‐MSCs and ICAT‐MSCs. Both showed a fibroblastic morphology; ICAT‐MSCs showed a higher potential of colony formation compared with PCAT‐MSCs and a reduced population doubling time; stem cell markers SOX2 and NANOG were expressed in both cell lines; karyotyping analysis showed no abnormalities in both PCAT‐MSCs and ICAT‐MSCs; both cell lines were CD90+, CD44
+, and CD45
−; both generated chondrogenic pellet; in osteogenic differentiation both showed upregulation of Osterix, a master transcriptome of osteogenesis, but in PCAT‐MSCs, an upregulation of SOX2 was also observed. In conclusion, ICAT‐MSCs showed similar characteristics with PCAT‐MSCs, thus established as an easy to access platform for studies on better understanding about cMSCs nature.
The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle
Authors: Salazar Celia , Elorza Alvaro A. , Cofre Glenda , Ruiz‐Hincapie Paula , Shirihai Orian , Ruiz Lina María 
Published: February 2019

AbstractHIG2A promotes cell survival under hypoxia and mediates the assembly of complex III and complex IV into respiratory chain supercomplexes. In the present study, we show that human HIGD2A and mouse Higd2a gene expressions are regulated by hypoxia, glucose, and the cell cycle‐related transcription factor E2F1. The latter was found to bind the promoter region of HIGD2A. Differential expression of the HIGD2A gene was found in C57BL/6 mice in relation to tissue and age. Besides, the silencing of HIGD2A evidenced the modulation of mitochondrial dynamics proteins namely, OPA1 as a fusion protein increases, while FIS1, a fission protein, decreases. Besides, the mitochondrial membrane potential (ΔΨm) increased. The protein HIG2A is localized in the mitochondria and nucleus. Moreover, we observed that the HIG2A protein interacts with OPA1. Changes in oxygen concentration, glucose availability, and cell cycle regulate HIGD2A expression. Alterations in HIGD2A expression are associated with changes in mitochondrial physiology.
miR‐193: A new weapon against cancer
Authors: Khordadmehr Monireh , Shahbazi Roya , Sadreddini Sanam , Baradaran Behzad 
Published: February 2019

AbstractmicroRNAs (miRNAs) are known as a large group of short noncoding RNAs, which structurally consist of 19–22 nucleotides in length and functionally act as one of the main regulators of gene expression in important biological and physiological contexts like cell growth, apoptosis, proliferation, differentiation, movement (cell motility), and angiogenesis as well as disease formation and progression importantly in cancer cell invasion, migration, and metastasis. Among these notable tiny molecules, many studies recently presented the important role of the miR‐193 family comprising miR‐193a‐3p, miR‐193a‐5p, miR‐193b‐3p, and miR‐193b‐5p in health and disease biological processes by interaction with special targeting and signaling, which mainly contribute as a tumor suppressor. Therefore, in the present paper, we review the functional role of this miRNA family in both health and disease conditions focusing on various tumor developments, diagnoses, prognoses, and treatment.
Beyond esterase‐like activity of serum albumin. Histidine‐(nitro)phenol radical formation in conversion cascade of p‐nitrophenyl acetate and the role of infrared light
Authors: Kowacz Magdalena , Warszyński Piotr 
Published: February 2019

AbstractSerum albumin, recognized mainly for its capacity to act as a carrier protein for many compounds, can also actively transform some organic molecules. As a starting point in this study, we consider esterase‐like activity of bovine serum albumin (BSA) toward p‐nitrophenyl acetate (p‐NPA). Our results reveal that the reaction goes beyond ester hydrolysis step. In fact, the transformation product, p‐nitrophenol (p‐NP), becomes a substrate for further reaction with BSA in which its nitro group in subtracted and released in the form of HNO2. Spectral data indicate that this cascade of events proceeds through formation of phenoxyl radical via proton‐coupled electron transport (PCET) between OH group of p‐NP and imidazole ring of histidine from the protein. Furthermore, the effect of application of electromagnetic radiation in the infrared range suggests that this remote physical trigger can support interactions based on PCET mechanism by acting on polarization and mutual alignment of water dipoles serving as effective water wires.
Building blocks for thoracic MRI: Challenges, sequences, and protocol design
Authors: Raptis Constantine A. , Ludwig Daniel R. , Hammer Mark M. , Luna Antonio , Broncano Jordi , Henry Travis S. , Bhalla Sanjeev , Ackman Jeanne B. 
Published: February 2019

Thoracic MRI presents important and unique challenges. Decreased proton density in the lung in combination with respiratory and cardiac motion can degrade image quality and render poorly executed sequences uninterpretable. Despite these challenges, thoracic MRI has an important clinical role, both as a problem‐solving tool and in an increasing array of clinical indications. Advances in scanner and sequence design have also helped to drive this development, presenting the radiologist with improved techniques for thoracic MRI. Given this evolving landscape, radiologists must be familiar with what thoracic MR has to offer. The first step in developing an effective thoracic MRI practice requires the creation of efficient and malleable protocols that can answer clinical questions. To do this, radiologists must have a working knowledge of the MR sequences that are used in the thorax, many of which have been adapted from use elsewhere in the body. These sequences can be broadly divided into three categories: traditional/anatomic, functional, and cine based. Traditional/anatomic sequences allow for the depiction of anatomy and pathologic processes with the ability for characterization of signal intensity and contrast enhancement. Functional sequences, including diffusion‐weighted imaging, and high temporal resolution dynamic contrast enhancement, allow for the noninvasive measurement of tissue‐specific parameters. Cine‐based sequences can depict the motion of structures in the thorax, either with retrospective ECG gating or in real time. The purpose of this article is to review these categories, the building block sequences that comprise them, and identify basic questions that should be considered in thoracic MRI protocol design.Level of Evidence: 5Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2019;50:682–701.
Application of neurite orientation dispersion and density imaging to characterize brain microstructural abnormalities in type‐2 diabetics with mild cognitive impairment
Authors: Xiong Ying , Zhang Shuoqi , Shi Jingjing , Fan Yang , Zhang Qiang , Zhu Wenzhen 
Published: February 2019

BackgroundDiffusion‐tensor‐imaging (DTI) is sensitive in detecting white matter changes in type‐2 diabetes mellitus (T2DM). However, DTI indices can be affected by either neurite density or spatial variation. A novel diffusion MRI technique, termed neurite orientation dispersion and density imaging (NODDI), can provide distinct indices of fiber density and dispersion.PurposeTo characterize brain microstructural alterations in T2DM patients with mild cognitive impairment (MCI) using the NODDI model.Study TypeCross‐sectional.SubjectsTwenty T2DM patients with (DM‐MCI group), 18 age‐ and gender‐matched T2DM patients with normal cognition (DM‐NC group), and 28 euglycemic healthy controls (HC).Field Strength/Sequence3T/NODDI.AssessmentDiffusion data were analyzed using tract‐based‐spatial‐statistics (TBSS) analysis in white matter and voxel‐based analysis in both white and gray matter. NODDI indices, including intracellular volume fraction (Vic) and orientation dispersion index (ODI), were estimated from multiple regions and compared among these groups.Statistical TestsDifferences between groups were compared by Student's t‐test, Pearson chi‐square test, or analysis of variance when appropriate. Correlation analyses were performed to investigate the relationship between NODDI variables and clinical measurements.ResultsWhole‐brain TBSS revealed that 2.29% and 2.02% of the white matter regions exhibited decreased fractional anisotropy and Vic, respectively, between the DM‐NC and HC, while considerably larger white matter areas showed decreased fractional anisotropy (38.38%) and Vic (34.64%) between the DM‐MCI and HC (Student's t‐test, P < 0.05). However, the angular variation of neurites, characterized by ODI, exhibited very little (0.1%, P < 0.05) or no difference (P > 0.05) between either the DM‐MCI or DM‐NC groups and HC. Decreased Vic values in the genu of the corpus callosum (R = 0.580, 0.551 and 0.586, P < 0.01) and thalamus (R = 0.570, 0.616, and 0.595, P < 0.05) correlated with glycosylated hemoglobin A1c level, disease duration, and neuropsychological scores, respectively.Data ConclusionT2DM patients with cognitive decline had reduced Vic, which indicated decreased density of axons and dendrites. NODDI might be able to help probe microstructural changes in white and gray matter and provide information on diabetic encephalopathy, including those with cognitive impairment.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:889–898.
Can cells maintain their bioactivity in ionic liquids? A novel single‐cell assessment by Raman microspectroscopy
Authors: Matsuda Ami , Sakaguchi Naoko , Shigeto Shinsuke 
Published: February 2019

AbstractIonic liquids (ILs) are widely exploited in numerous applications in chemistry, biology, and materials science. Assessment of the toxicity of ILs is thus urgently needed to develop genuinely “green” ILs that do not pose hazards to the environment and humans. Despite considerable efforts mostly with cell viability assays, little has been understood about how, at the molecular level, ILs affect the bioactivity and intracellular chemistry of single individual cells. Here, we report a new method based on Raman microspectroscopy for quantitatively examining the effects of ILs on the bioactivity of single living fission yeast cells beyond just counting viable cells. The ILs studied are two hydrophilic ILs, 2‐hydroxyethyl‐trimethylammonium l‐(+)‐lactate [Cho][Lac] and 1‐ethyl‐3‐methylimidazolium acetate [emim][AcO], and they were mixed with liquid medium. We used a characteristic yeast Raman band at 1,602 cm−1, which sharply reflects the bioactivity of yeast cells. For both ILs, the Raman spectra measured at lipid droplets in IL‐treated yeast cells clearly exhibited the 1,602‐cm−1 band, indicating that yeast cells can indeed maintain their bioactivity in the ILs. Furthermore, we observed that the amide I peak in the cytoplasmic/nuclear Raman spectrum significantly blueshifts in [emim][AcO] compared with that in the normal medium and [Cho][Lac]. This unexpected finding suggests an IL‐induced change in protein secondary structure from α‐helix to β‐sheet and random‐coil structures. The present study not only demonstrates that Raman microspectroscopy utilizing the 1,602‐cm−1 band of yeast is a unique, powerful tool for single‐cell assessment of IL toxicity, but it also calls attention to the effects of ILs on the structure and hence functions of intracellular molecules that might have been overlooked in previous studies.
Peptides from Mucuna pruriens L., with protection and antioxidant in vitro effect on HeLa cell line
Authors: Martínez‐Leo Edwin E , Martín‐Ortega Armando M , Acevedo‐Fernández Juan J , Moo‐Puc Rosa , Segura‐Campos Maira R 
Published: February 2019

AbstractBACKGROUNDMucuna pruriens L. is a legume sown in the Mexican southeast with an important protein content. Studies have shown the potential use of by‐products derived from Mucuna as a functional food because of the hypoglycemic and antihypertensive activities. Thus, this study aims to assess the antioxidant and protective effect of the peptide fractions derived from M. pruriens L., in vitro on the HeLa cell line. An enzymatic hydrolysis with pepsin–pancreatin was performed on the total protein concentrate, from which five peptide fractions were obtained.RESULTSAll protein derivatives from M. pruriens L., except F5–10 kDa, decreased the hydrogen peroxide production by more than 50%. The highest antioxidant activity was exhibited by F1–3 kDa, which lowered the intracellular reactive oxygen species by 207 ± 4.20%. No significant differences were found in the protective effects of the protein hydrolysate, F5–10 kDa, F3–5 kDa and F1–3 kDa relative to the N‐acetylcysteine control group.CONCLUSIONThis elucidated the potential action mechanisms of M. pruriens L. protein derivatives for future investigations and their role in the prevention and treatment of oxidative stress. © 2019 Society of Chemical Industry
Mutation status and surgical selection
Authors: Margonis Georgios A , Kreis Martin E , Wolfgang Christopher L , Weiss Matthew J 
Published: February 2019

AbstractCurrent evidence cannot support denying metastasectomy in otherwise resectable patients solely based on their overall KRAS or BRAF mutational status. The combination of KRAS or BRAF mutational status with certain clinicopathologic characteristics has defined groups of patients who may not derive benefit from metastasectomy, but external validation is needed. The effect of certain KRAS or BRAF variants on survival may be more pronounced and therefore future studies should consider them for surgical selection.