bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning approach for homolog chromosome classification
Authors: Somasundaram Devaraj 
Published: August 2018

AbstractAutomated analysis of human chromosomes is a necessary procedure to attain karyotyping and it is highly effective in cytology analysis to detect birth defects in metaspread chromosomes. In this, chromosomes are partitioned into “abnormal” and “normal” categories. However, the success of most traditional classification methods relies on the presence of accurate chromosome segmentation. Despite many years of research in this field, accurate segmentation and classification remains a challenge in the presence of cell clusters and pathologies. Many classification methods focused on hand crafted features, such as length, centromere positions. In this manuscript, proposed method focused on chromosome classification based on deep features using convolutional neural network. It is subsequently trained on various chromosome datasets consisting of adaptively resampled image patches. In the testing phase, average the prediction scores of a similar set of image patches is performed. The proposed method is evaluated on different overlapped, nonoverlapped chromosomes and normal, abnormal datasets. Proposed method better performs than previous algorithms in classification accuracy with 98.7%, area under the curve AUC is 0.97 values, and abnormality detection accuracy is 98.4%.
Evidence for Lgr6 as a Novel Marker of Osteoblastic Progenitors in Mice
Authors: Khedgikar Vikram , Lehoczky Jessica A 
Published: August 2018

ABSTRACTBone marrow–derived mesenchymal stem cells are an important source of osteoblasts critical for both bone homeostasis and repair. The ability to isolate, or specifically target, mesenchymal stem cells committed to the osteogenic lineage is necessary for orthopedic translational therapy efforts; however the precise molecular signature of these cells remains elusive. Previously, we identified a population of osteoprogenitor cells expressing the Wnt signaling agonist Lgr6, which contributes to the development and regeneration of the mouse digit tip bone. In our present study we build upon this data and investigate the expression of Lgr6 more broadly in the skeleton. We find that Lgr6, and closely related Lgr4, are expressed in mouse primary calvarial cells, bone marrow cells, and bone marrow–derived mesenchymal stem cells. In addition, our data demonstrates that Lgr4 expression is modestly increased throughout the differentiation and mineralization of mesenchymal stem cells. In contrast, we find Lgr6 expression to be strikingly increased upon osteogenic induction and subsequently decreased upon differentiation and mineralization. These findings provide evidence for Lgr6 as a novel marker of osteoprogenitor cells in bone marrow, which could prove useful for isolation of this population toward future research and clinical applications. © 2018 American Society for Bone and Mineral Research
Continuing Challenges in Advancing Preclinical Science in Skeletal Cell-Based Therapies and Tissue Regeneration
Authors: Featherall Joseph , Robey Pamela G , Rowe David W 
Published: August 2018

ABSTRACT

Cell-based therapies hold much promise for musculoskeletal medicine; however, this rapidly growing field faces a number of challenges. Few of these therapies have proven clinical benefit, and an insufficient regulatory environment has allowed for widespread clinical implementation without sufficient evidence of efficacy. The technical and biological complexity of cell-based therapies has contributed to difficulties with reproducibility and mechanistic clarity. In order to aid in addressing these challenges, we aim to clarify the key issues in the preclinical cell therapy field, and to provide a conceptual framework for advancing the state of the science. Broadly, these suggestions relate to: (i) delineating cell-therapy types and moving away from “catch-all” terms such as “stem cell” therapies; (ii) clarifying descriptions of cells and their processing; and (iii) increasing the standard of in vivo evaluation of cell-based therapy experiments to determining cell fates. Further, we provide an overview of methods for experimental evaluation, data sharing, and professional society participation that would be instrumental in advancing this field. © 2018 American Society for Bone and Mineral Research.
Silencing CTGF/CCN2 inactivates the MAPK signaling pathway to alleviate myocardial fibrosis and left ventricular hypertrophy in rats with dilated cardiomyopathy
Authors: Hong Lang , Lai Heng‐Li , Fang Yan , Tao Yu , Qiu Yun 
Published: August 2018

AbstractDilated cardiomyopathy (DCM) is characterized by left ventricular dilation associated with systolic dysfunction. The purpose of the current study is to clarify the effect of connective tissue growth factor (CTGF/CCN2) on myocardial fibrosis and left ventricular hypertrophy (LVH) of rats with DCM through the mitogen‐activated protein kinase (MAPK) signaling pathway. First, DCM rat models were established and sh‐CTGF/CCN2 lentiviral expression vectors were constructed. Then, by observing the pathological changes and myocardial ultrastructure as well as detecting cardiac functions, myocardial fibrosis, and LVH of rats, the effect of CTGF/CCN2 gene silencing on rats with DCM was investigated. To further explore how CTGF/CCN2 gene silencing affects rats with DCM, the expression of CTGF/CCN2 and the related genes of the MAPK signaling pathway was detected. Sh‐CTGF/CCN2‐2 and sh‐CTGF/CCN2‐3 with lower CTGF/CCN2 expression were selected for further experimentation. CTGF/CCN2 gene silencing improved cardiac function and alleviated myocardial fibrosis and LVH of rats with DCM. It was also verified that CTGF/CCN2 gene silencing could relieve the pathology of rats with DCM by inactivation of the MAPK signaling pathway. We conclude that CTGF/CCN2 gene silencing inhibits the activation of the MAPK signaling pathway, thus decreases myocardial fibrosis and LVH, and then improves the pathological symptoms of DCM in rats.
GW0742 activates peroxisome proliferator‐activated receptor δ to reduce free radicals and alleviate cardiac hypertrophy induced by hyperglycemia in cultured H9c2 cells
Authors: Cheng Kai‐Chun , Chang Wei‐Ting , Li Yingxiao , Cheng Yung‐Ze , Cheng Juei‐Tang , Chen Zhih‐Cherng 
Published: August 2018

AbstractPeroxisome proliferator‐activated receptor δ (PPARδ), the predominant PPAR subtype in the heart, is known to regulate cardiac function. PPARδ activation may inhibit cardiac hypertrophy in H9c2 cells while the potential mechanism has not been elucidated. Then, H9c2 cells incubated with high glucose to induce hypertrophy were used to investigate using GW0742 to activate PPARδ. The fluorescence assays were applied to determine the changes in cell size, cellular calcium levels, and free radicals. Western blot analyses for hypertrophic signals and assays of messenger RNA (mRNA) levels for hypertrophic biomarkers were performed. In H9c2 cells, GW0742 inhibited cardiac hypertrophy. In addition, increases in cellular calcium and hypertrophic signals, including calcineurin and nuclear factor of activated T‐cells, were reduced by GW0742. This reduction was parallel to the decrease in the mRNA levels of biomarkers, such as brain/B‐type natriuretic peptides and β‐myosin heavy chain. These effects of GW0742 were dose‐dependently inhibited by GSK0660 indicating an activation of PPARδ by GW0742 to alleviate cardiac hypertrophy. Moreover, free radicals produced by hyperglycemia were also markedly inhibited by GW0742 and were later reversed by GSK0660. GW0742 promoted the expression of thioredoxin, an antioxidant enzyme. Direct inhibition of reactive oxygen species by GW0742 was also identified in the oxidant potassium bromate stimulated H9c2 cells. Taken together, these findings suggest that PPARδ agonists can inhibit free radicals, resulting in lower cellular calcium for reduction of hypertrophic signaling to alleviate cardiac hypertrophy in H9c2 cells. Therefore, PPARδ activation can be used to develop agent(s) for treating cardiac hypertrophy.
The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer
Authors: Qiu Han , Kong Jun , Cheng Yunfei , Li Gang 
Published: August 2018

AbstractObjectivesTo clarify the clinical relevance of ubiquitin‐specific protease 8 (USP8) for patients with breast cancer (BC).MethodsPrevious BC microarray studies GSE37751, GSE7390, and GSE21653 were reanalyzed to determine the USP8 levels between BC patients and the corresponding normal breast tissues and the correlation between USP8 expression and clinical features and clinical outcomes of patients with BC. Gene set enrichment analysis (GSEA) was conducted to investigate the potential mechanisms.ResultsUSP8 was downregulated in BC cells compared with that in normal breast tissues (P < 0.0001). The Χ2 test and logistic regression analysis demonstrated that patients in USP8 high‐expression group were correlated with better clinical features (including histopathological grading, estrogen receptors, clinical risk group according to Nottingham prognostic index [NPI] criteria and clinical risk group according to Veridex signature) compared with patients in USP8 low‐expression group. Kaplan‐Meier survival and Cox proportional regression analysis suggested that USP8 predicted better survivals of BC patients in terms of distant metastasis‐free survival, time to distant metastasis, disease‐free survival, and overall survival. GSEA suggested that USP8 might impact the proliferation of BC cells through several biological processes associated tumorigenesis of BC. USP8 was significantly downregulated in BC patients (P < 0.0001).ConclusionsOur results demonstrated that USP8 might predict better clinical characteristics and might be a protective factor for patients with BC.
Identification of therapeutic effect of glucagon‐like peptide 1 in the treatment of STZ‐induced diabetes mellitus in rats by restoring the balance of intestinal flora
Authors: Yuan Xiao , Ni Haixiang , Chen Xialiang , Feng Xiaohong , Wu Qiaomin , Chen Jie 
Published: August 2018

AbstractObjectiveThe objective of this study was to identify the therapeutic effect and the underlying mechanism of glucagon‐like peptide 1 (GLP‐1) in the treatment of STZ‐induced diabetes mellitus (DM).MethodsMice were treated with STZ to establish an animal model of DM, which was further treated with a GLP‐1 receptor agonist. Subsequently, the status of glucose, insulin, nitric oxide, inflammatory and oxidative factors was evaluated and compared among Sham, STZ, and STZ + GLP‐1 groups. In addition, the intestinal flora spectrum in each group was also evaluated.ResultsIn this study, it was found that the administration of STZ increased the level of glucose and glycosylated hemoglobin but reduced the level of insulin. It was also found that the levels of inflammation and oxidative stress in STZ‐induced DM were both enhanced, as evidenced by a decreased level of catalase, superoxide dismutase, glutathione peroxidase, as well as increased levels of malonyldialdehyde, interleukin‐1β (IL‐1β), and IL‐6. Meanwhile, the expression of nitric oxide, a factor associated with both oxidative stress and inflammation, was also suppressed in STZ‐induced DM. More importantly, the imbalance of intestinal flora was observed in STZ‐induced DM, as shown by a decreased level of both total bacteria and that of some strains including Clostridium, Bacteroides, Lactobacilli, and Bifidobacteria.ConclusionIn summary, the findings of this study confirmed the antihyperglycemic effect of GLP‐1 and demonstrated that the therapeutic effect of GLP‐1 in the treatment of STZ‐induced DM was mediated, at least partially, by its ability to restore the balance of intestinal flora.
The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single‐nucleotide polymorphisms in rheumatoid arthritis patients
Authors: Zhang Tian‐Ping , Zhang Qin , Wu Jun , Zhao Yu‐Lan , Wang Jie‐Bing , Leng Rui‐Xue , Fan Yin‐Guang , Li Xiao‐Mei , Pan Hai‐Feng , Ye Dong‐Qing 
Published: August 2018

AbstractObjectivesThe aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single‐nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients.MethodsThe expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real‐time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP‐genotyping assays in 627 RA patients and 590 controls.ResultsThe lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C‐reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients.ConclusionsThe expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.
Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway
Authors: Wang Yan , Li Guoce , Zhao Li , Lv Jianping 
Published: August 2018

AbstractHOXA transcript at the distal tip (HOTTIP), which is a long noncoding RNA, plays an important role in multiple cancers and in coronary artery disease. Elevated microRNA‐143 (miR‐143) expression causes impaired glucose uptake that is responsible for the ischemic cerebral injury. However, the role and mechanism of HOTTIP in ischemic stroke are still unknown. The expression of HOTTIP and miR‐143 was first detected in mouse models of transient middle cerebral artery occlusion and in primary neurons exposed to oxygen‐glucose deprivation (OGD). We used gain‐of function and loss‐of function approaches in vitro to investigate the effect and mechanism of HOTTIP on ischemic stroke by evaluating cell viability, apoptosis, and glycolytic metabolism of neurons exposed to OGD. The HOTTIP expression was decreased, whereas miR‐143 increased in experimental ischemic stroke models. Overexpression of HOTTIP by the pcDNA3.1‐HOTTIP plasmid significantly increased cell viability, glucose uptake, and the expression of hexokinase 2 (HK‐2) and pyruvate kinase M2 that were reduced by OGD insult. The HOTTIP overexpression also diminished OGD induced the apoptosis and the caspase‐3 activity of neurons. The miR‐143 mimic reversed these effects, and anti‐miR‐143 enhanced them. In addition, we found that HOTTIP could function as a competing endogenous RNA for miR‐143 to modulate HK‐2 expression. In conclusion, the HOTTIP expression was reduced in ischemic stroke. The HOTTIP overexpression attenuated OGD‐induced neuronal injury and imbalanced glycolytic metabolism by sponging miR‐143, resulting in the de‐repression of its endogenous target HK‐2. Taken together, these findings improve understanding of the pathogenesis of ischemic stroke.
Crocin synergistically enhances the antiproliferative activity of 5‐flurouracil through Wnt/PI3K pathway in a mouse model of colitis‐associated colorectal cancer
Authors: Amerizadeh Forouzan , Rezaei Nastaran , Rahmani Farzad , Hassanian Seyed Mahdi , Moradi‐Marjaneh Reyhaneh , Fiuji Hamid , Boroumand Nadia , Nosrati‐Tirkani Abolfazl , Ghayour‐Mobarhan Majid , Ferns Gordon A. , Khazaei Majid , Avan Amir 
Published: August 2018

AbstractColorectal cancer (CRC) is the third most common cause of cancer‐related death, and hence there is a need for the identification of novel‐agents to improve the efficacy of existing therapies. There is growing evidence for the antitumor activity of crocin, although its activity and molecular mechanisms in CRC remains to be elucidated. Here we explored the therapeutic application of crocin or its combination with 5‐flurouracil in a mouse model of colitis‐associated colon cancer. The antiproliferative activity of crocin was assessed in two‐dimensional and three‐dimensional cell‐culture models. The migratory behaviors were determined, while the expression levels of several genes were assessed by quantitative reverse transcriptase polymerase chain reaction/Western blot analysis. We examined the anti‐inflammatory properties of crocin by pathological evaluation and disease‐activity index as well as oxidative or antioxidant markers: malondialdehyde (MDA) and total‐thiols (T‐SH) levels and superoxide dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell‐growth and the invasive behavior of CRC cells through modulation of the Wnt‐pathway and E‐cadherin. Moreover, administration of crocin alone, or in combination with 5‐FU dramatically reduced the tumor number and tumor size in both distal/mid‐colon followed by reduction in disease‐activity index. Crocin also suppressed the colonic inflammation induced by dextran‐sulfate‐sodium and notably recovered the increased levels of MDA, decreased thiol levels and activity of CAT levels. Crocin was able to ameliorate the severe inflammation with mucosal ulcers and high‐grade dysplastic crypts as detected by inflammation score, crypt loss, pathological changes and histology scores. We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high‐grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.
β‐Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats
Authors: Ames‐Sibin Ana P. , Barizão Camila L. , Castro‐Ghizoni Cristiane V. , Silva Francielli M. S. , Sá‐Nakanishi Anacharis B. , Bracht Lívia , Bersani‐Amado Ciomar A. , Marçal‐Natali Maria R. , Bracht Adelar , Comar Jurandir F. 
Published: August 2018

AbstractThe current study investigated the action of β‐caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant‐induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β‐caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg−1 β‐caryophyllene orally once a day during 18 days. Both doses of β‐caryophyllene reduced the adjuvant‐induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. β‐Caryophyllene, at the dose of 430 mg·kg
−1, abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil (
Copaifera reticulata) and, therefore, β‐caryophyllene is possibly responsible for the anti‐inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (−23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by β‐caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, β‐caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that β‐caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.
MicroRNA‐224 inhibition prevents progression of cervical carcinoma by targeting PTX3
Authors: Yu Li‐Mei , Wang Wei‐Wei , Qi Rong , Leng Tian‐Gang , Zhang Xiao‐Lu 
Published: August 2018

AbstractCervical carcinoma is known as one of the most lethal and common conditions in women worldwide. Increasing evidence shows that microRNAs (miRs) may be involved in the pathogenesis of cervical carcinoma. This study investigates the correlation between expression of miR‐224 in peripheral blood mononuclear cells and both diagnosis and prognosis of cervical carcinoma to clarify the effect miR‐224 has on the biological behaviors of the subjected cervical carcinoma cells. Initially, 132 patients diagnosed with cervical carcinoma and 120 healthy subjects were recruited. Peripheral blood expression of miR‐224 and PTX3 was detected. A telephone follow‐up was performed every 3 months after treatment. The diagnostic value of miR‐224 in cervical carcinoma was analyzed using the Receiver Operating Characteristic curve. The effects of both miR‐224 and PTX3 on cell proliferation, migration, and invasion were evaluated with an intervention of miR‐224 ectopic expression or depletion and PTX3 silencing. The bioinformatics prediction website and dual‐luciferase reporter assay revealed PTX3 to be a target gene for miR‐224. Moreover, miR‐224 was detected as over‐expressed, but PTX3 was under‐expressed in cervical carcinoma. Additionally, as a diagnostic biomarker, a high miR‐224 expression was closely linked with the progression of cervical carcinoma. Both miR‐224 overexpression and PTX3 silencing promoted cell proliferation, migration, and invasion, whereas, the aforementioned properties were depressed when miR‐224 was inhibited. Altogether, the miR‐224 overexpression may be a biological indicator in predicting the progression of cervical carcinoma. Thus, miR‐224 inhibition may significantly prevent cervical carcinoma progression by targeting the PTX3 gene.
Naked eye detection of the Mycobacterium tuberculosis complex by recombinase polymerase amplification—SYBR green I assays
Authors: Singpanomchai Nuntita , Akeda Yukihiro , Tomono Kazunori , Tamaru Aki , Santanirand Pitak , Ratthawongjirakul Panan 
Published: August 2018

AbstractBackgroundRapid diagnosis of Mycobacterium tuberculosis (Mtb) is key to controlling the spread of tuberculosis, which is a global health concern. In this study, isothermal recombinase polymerase amplification (RPA) was developed to detect specific targets of Mtb, IS6110 and IS1081. Additionally, SYBR Green I was used for endpoint detection of the RPA products by the naked eye.MethodA total of 146 genomic Mtb DNA samples and 24 genomic nontuberculous mycobacteria (NTM) DNA samples were amplified at IS6110 and IS1081 by RPA. After a complete amplification, the RPA amplicons were examined by agarose gel electrophoresis (RPA‐AGE) and SYBR Green I (RPA‐S) assays. The performance of the RPA assays was evaluated by comparing them to a conventional PCR.ResultsThe RPA assay demonstrated to have a good capability to differentiate Mtb from NTM with a very short turnaround time at a constant temperature. Compared to conventional PCR, the sensitivities and specificities of RPA‐AGE for IS6110 and IS1081 were 100%. The specificity of RPA‐S was 100% for both targets; however, its sensitivities for IS6110 and IS1081 were 97.95% and 99.32%, respectively. The limits of detection of IS6110 RPA‐AGE and RPA‐S were 0.05 and 0.5 ng, respectively, while the LODs of IS1081 RPA‐AGE and RPA‐S were 0.00005 and 0.05 ng, respectively. Both RPA assays showed a satisfying diagnostic specificity, with no cross‐reaction with other bacteria.ConclusionA rapid, sensitive, naked eye RPA assay can be integrated into point‐of‐care diagnosis for Mtb detection, especially in remote areas where laboratory instrument resources are limited.