bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insertion/deletion polymorphism in the 3′ untranslated region of COL1A2 disrupts its interaction with microRNA‐382 and leads to decreased susceptibility to osteoporotic fracture
Authors: Chen Ziqi , Wu Yanping , Kong Jianjun , Li Yan , Wang Hongbin , Zhao Hongbin , Wu Zhanyong 
Published: March 2019

AbstractA growing body of evidence has proved that the expression of COL1A2 is associated with a reduced risk of osteoporotic fracture. One single‐nucleotide polymorphism (rs3917) located within the 3′‐untranslated region of COL1A2 may “alter” binding site of miR‐382 and thereby associated with the risk of osteoporotic fracture. Bioinformatic analysis, luciferase reporter assay, site‐directed mutagenesis, Western blot and real‐time PCR were performed in this study. In this study, we validated COL1A2 as a target of miR‐382 in osteoblast. In addition, bone tissue samples were genotyped as wild‐type rs3917, heterozygous rs3917, and homozygous rs3917. The expression of miR‐382 was comparable between the genotype groups, whereas the expression of COL1A2 mRNA and protein was much higher in heterozygous rs3917 and homozygous rs3917 than the wild‐type rs3917 group. Furthermore, we transfected the wild‐type rs3917 and heterozygous rs3917 cells with miR‐382 mimics or inhibitors and found that the transfection with miR‐382 mimics significantly increased the level of the miR‐382 in the cells of both genotypes, and the introduction of miR‐382 inhibitors substantially suppressed the level of miR‐382 in both cells. In wild‐type rs3917 cells, transfection of miR‐382 mimics and COL1A2 small interfering RNA (siRNA) similarly and substantially downregulated the expression of COL1A2, while in heterozygous rs3917 cells, only COL1A2 siRNA notably reduced the expression of COL1A2, whereas introduction of miR‐382 mimics left expression of COL1A2 intact. The findings showed rs3917 polymorphism interfered with the interaction between COL1A2 mRNA and miR‐382, and minor allele is associated with a reduced risk of osteoporotic fracture.
TET1 suppresses colon cancer proliferation by impairing β‐catenin signal pathway
Authors: Guo Hailong , Zhu Hongyi , Zhang Jie , Wan Boshun , Shen Zhiyong 
Published: March 2019

AbstractThe function of ten‐eleven translocation methylcytosine dioxygenase 1 (TET1) in cancer is background dependent and may be involved in the initial step of active DNA demethylation, while there is little research to decipher the role of TET1 in DNA methylation‐sensitive colon cancer. Downregulated TET1 expression assayed by quantitative real‐time PCR (qRT‐PCR) was observed in both colon cancer samples and cancer cell lines of HT29, HCT116, and SW48. Such downregulation could promote colon cancer cells proliferation as indicated by the fact that shTET1 could increase the viability of HT29 and HCT116 cells determined by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide and cell count assay accompanied with upregulation of β‐catenin (CTNNB1) and WNT luciferase activity, which was further confirmed as shTET1 could increase the tumor volume and tumor weight, and decrease the body weight in HT29 cells inoculated BALB/C nude mice. The CTNNB1 transfection could rescue the cell growth diminished by normal expression of TET1. shTET1 could promote axis inhibition protein1 (AXIN1) expression and the cell proliferation effect induced by TET1 short hairpin RNA was attenuated by co‐inhibition of AXIN1. All of these indicate that TET1 can suppress colon cancer proliferation and the inhibition of the β‐catenin pathway is AXIN1 dependent.
SPOCK1 contributes to the third‐generation EGFR tyrosine kinase inhibitors resistance in lung cancer
Authors: Gao Yujuan , Yu Min , Ma Miao , Zhuang Yi , Qiu Xiaohua , Zhao Qi , Dai Jinghong , Cai Hourong , Yan Xin 
Published: March 2019

AbstractIntroductionExplanation of the mechanism of resistance to third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and the development of a novel strategy for drug resistance are imperative in third‐generation EGFR‐TKIs‐resistant non‐small cell lung cancer (NSCLC). SPOCK1 was found to be abnormally expressed in various tumors including lung cancer, however, there was no study focused on the role of SPOCK1 in third‐generation EGFR‐TKIs resistant lung cancer cells.Methods and ResultsWe investigated the roles of SPOCK1 in NSCLC with third‐generation EGFR‐TKIs resistance. We showed that SPOCK1 was upregulated in the osimertinib‐resistant lung cancer cells and knockdown of SPOCK1 inhibits osimertinib‐resistant cells growth and overcomes resistance. Furthermore, we demonstrated that the SPOCK1 was higher in clinical NSCLC specimens compared with the normal lung tissues, and the higher expression of SPOCK1 correlated with poor prognosis. In addition, the overexpression of SPOCK1 in NSCLC tissues was positively correlated with MMP11 and TGFβ1.ConclusionOur study suggested that SPOCK1 could be an independent prognostic factor in NSCLC and would be a candidate for target therapy in osimertinib‐resistant lung tumors.
Activation of PERK in ET‐1‐ and thrombin‐induced pulmonary fibroblast differentiation: Inhibitory effects of curcumin
Authors: Chen Yen‐Chou , Chen Bing‐Chang , Huang Huei‐Mei , Lin Shin‐Hua , Lin Chien‐Huang 
Published: March 2019

AbstractIn the present study, we investigated the role of PKR‐like endoplasmic reticular kinase (PERK), an endoplasmic reticulum (ER) stress kinase, in endothelin 1 (ET‐1)‐ and thrombin‐induced pulmonary fibrosis (PF), and the preventive effects of curcumin (CUR). Using the human embryonic WI‐38 lung fibroblast cell line, ET‐1 and thrombin induced the expression of ER stress‐related proteins (CCAAT‐enhancer‐binding protein homologous protein, PERK, and binding immunoglobulin protein), a profibrogenic factor (cellular communication network factor 2 [CCN2]), and differentiation markers including α‐smooth muscle actin (α‐SMA), collagen I (Col I), and Col IV. Knockdown of PERK expression via small interfering RNA (siRNA) significantly reduced the increases in CCN2, α‐SMA, Col I, and Col IV proteins in WI‐38 cells according to western blot analysis and immunohistochemistry (IHC). Activation of c‐Jun N‐terminal kinase (JNK) was observed in ET‐1‐ and thrombin‐treated WI‐38 cells, and the addition of a JNK inhibitor (SP) suppressed the induction of the indicated proteins by ET‐1 and thrombin. Thapsigargin (TG), an ER stress inducer, elevated expressions of PERK and ER stress‐related proteins with increased differentiation of WI‐38 cells. Knockdown of PERK by siRNA or the PERK inhibitor glycogen synthesis kinase reduced expressions of the differentiation markers, α‐SMA and Col IV, in WI‐38 cells. CUR concentration‐dependently inhibited ET‐1‐ or thrombin‐induced CCN2, α‐SMA, and vimentin proteins with decreased levels of phosphorylated mitogen‐activated protein kinase and PERK in WI‐38 cells. An in vivo bleomycin‐induced PF study showed that an intraperitoneal injection of CUR (30 mg/kg) reduced expressions of α‐SMA, CCN2, Col IV, and vimentin in lung tissues via IHC staining using specific antibodies. This study is the first to demonstrate that PERK activation contributes to pulmonary fibroblast differentiation elicited by ET‐1 or thrombin, and the inhibitory activity of CUR against PF is demonstrated herein.
HMGA2 and Bach‐1 cooperate to promote breast cancer cell malignancy
Authors: Mansoori Behzad , Mohammadi Ali , Asadzadeh Zahra , Shirjang Solmaz , Minouei Mahsa , Abedi Gaballu Fereydoon , Shajari Neda , Kazemi Tohid , Gjerstorff Morten F. , Duijf Pascal H.G. , Baradaran Behzad 
Published: March 2019

AbstractDuring breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach‐1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach‐1 promote cancer development has been limited. We found that HMGA2 and Bach‐1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach‐1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach‐1 knockdown additively decrease cell proliferation, migration, epithelial‐to‐mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase‐3 and caspase‐9. First the first time, we show that HMGA2 and Bach‐1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer.
Junctophilins emerge as novel therapeutic targets
Authors: Jiang Jinyong , Tang Mingzhu , Huang Zhen , Chen Linxi 
Published: March 2019

AbstractJunctophilins (JPs) emerge to play key role in human pathophysiology. This family includes four subtypes (JP1–4), which are differentially detected in excitable cells. Previous work demonstrated the knockout of JPs that seriously damage physiological functions in skeletal muscle, cardiac, and neurons. Here, we summarize latest papers on the essential function of JPs in some Ca2+‐related diseases and neurological diseases, such as primary muscle disease, cardiomyopathies, Type 2 diabetes, gastrointestinal cancer, Huntington’s disease‐like 2, and Charcot‐Marie‐Tooth disease. Growing evidence suggests that targeting JPs might be a promising therapeutic approach to achieve better clinical efficacy in Ca
2+‐related diseases and neurological diseases.
Metabolic effects of antidiabetic drugs on adipocytes and adipokine expression
Authors: Yaribeygi Habib , Simental‐Mendía Luis E. , Barreto George E. , Sahebkar Amirhossein 
Published: March 2019

AbstractSeveral classes of antidiabetic agents have been developed that achieve their hypoglycemic outcomes via various molecular mechanisms. Adipose tissue is a major metabolic and energy‐storing tissue and plays an important role in many metabolic pathways, including insulin signaling and insulin sensitivity. Adipose tissue monitors and regulates whole body homeostasis via production and release of potent proteins, such as adipokine and adiponectin, into the circulation. Therefore, any agent that can modulate adipocyte metabolism can, in turn, affect metabolic and glucose homeostatic pathways. Antidiabetic drugs are not only recognized primarily as hypoglycemic agents but may also alter adipose tissue itself, as well as adipocyte‐derived adipokine expression and secretion. In the current review, we present the major evidence concerning routinely used antidiabetic agents on adipocyte metabolism and adipokine expression.
Altered gene expression of hydrogen sulfide‐producing enzymes in the liver and muscles tissues of hyperthyroid rats
Authors: Jeddi Sajad , Gholami Hanieh , Gheibi Sevda , Kashfi Khosrow , Ghasemi Asghar 
Published: March 2019

AbstractThyroid hormones have a role in the regulation of hydrogen sulfide (H2S) biosynthesis. In this study, we determined the effects of hyperthyroidism on H2S levels in various tissues and messenger RNA (mRNA) expression of cystathionine‐β‐synthase (CBS), cystathionine‐γ‐lyase (CSE), and 3‐mercaptopyruvate sulfurtransferase (3‐MST) in the liver and muscles of the rat. Sixteen male Wistar rats were divided into the hyperthyroid and the control groups. Hyperthyroidism was induced by adding l‐thyroxine (12 mg/L) to drinking water for a period of 21 days. H2S concentrations in serum, liver, aorta, heart, and soleus muscles, as well as mRNA expressions of CBS, CSE, and 3‐MST in these tissues were measured at Day 21. Hyperthyroid rats had lower H2S levels in the serum compared with controls (14.7 ± 1.4 vs. 25.7 ± 1.6 µmol/L, p < 0.001). Compared with controls, hyperthyroid rats had lower levels of H2S in the aorta (89%), heart (80%), and soleus (103%) muscles, but higher levels in the liver (35%). Hyperthyroidism decreased the ratio of CBS/CSE mRNA expression in the liver and the CSE/CBS mRNA expression in the muscles by decreasing CBS levels in liver (34% cf. controls) and CSE levels in the aorta, heart, and soleus muscles (respectively, 51%, 7%, and 52% cf.). In addition, hyperthyroidism decreased the mRNA expression of 3‐MST in the liver (51%) and aorta (33%), and increased it in the heart (300%) and soleus muscle (182%). In conclusion, hyperthyroidism increased H2S levels in the liver and decreased it in muscles; these effects are at least in part due to increases and decreases in expression of CSE in the liver and muscles, respectively. These data indicate an association between thyroid hormone status and gene expression of the H2S‐producing enzymes in the rat.
High cholesterol inhibits tendon‐related gene expressions in tendon‐derived stem cells through reactive oxygen species‐activated nuclear factor‐κB signaling
Authors: Li Kaiqun , Deng Ganming , Deng Ye , Chen Siwei , Wu Hangtian , Cheng Caiyu , Zhang Xianrong , Yu Bin , Zhang Kairui 
Published: March 2019

AbstractClinical studies have indicated that increased serum cholesterol levels raised the risk of tendinopathy in hypercholesterolemia, but the effect of cholesterol on tendon‐derived stem cells (TDSCs) and its underlying mechanism have not been studied. The purpose of this study is to investigate the association between cholesterol and tendinopathy in vitro and in vivo, and its underlying molecular mechanism as well. In TDSCs, the effect of cholesterol was assessed by quantitative polymerase chain reaction, western blot analysis, and immunofluorescence staining. Intracellular levels of reactive oxygen species (ROS) was detected, using flow cytometry. The link between nuclear factor (NF)‐κB signaling and the effect of cholesterol was evaluated using a representative IκB kinase (IKK) inhibitor, BAY 11‐7082. In addition, Achilles tendons from apolipoprotein E mice fed with a high‐fat diet were histologically assessed using hematoxylin and eosin staining and immunohistochemistry. We found that high cholesterol apparently lowered the expression of tendon cell markers (collagen 1, scleraxis, tenomodulin), and elevated ROS levels via the NF‐κB pathway both in vitro and in vivo. The ROS scavenger N‐acetylcysteine (NAC) and BAY 11‐7082 reversed the inhibiting effect of cholesterol on the tendon‐related gene expressions of TDSCs. Moreover, NAC blocked cholesterol‐induced phosphorylation of IκBα and p65. Significant histological alternation in vivo was shown in Achilles tendon in the hypercholesterolemic group. These results indicated that high cholesterol may inhibit the tendon‐related gene expressions in TDSCs via ROS‐activated NF‐кB signaling, implying pathogenesis of tendinopathy in hypercholesterolemia and suggesting a new mechanism underlying hypercholesterolemia‐induced tendinopathy.
Clinical models of telehealth in genetics: A regional telegenetics landscape
Authors: Terry Alissa B. , Wylie Amanda , Raspa Melissa , Vogel Beth , Sanghavi Kunal , Djurdjinovic Luba , Caggana Michele , Bodurtha Joann 
Published: March 2019

AbstractThe use of live video consultations in genetics has been shown to improve patient access with high satisfaction; however, little is known about the current landscape of clinical telehealth models in the field of genetics (i.e., telegenetics). This survey aimed to address that gap across seven states and the District of Columbia. Among 51 self‐defined telegenetics programs responding to an online survey, 32 currently utilized live videoconferencing as at least one of their technologies (i.e., were “video‐capable”). Analysis of this subgroup revealed that medical institutions were the most common program setting, and prenatal and cancer services were the most common sub‐specialty. Forty‐seven percent of these programs reported billing insurance for patient care. When exploring measures of patient access among these programs, 56% had a wait time of under 2 weeks, 25% saw more than 50 patients per month, 50% estimated their geographic reach at over 200 miles, and 59% were able to provide remote telegenetics consultations to patients’ homes. Professional licensure was reported as the biggest barrier, and patient access and convenience were reported as the largest benefit and success. Among the 19 remaining programs, eight currently active programs exclusively used telephone technology; these were less likely to have a geneticist (p = 0.01), had a shorter wait time (p = 0.04), and had been established for a longer time (p = 0.02) when compared to video‐capable programs. Further, two currently active programs indicated the use of store‐and‐forward telehealth. Finally, nine programs were currently planning their programs, with a focus on video‐capable technologies and more varied patient specialties. We observed a diverse landscape of telehealth models being utilized to provide genetic services, and the data demonstrated that these programs are focused on enhancing patient access. Our query about telegenetics drew responses from programs that were not using live videoconferencing technology models, which prompts further exploration, and challenges us to develop consensus around the meaning of “telegenetics.” Similarly, our data suggest a need for continued research to assess the equivalency, accessibility, and role of telephone consultations across genetic services. While a multitude of policy factors influence which service delivery models are utilized, further research on these varied approaches, and their associated patient outcomes, is also needed to inform program development.
Genetic counselor workforce generational diversity: Millennials to Baby Boomers
Authors: Reiser Catherine , Van Vreede Victoria , Petty Elizabeth M. 
Published: March 2019

AbstractThere are currently three generations of individuals that make up the genetic counselor workforce: Baby‐Boomers, Generation X, and Millennials. These generations are presumed to be shaped by the historical, cultural, and social events that occurred during critical developmental periods. Understanding the underlying perceptions and viewpoints of genetic counselors regarding the multigenerational workforce may facilitate successful working relationships as well as recognition of the perceived unique characteristics that each generation offers. An online survey was distributed to practicing genetics counselors (GC) and genetic counseling students through the National Society of Genetic Counselors and the American Board of Genetic Counseling to elicit opinions about the perceived characteristics or skills of genetic counselors in each generation. Respondents (n = 407, estimated 10% response) preferentially assigned certain traits or skills to specific generations including their own. Findings suggest GC Baby Boomers were least likely to be described as “comfortable with phone or skype counseling” (p < 0.0001), Millennial GC, were least often assigned the term “Strong respect for authority” (p < 0.0005) and Generation X GC were most likely to be described as “Does not ask for feedback” (p < 0.05). These research findings demonstrate that GC perceive that their colleagues from every generation have unique attributes to bring to the profession and these attributes match those typically described in the U.S. literature about non‐GC cohorts.
The edge‐subgraph poset of a graph and the edge reconstruction conjecture
Authors: Thatte Bhalchandra D. 
Published: March 2019

AbstractWe consider only finite simple graphs in this paper. Earlier we showed that many invariants of a graph can be computed from the isomorphism class of its partially ordered set of distinct unlabeled non‐empty induced subgraphs, that is, the subgraphs themselves are not required. In this paper, we consider an analogous problem of reconstructing an arbitrary graph up to isomorphism from its abstract edge‐subgraph poset , which we call the ‐reconstruction problem. We present an infinite family of graphs that are not ‐reconstructible and show that the edge reconstruction conjecture is true if and only if the graphs in the family are the only graphs that are not ‐reconstructible. Let be the set of all unlabeled graphs. Let denote the number of homomorphisms from to . Let be a bijection such that for all , we have . We conjecture that is the identity map. Our conjecture is motivated by the homomorphism cancellation results of Lovász. We prove that the conjecture stated above is weaker than the edge reconstruction conjecture.
Surgical and histological boundary of the hepatic hilar plate system: basic study relevant to surgery for hilar cholangiocarcinoma regarding the “true” proximal ductal margin
Authors: Kikuchi Yutaro , Matuyama Ryusei , Hiroshima Yukihiko , Murakami Takashi , Bouvet Michael , Morioka Daisuke , Hoffman Robert M. , Endo Itaru 
Published: March 2019

AbstractBackgroundWe sought to expand the clinico‐anatomical limit of the proximal ductal margin (Limit‐PDM) for resectability of hilar cholangiocarcinoma (HCCA).MethodsThe practical boundary of the hilar plate (PBHP) was defined as the location where the bile duct (BD) could not be isolated by dissection. The distance between PBHP and two well‐known clinical landmarks of Limit‐PDM, the right edge of the bifurcation of the anterior and posterior branch of the right portal vein (Posterior‐Landmark) and the left edge of the umbilical portion of the portal vein (Left‐Landmark), and histological features around the PBHP were assessed using 55 adult cadaver livers.ResultsBD was almost always isolatable beyond the traditional clinical landmarks. The median distance was 6.9 mm (interquartile range [IQR] 6.0–8.3 mm) between the PBHP and the Posterior‐Landmark, and 8.9 mm (IQR 6.7–10.2 mm) between the PBHP and the Left‐Landmark. Histologically, the sheath surrounding the portal triad was loose, thick with few elastic fibers and small arteries near the hepatic hilum. Near the PBHP, the sheath was dense, thin, and abundant with elastic fibers and small arteries.ConclusionsLimit‐PDM is more peripheral than the traditional clinical landmark‐based margin and histological transition near the PBHP was revealed.