bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: Long noncoding RNA HOTAIR knockdown inhibits autophagy and epithelial–mesenchymal transition through the Wnt signaling pathway in radioresistant human cervical cancer HeLa cells
Authors: Guo Xinggang , Xiao Hongqi , Guo Sihong , Li Jing , Wang Yuxia , Chen Jie , Lou Ge 
Published: October 2018

AbstractCervical cancer is one of the most common female malignancies around the world, and radiation resistance is a major obstacle to cancer therapy. Previously, overexpression of the long noncoding ribonucleic acid (RNA) (lncRNA) HOX transcript antisense RNA (HOTAIR) has been found to be associated with the invasion and metastasis capacities of several epithelial cancers, including cervical cancer. To gain insights into the molecular mechanisms of HOTAIR in cervical cancer resistance to radiotherapy, we investigated cellular autophagy and epithelial‐to‐mesenchymal transition (EMT) in radioresistant human cervical cancer HeLa cells when HOTAIR was suppressed. HOTAIR levels were quantified in cancerous and noncancerous cervical tissues obtained from 108 patients with cervical cancer. Next, we inhibited HOTAIR by RNA interference and activated the Wnt signaling pathway by LiCl in radioresistant HeLa cells to investigate the regulatory mechanisms for the HOTAIR mediating Wnt signaling pathway. We determined that the upregulated HOTAIR may contribute to cervical cancer progression. We found that the short interfering ribonucleic acid (siRNA)‐mediated knockdown of HOTAIR disturbed the Wnt signaling pathway, reduced autophagy, inhibited EMT, decreased cell proliferation, and induced apoptosis in radioresistant HeLa cells. It is worthy to note that the combination treatment of siRNA‐HOTAIR and LiCl demonstrated that the activation of the Wnt signaling pathway is responsible for the beneficial effect of HOTAIR knockdown in enhancing sensitivity to radiotherapy in radioresistant HeLa cells. Together, our results revealed an important role of HOTAIR in regulating cervical cancer resistance to radiotherapy. Functional suppression of HOTAIR could enhance sensitivity to radiotherapy by reduction of autophagy and reversal of EMT through the suppression of the Wnt signaling pathway.
Tet methylcytosine dioxygenase 1 promotes hypoxic gene induction and cell migration in colon cancer
Authors: Ma Ling , Qi Tianyang , Wang Shensen , Hao Miao , Sakhawat Ali , Liang Tianya , Zhang Lin , Cong Xianling , Huang Yinghui 
Published: October 2018

AbstractTen‐eleven translocation 1 (TET1), a widely reported DNA demethylation protein, has been associated with tumorigenesis and metastasis. However, whether TET1 is an oncogene or tumor suppressor gene has been controversial; the mechanism of how TET1 affects cancer progression remains unclear. The current study aims to investigate how TET1 is changed in the tumor microenvironment and to explore the mechanisms of how TET1 affects colon cancer progression. Because hypoxia prevails on solid tumors, we established an important connection between hypoxia and DNA demethylation in tumorigenesis. By qPCR and RNA interference (RNAi) technology, we found that hypoxia increased TET1 expression with a hypoxia‐inducible factor‐1‐alpha (HIF‐1α)‐dependent manner. By CHIP‐qPCR and pyrosequencing technology, we demonstrated that TET1 regulated the target gene expression of HIF‐1α through HIF‐1α binding to hypoxia‐responsive elements (HREs), and HIF‐1α binding to HREs depended on CpG methylation levels. By Cell Counting Kit‐8 (CCK‐8) and transwell assay, we showed that loss of TET1 did not affect cell proliferation but inhibited migration. We also identified two novel gene mutants of TET1 in 120 paired tumor/normal tissue specimens by DNA sequencing and found that TET1 E2082K mutant blocked the TET1‐enhanced cell migration. Our results showed that the downregulation of TET1 rescued the abnormally high levels of gene expression resulting from hypoxia in tumors and reduced the migration activity of tumor cells, suggesting a therapeutic role by interference with TET1 in colon cancer treatment. By demonstrating that hypoxia upregulated TET1 and that TET1 drove HIF‐1α‐responsive genes, we showed that an epigenetic mechanism and tumor microenvironment‐driven models coexisted and mutually affected colon cancer.
HOTAIR promotes osteosarcoma development by sponging miR‐217 and targeting ZEB1
Authors: Wang Bing , Qu Xing‐Long , Liu Jiaxiang , Lu Junhui , Zhou Zong‐Yu 
Published: October 2018

AbstractLong noncoding RNAs (lncRNAs) have drawn increasing attention because of the role which they play in various diseases, including osteosarcoma. So far, the function and mechanism of HOTAIR in osteosarcoma are unclear. In our study, we observed that HOTAIR was elevated accompanied with a decrease of miR‐217 and an increase of ZEB1 in human osteosarcoma cells including U2OS, MG63, Saos‐2, and SW1353 compared with human osteoblast cell line hFOB. In addition, the subsequent functional assay exhibited that silencing HOTAIR could significantly repress osteosarcoma cell growth, migration, invasion, and induce cell apoptosis capacity, which indicated that HOTAIR exerted an oncogenic role in osteosarcoma. Moreover, it was revealed by using bioinformatics analysis that HOTAIR can be targeted by microRNA‐217 (miR‐217). miR‐217 has been recognized as a crucial tumor suppressive gene in cancers. We verified that mimics of miR‐217 were able to suppress the osteosarcoma development. Furthermore, real‐time quantitative PCR showed that HOTAIR siRNA increased miR‐217 expression. Besides these, ZEB1 was identified as a downstream gene of miR‐217 and we found that HOTAIR can mediate osteosarcoma progress by upregulating ZEB1 expression via acting as a competitive endogenous RNA (ceRNA) via miR‐217. Taken these together, our findings in this study indicated that HOTAIR/miR‐217/ZEB1 axis, as a novel research point can provide new insights into molecular mechanism of osteosarcoma development.
LINC00961 restrains cancer progression via modulating epithelial–mesenchymal transition in renal cell carcinoma
Authors: Chen Dongming , Zhu Meng , Su Huang , Chen Jiexun , Xu Xianlin , Cao Changchun 
Published: October 2018

AbstractRecently, long noncoding RNA have been identified as new gene regulators and prognostic biomarkers in various cancers, including renal cell carcinoma (RCC). The expression and biological roles of LINC00961 have been reported in many human cancers. However, up to date, no study of LINC00961 has been shown in RCC. Currently, we aimed to investigate the function of LINC00961 in RCC progression. Interestingly, we observed that LINC00961 could act as a novel biomarker in predicting the diagnosis of RCC. Then, we found that LINC00961 was greatly downregulated in RCC cell lines (Caki‐1, Caki‐2, 786‐O, A498, and ACHN cells) compared with normal renal cell lines (HK‐2 cells). Then, 786‐O cells and ACHN cells were infected with LV‐LINC00961. As displayed in our current study, LINC00961 overexpression could obviously suppress the proliferation and survival of RCC cells in vitro. In addition, RCC cell apoptosis was greatly induced and cell cycle progression was blocked in G1 phase by upregulation of LINC00961 in 786‐O cells and ACHN cells. Subsequently, we found that LV‐LINC00961 was able to restrain RCC cell migration and cell invasion capacity. Meanwhile, the messenger RNA and protein expression levels of epithelial–mesenchymal transition (EMT)‐associated markers Slug and N‐cadherin in RCC cell lines were dramatically inhibited by overexpressing LINC00961. Finally, the in vivo experiment was carried out and we observed that LINC00961 could inhibit RCC development through modulating EMT process. Taken these together, it was indicated in our study that LINC00961 was involved in RCC progression through targeting EMT pathway.
Narrative review of the effects of antidiabetic drugs on albuminuria
Authors: Yaribeygi Habib , Atkin Stephen L. , Katsiki Niki , Sahebkar Amirhossein 
Published: October 2018

AbstractDiabetes mellitus is the most prevalent metabolic disorder worldwide. Glycemic control is the main focus of antidiabetic therapy. However, there are data suggesting that some antidiabetic drugs may have intrinsic beneficial renal effects and protect against the development and progression of albuminuria, thus minimizing the risk of diabetic nephropathy. These pharmacological agents can suppress upstream molecular pathways involved in the pathophysiology of diabetes‐induced renal dysfunction such as oxidative stress, inflammatory responses, and apoptosis. In this narrative review, the pathophysiology of albuminuria in patients with diabetic nephropathy is discussed. Furthermore, the renoprotective effects of antidiabetic drugs, focusing on albuminuria, are reviewed.
Inhibition of the formation of autophagosome but not autolysosome augments ABT‐751‐induced apoptosis in TP53‐deficient Hep‐3B cells
Authors: Wei Ren‐Jie , Wu Wen‐Ren , Pan Cheng‐Tang , Yu Chun‐Yen , Li Chien‐Feng , Chen Lih‐Ren , Liang Shih‐Shin , Shiue Yow‐Ling 
Published: October 2018

AbstarctThe objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel antimicrotubule drug, ABT‐751, in a tumor protein p53 (
TP53)‐deficient hepatocellular carcinoma‐derived Hep‐3B cells. A series of in vitro assays indicated that ABT‐751 caused the disruption of the mitotic spindle structure, collapse of mitochondrial membrane potential, generation of reactive oxygen species, DNA damage, G
2/M cell cycle arrest, inhibition of anchorage‐independent cell growth and apoptosis in Hep‐3B cells accompanied by alteration of the expression levels of several DNA damage checkpoint proteins and cell cycle regulators. Subsequently, ABT‐751 triggered apoptosis along with markedly upregulated several proapoptotic proteins involving in extrinsic, intrinsic, and caspase‐mediated apoptotic pathways. A pan‐caspase inhibitor suppressed ABT‐751‐induced apoptosis. ABT‐751 also induced autophagy soon after the occurrence of apoptosis through the suppression of AKT serine/threonine kinase/mechanistic target of rapamycin signaling pathway. Exogenous expression of the
TP53 gene significantly incurred both apoptosis and autophagy in Hep‐3B cells. Pharmacological inhibition of autophagosome (early autophagy) but not autolysosome (late autophagy) enhanced ABT‐751‐induced apoptosis in
TP53‐deficient Hep‐3B cells. Our study provided a new strategy to augment ABT‐751‐induced apoptosis in
TP53‐deficient cells.
The C‐terminal flanking peptide of neuropeptide Y (NPY) is not essential for seizure‐suppressant actions of prepro‐NPY overexpression in male rats
Authors: Soud Katia , Jørgensen Søren Heide , Woldbye David Paul Drucker , Sørensen Andreas Toft 
Published: October 2018

AbstractThe full coding sequence of neuropeptide Y (NPY), prepro‐NPY, is sequentially metabolized into three peptides; an N‐terminus 28‐amino acid signaling peptide, the NPY peptide itself (NPY1‐36), and a 30‐amino acid C‐terminus peptide, known as the C‐terminal flanking peptide of neuropeptide‐Y (CPON). While the signaling peptide directs intracellular trafficking and NPY1‐36 is well characterized, the biological function of CPON is unknown. This is noteworthy because CPON is co‐stored and co‐released along with NPY1‐36 and could thus potentially serve important functions. To assess the role of CPON, we adapted a viral genetic approach using two different vector designs encoding NPY, but where the CPON coding sequence was excluded from one of the vectors. Thus, the effect of CPON was indirectly assessed. Male rats received intrahippocampal injections of either a vector encoding NPY1‐39 whose metabolism yields NPY1‐36 and not CPON, or a prepro‐NPY vector encoding both NPY1‐36 and CPON. A third vector encoding EGFP served as control. We subsequently studied to what extent CPON might affect seizure susceptibility and memory performance, respectively, to address two important questions to evaluate the potential of NPY gene therapy in epilepsy. Both NPY vectors, as compared to EGFP control, were found to be equally effective at suppressing acute kainate–induced seizures, and both did not influence learning and memory performance in the Morris water maze. Thus CPON itself does not appear to aid actions governed by vector–mediated overexpression of NPY1‐36 within the hippocampus. Whether CPON serves other important functions remains to be determined.
Histological and histomorphometric evaluation of hydroxyapatite‐based biomaterials in surgically created defects around implants in dogs
Authors: Attia Mai S. , Mohammed Hend M. , Attia Mohammed G. , Hamid Mohamed A. Abd El , Shoeriabah Eatemad A. 
Published: October 2018

AbstractBackgroundThe present study evaluated histologically and histometrically the efficacy of micro‐, nano‐, or mixed‐composite of hydroxyapatite (HA) graft in treatment of surgically created defects around dental implants in mongrel dogs.MethodsImmediate implant was used after extraction of the lower third premolar in mongrel male dogs. Critical‐size defects were created in intact proximal alveolar bone to each implant. The defects were divided randomly into four groups of two animals based on biomaterials used for treatment: 1) received no treatment (negative control); 2) defects treated with nano‐HA bone graft; 3) defects treated with micro‐HA bone graft; and 4) defects treated with a mixed composite of micro‐HA and nano‐HA. Animals were sacrificed at 2 months and histologic and histometric evaluation was performed.ResultsThe amount of new bone formed with nano‐HA bone graft was highly more significant than that obtained by a micro‐ or mixed‐composite of hydroxyapatite. Defects treated by mixed hydroxyapatite showed the greatest value in mean area percentage of collagen fibers using Masson trichrome stain.ConclusionsThe present study demonstrated that nano‐hydroxyapatite bone graft was better than micro‐HA or mixed‐HA bone graft in new bone formation in standardized surgically created defects around dental implants. However, longer period is necessary to determine the time taken for complete resorption of bone graft materials and their replacement with new bone.
Effects of methods of hydration of a biphasic ceramic graft on bone regeneration of extraction socket defects
Authors: Santos Igor Guimarães Barros Paulinelli , de Santana Carolina Miler Mattos , Alves Adriana Therezinha Neves Novelino , de Uzeda Marcelo José Pinheiro Gueded , Calasans‐Maia Mônica Diuana , de Santana Ronaldo Barcellos 
Published: October 2018

AbstractBackgroundAlveolar volumetric changes are inherent to the healing process after tooth extraction and filling of the extraction site with biomaterials can reduce these volumetric changes and provide a more favorable environment for the future prosthetic restoration with implants. Among the biomaterials available, biphasic ceramic compounds have shown promissing clinical results, however, histologic evaluation of bone tissue response to different hydration and incorporation methods are limited. The objective of this study was to comparatively evaluatein vivothe osteoconductive potential of the biphasic ceramic bone substitute (SBC) composed of beta‐tricalcium phosphate and hydroxyapatite after different hydration methodologies in rat extraction sockets.MethodsWistar rats (n = 20) were randomly distributed in two subgroups (G1, G2) according to the hydration methods used. After extraction of the right upper central incisor the alveoli were filled with SBC hydrated by two different methods. Group 1: biomaterial hydrated in blood; Group 2: biomaterial hydrated in physiologic saline. The animals were euthanized after 1 and 6 weeks for removal of the bone blocks containing the biomaterial and were submitted to histologic processing. Five‐μm‐thick demineralized sections of the samples were stained with hematoxylin and eosin (HE) and subjected to histomorphometric analysis.ResultsBone formation was limited 7 days after the extraction procedure and increased in both groups between 7 and 42 days from surgery, demonstrating a time dependent increase of bone volume throughtout the experimental period (p < 0.05).ConclusionsThe hydration of SBC with saline significantly increased new bone formation and reduced connective tissue volume after 42 days demonstrating that hydration method may significantly influence bone healing in such defects, and, thus should be carefully performed.
Assessing the consistency assumptions underlying network meta‐regression using aggregate data
Authors: Donegan Sarah , Dias Sofia , Welton Nicky J. 
Published: October 2018

When numerous treatments exist for a disease (Treatments 1, 2, 3, etc), network meta‐regression (NMR) examines whether each relative treatment effect (eg, mean difference for 2 vs 1, 3 vs 1, and 3 vs 2) differs according to a covariate (eg, disease severity). Two consistency assumptions underlie NMR: consistency of the treatment effects at the covariate value 0 and consistency of the regression coefficients for the treatment by covariate interaction. The NMR results may be unreliable when the assumptions do not hold. Furthermore, interactions may exist but are not found because inconsistency of the coefficients is masking them, for example, when the treatment effect increases as the covariate increases using direct evidence but the effect decreases with the increasing covariate using indirect evidence.We outline existing NMR models that incorporate different types of treatment by covariate interaction. We then introduce models that can be used to assess the consistency assumptions underlying NMR for aggregate data. We extend existing node‐splitting models, the unrelated mean effects inconsistency model, and the design by treatment inconsistency model to incorporate covariate interactions. We propose models for assessing both consistency assumptions simultaneously and models for assessing each of the assumptions in turn to gain a more thorough understanding of consistency.We apply the methods in a Bayesian framework to trial‐level data comparing antimalarial treatments using the covariate average age and to four fabricated data sets to demonstrate key scenarios.We discuss the pros and cons of the methods and important considerations when applying models to aggregated data.
Predictive factors for adrenal metastasis in extra‐adrenal malignancy patients with solitary adrenal mass
Authors: Byeon Kyeong‐Hyeon , Ha Yun‐Sok , Choi Seock‐Hwan , Kim Bum Soo , Kim Hyun Tae , Yoo Eun Sang , Kwon Tae Gyun , Lee Jun Nyung , Kim Tae‐Hwan 
Published: October 2018

Background and ObjectivesThe adrenal gland is a frequent site for metastasis, and a solitary adrenal mass is often observed during staging workup or imaging follow‐up in patients with extra‐adrenal malignancy. To create an appropriate management plan, it is essential to distinguish between benign adrenal lesions and metastasis in patients with extra‐adrenal cancer having solitary adrenal masses. Therefore, here we evaluated the predictive factors for adrenal metastasis in patients with extra‐adrenal malignancy having solitary adrenal mass.Materials and MethodsFrom September 2003 to June 2016, we retrospectively reviewed patients with extra‐adrenal malignancy having solitary adrenal mass on a cancer staging workup or follow‐up study who subsequently underwent adrenalectomy at our institution. All patients underwent preoperative functional studies; those with positive results were excluded from this study. Characteristics of oncology patients with adrenal mass including age, sex, body mass index, smoking, mass location, mass size, hypertension, diabetes mellitus, precontrast Hounsfield unit (HU), and synchronous or metachronous adrenal mass based on the time of the extra‐adrenal cancer diagnosis were analyzed.ResultsOf the total 68 patients with extra‐adrenal cancer having solitary adrenal mass, 22 had pathologically confirmed adrenal metastasis. Primary cancers consisted of hepatocellular cell carcinoma (n = 7), renal cell carcinoma (n = 7), lung cancer (n = 4), colon cancer (n = 3), and breast cancer (n = 1). On multivariate analysis, a higher precontrast HU (P = 0.001, odds ratio [OR] = 1.105, 95% confidence interval [CI] = 1.042‐1.172), male sex (
P = 0.019, OR = 9.782, 95% CI = 1.462‐65.461), and metachronous adrenal mass (
P = 0.007, OR = 11.090, 95% CI = 1.937‐63.490) were observed as predictive factors for adrenal metastasis in patients with extra‐adrenal cancer having solitary adrenal mass. The cut‐off value of precontrast HU to distinguish between metastasis and benign lesions was 36.2 (sensitivity = 81.8%; specificity = 91.3%).ConclusionHigh precontrast HU (> 36), male sex, and metachronous adrenal mass are predictive factors for adrenal metastasis in patients with extra‐adrenal malignancy having solitary adrenal mass.
The distribution pattern of metastatic lymph nodes after non‐curative endoscopic resection in early gastric cancer
Authors: Arroyo‐Martinez Quetzalihuitl , Han Won Ho , Eom Bang Wool , Yoon Hong Man , Kim Young Il , Cho Soo Jeong , Lee Jong Yeul , Kim Chan Gyoo , Morales‐Conde Salvador , Padillo‐Ruiz Javier , Kook Myeong‐Cherl , Choi Il Ju , Kim Young Woo , Ryu Keun Won 
Published: October 2018

Background and ObjectivesAdditional surgery should be done after non‐curative endoscopic resection (ER) in early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM). However, the distribution pattern of LNM in these patients is complicated and unpredictable. The aim of this study is to identify any different distribution patterns of LNM in patients with EGC who underwent additional surgery after non‐curative (ER) comparing to those without ER.MethodsPatients who underwent surgery for EGC between 2001 and 2016 were included. Enrolled patients were divided into two groups, those who underwent additional surgery after non‐curative ER and those who underwent direct surgery without a history of ER. Demographics, tumor characteristics and LNM distribution pattern were analyzed.ResultsAmong 4295 patients with EGC, 404 patients had a history of preoperative ER, and 3891 patients did not. After the application of exclusion criteria, 23 (7.1%) of 322 patients undergoing additional surgery had LNM. The additional surgery group showed less LNM, fewer nodal stations and more restricted distribution pattern of LNM.ConclusionsThe distribution pattern of LNM in EGC is complicated. However, more restricted locoregional LNM could be expected in cases of additional surgery after non‐curative ER than after direct surgery.
Critical evaluation of microextraction pretreatment techniques—Part 2: Membrane‐supported and homogenous phase based techniques
Authors: Havlikova Martina , Cabala Radomir , Pacakova Vera , Bosakova Zuzana 
Published: October 2018

AbstractThis review follows up on Part 1, which focused on classification and evaluation of single drop and sorbent‐based microextraction techniques. Membrane‐ and homogenous phase‐based microextraction techniques are discussed and classified in Part 2. These techniques are more recent than those in Part 1 and considerable attention has been paid to their development. The new methodologies are more sensitive and, thanks to their miniaturization, they can be classified as “green”, but no exhaustive classification is available. We hope that this review will contribute to better orientation in these methods.