bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiapoptosis effect of ZiShen prescription to increase learning and memory abilities of compound Alzheimer's disease model rats
Authors: Wei Zhiqiang , Zhang Yu , Chen Yan , Xia Xiaoshuang , Zheng Boyu , Sun Xugang , Zhang Guangming , Wang Ling , Zhang Qi , Xu Chen , Jiang Shihe , Li Xiulian , Xie Bingxin , Liao Xiaohui , Ai Zhu , Li Xin 
Published: February 2019

AbstractAlzheimer's disease (AD) is a neurodegenerative disease characterized progressive memory loss and cognitive impairment. In previous studies, the activities of extracts of Chinese medicinal herbs to treat brain function disorders caused by AD have already been reported. ZiShen prescription was a traditional Chinese medicine (TCM) compound prescription reformed for AD disease based on the basic theory of TCM. To explore the effect of ZiShen (kidney‐reinforcing) prescription on the learning and memory abilities, we made compound AD model rats by injecting d‐galactose and ibotenic acid into the abdominal cavity to damage both sides of the nucleus basalis of Meynert with ibotenic acid. The trisected Y‐maze was used to test the learning and memory abilities of AD model rats before and after treatment by ZiShen prescription and Piracetam. To investigate the mechanism of ZiShen prescription, the expressions of apoptosis‐related genes (Bcl‐2/Bax) in the cortex and hippocampus of compound AD model rats were detected in the cortex and hippocampus. The results show that, comparing with Piracetam, a clinical medicine to promote the thinking and memory for AD patients, ZiShen prescription significantly increased the learning and memory abilities of the compound AD model rats. After the treatment of ZiShen prescription, the expression of Bcl‐2 was upregulated, along with a downregulation of Bax in the cortex and hippocampus of compound AD model rats. And the results indicated that the clinical benefits of ZiShen prescription were slightly better than Piracetam. Still, further well‐designed studies are required to ensure the clinical effect of ZiShen.
Expression profiling analysis of long noncoding RNAs in a mouse model of ventilator‐induced lung injury indicating potential roles in inflammation
Authors: Zhang Nan‐Nan , Zhang Yi , Wang Lu , Xia Jin‐Gen , Liang Shun‐Tao , Wang Yan , Wang Zhi‐Zhi , Huang Xu , Li Min , Zeng Hui , Zhan Qing‐Yuan 
Published: February 2019

AbstractThe key regulators of inflammation underlying ventilator‐induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA‐mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C‐X‐C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA‐mediated regulatory patterns may contribute to VILI inflammation.
Tracking methods and retention for a longitudinal sample of alcohol‐ and drug‐involved women on probation and parole
Authors: Northcutt Bohmert Miriam , Hoskins Kayla M. , Morash Merry 
Published: February 2019

AbstractAttrition, or the progressive loss of individuals from a sample, poses a major problem in fields that carry out research to inform policy and program design. Attrition reduces statistical power by reducing sample size and compromises the external validity of findings by introducing sampling bias. If sampling bias results from disadvantages that act as barriers to research participation, then it promotes social injustice by excluding disadvantaged groups from the study. This study describes strategies used to retain participants in a longitudinal study of experiences of women under community supervision (probation or parole). It uses quantitative methods to examine sampling bias and qualitative methods to elicit accounts of participants’ explanations for being hard to reach and their recommendations for retention in future research. For participants who were and who were not retained, there were no statistically significant differences on several common quantitative predictors of retention. Hard‐to‐reach women identified residential mobility, low income, and busy lifestyles as main reasons research staff had difficulty contacting them and recommended repeated attempts at contact through multiple means. The article ends with recommendations for limiting attrition of disadvantaged, justice‐involved women in studies, and for steps to be taken when women are especially difficult to contact.
NK007 helps in mitigating paclitaxel resistance through p38MAPK activation and HK2 degradation in ovarian cancer
Authors: Li Zhenhua , Tang Xin , Luo Yu , Chen Bangyu , Zhou Congcong , Wu Xiuqing , Tang Zhenping , Qi Xiaojie , Cao Guangchao , Hao Jianlei , Liu Zonghua , Wang Qingmin , Yin Zhinan , Yang Hengwen 
Published: February 2019

AbstractOvarian cancer resistance to available medicines is a huge challenge in dire need of a solution, which makes its recurrence and mortality rate further exacerbated. A promising approach to overcome chemoresistance is drug screening from natural products. Here, we report that NK007, a (±)‐tylophorine malate isolated from the Asclepiadaceae family, selectively inhibited the proliferation of A2780 and A2780 (Taxol) cells and migration of paclitaxel‐sensitive and ‐resistant ovarian cancer cells. Interestingly, the decline of cell viability, including cell multiplication, clonality, and migration capacity was independent on cell apoptosis. At the molecular level, NK007 considerably induced G1/S arrest and upregulated the expression of phospho‐p38 mitogen‐activated protein kinase (p‐p38MAPK). In addition, hexokinase 2 (HK2) protein degradation was considerably elevated in the presence of NK007, which resulted in the reduction of oxygen consumption rate and extracellular acidification rate. Altogether, our results indicate that NK007, an analog of tylophorine, can overcome paclitaxel (PTX) resistance through p38MAPK activation and HK2 degradation. As an effective, alternative antiresistance agent, NK007 exhibits a promising potential to treat PTX‐resistant ovarian cancer.
Retracted: The role of HOTAIR‐induced downregulation of microRNA‐126 and interleukin‐13 in the development of bronchial hyperresponsiveness in neonates
Authors: Wu Dong‐Mei , Zheng Zi‐Hui , Wang Shan , Wen Xin , Han Xin‐Rui , Wang Yong‐Jian , Shen Min , Fan Shao‐Hua , Zhang Zi‐Feng , Shan Qun , Li Meng‐Qiu , Hu Bin , Zheng Yuan‐Lin , Chen Gui‐Quan , Lu Jun 
Published: February 2019

AbstractLong noncoding RNAs, including HOTAIR, are involved in the pathogenesis of a wide range of diseases. This study aimed to explore the mechanism underlying the involvement of HOTAIR in neonatal bronchial hyperresponsiveness (BHR). A total of 105 newborns were recruited in this study to collect their peripheral blood mononuclear cell and serum samples, which were then divided into different genotype groups based on the genotypes of rs4759314, rs874945, and rs7958904. The real‐time polymerase chain reaction, western blot analysis, computational analyses, and luciferase assays were performed to establish the regulatory relationships between the HOTAIR, microRNA‐126 (miR‐126), and interleukin‐13 (IL‐13). The level of HOTAIR, miR‐126, and IL‐13 among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups was similar. However, the level of HOTAIR was increased in the rs7958904 GG group, accompanied by a decreased level of miR‐126 and IL‐13. In addition, the level of airway responsiveness was comparable among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups. However, the airway responsiveness in the groups rs7958904 CG and CC was much stronger than that of the GG group. We also demonstrated that, by directly binding to miR‐126, HOTAIR reduced the expression of miR‐126, which in turn decreased the expression of IL‐13. In summary, we demonstrated the role of HOTAIR‐induced downregulation of miR‐126 and IL‐13 in the development of BHR in neonates.
Preparation of novel cisplatin‐conjugated hollow gold nanospheres for targeting cervical cancer
Authors: Guan Yong‐Hong , Tian Miao , Liu Xian‐Ying , Wang Yi‐Nan 
Published: February 2019

AbstractCervical cancer is a deadly gynecological malignancy in need of innovative treatment strategies. Emerging preclinical data has suggested the benefits of nanocarriers over the traditional chemotherapy for cancer treatment. In particular, gold nanoparticles are gaining popularity due to gold's inert nature, limited side effects, good cytocompatibility, and flexibility in preparation/modification. We conjugated polyethylene glycol (PEG) with hollow gold nanospheres (HGNs) and loaded the pegylated HGNs with an anticancer drug, cisplatin to target cervical cancer. HGNs were irradiated with noninfrared laser to increase the penetration of drug into tumor tissue and improve the delivery of cisplatin. We investigated the comparative characterization studies of prepared cisplatin loaded pegylated HGNs (cis PEG‐HGNs), free cisplatin, cisplatin loaded HGNs (cis‐HGNs), cis PEG‐HGNs without laser, and cis PEG‐HGNs with laser and its effects over cervical cancer cells. Transmission electron microscopy photomicrographs confirmed the integrity of prepared HGNs. While no significant difference was observed between encapsulation efficiency and drug loading of cis‐HGNs (84.6%) and cis PEG‐HGNs (86.7%), the encapsulation efficiency increased almost twice in HGNs, compared with control gold nanoparticles (GNs) because of the hollow cavity in HGNs. In‐vitro cytotoxicity was measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay using HeLa cells. With irradiation, HGNs induced much elevated cytotoxicity. Not only HGNs were internalized by HeLa cells, they were retained in the cellular compartment. We also tested formulations in vivo and observed that the irradiated cis‐HGNs and cis PEG‐HGNs were most effective in regressing tumors in mice.
Retracted: Icariin attenuates methotrexate chemotherapy‐induced bone marrow microvascular damage and bone loss in rats
Authors: Hassanshahi Mohammadhossein , Su Yu‐Wen , Khabbazi Samira , Fan Chia‐Ming , Tang Qian , Wen Xuesen , Fan Jian , Chen Ke‐Ming , Xian Cory J. 
Published: February 2019

AbstractMethotrexate (MTX), a widely used antimetabolite in paediatric cancer to treatment, has been widely reported to cause bone loss and bone marrow (BM) microvascular (particularly sinusoids) damage. Investigations must now investigate how MTX‐induced bone loss and microvasculature damage can be attenuated/prevented. In the present study, we examined the potency of icariin, an herbal flavonoid, in reducing bone loss and the dilation/damage of BM sinusoids in rats caused by MTX treatment. Groups of young rats were treated with five daily MTX injections (0.75 mg/kg) with and without icariin oral supplementation until Day 9 after the first MTX injection. Histological analyses showed a significant reduction in the bone volume/tissue volume (BV/TV) fraction (%) and trabecular number in the metaphysis trabecular bone of MTX‐treated rats, but no significant changes in trabecular thickness and trabecular spacing. However, the BV/TV (%) and trabecular number were found to be significantly higher in MTX + icariin‐treated rats than those of MTX alone‐treated rats. Gene expression analyses showed that icariin treatment maintained expression of osteogenesis‐related genes but suppressed the induction of adipogenesis‐related genes in bones of MTX‐treated rats. In addition, icariin treatment attenuated MTX‐induced dilation of BM sinusoids and upregulated expression of endothelial cell marker CD31 in the metaphysis bone of icariin + MTX‐treated rats. Furthermore, in vitro studies suggest that icariin treatment can potentially enhance the survival of cultured rat sinusoidal endothelial cells against cytotoxic effect of MTX and promote their migration and tube formation abilities, which is associated with enhanced production of nitric oxide.
SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9
Authors: Tanigawa Kazufumi , Maekawa Masashi , Kiyoi Takeshi , Nakayama Jun , Kitazawa Riko , Kitazawa Sohei , Semba Kentaro , Taguchi Tomohiko , Akita Satoshi , Yoshida Motohira , Ishimaru Kei , Watanabe Yuji , Higashiyama Shigeki 
Published: February 2019

AbstractAngiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High‐level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
In vitro and in vivo studies of antiosteosarcoma activities of formononetin
Authors: Hu Wei , Wu Xianpei , Tang Jiandong , Xiao Niansu , Zhao Guoping , Zhang Li , Ou Luanhai 
Published: February 2019

AbstractOsteogenic sarcoma (OGS) is a primary bone cancer, characterized by aggressive neoplasm from mesenchymal oncogenesis. However, the clinical therapeutic regimen against OGS is limited. Therefore, potential medication warrants to be further developed. Our previous study indicates that formononetin (FN) exerts effective pharmacological activity against OGS. This study aimed to further decipher the molecular mechanism behind this benefit. Patients with OGS were recruited for clinical data assay and immunoassay. Human OGS cell line (U2OS) and tumor‐bearing nude mice were subjected to a battery of biochemical analyses and immunoassays for integrative evaluation of FN‐exerted anti‐OGS effects. In human data, OGS samples showed increased expressions of ERα, p‐PI3KCATyr317, and p‐AKT
Ser473 proteins, followed by notably upregulated miR‐375 content in comparison with that in OGS‐free. In addition, FN‐treated U2OS cells showed inhibited cell proliferation, elevated lactic dehydrogenase production and lowered endogenous miR‐375 level in cells. Further, reduced immunopositive cells of Ki‐67, p‐PI3KCA
Tyr317, and p‐AKT
Ser473 were observed by the treatments of FN, while the intracellular Bax‐ and Apaf‐1‐positive cells were increased dose‐dependently. Beneficially, FN‐treated tumor‐bearing mice exhibited reduced tumor mass and intercellular miR‐375 expression. Meanwhile, immuno‐labeled cells and proteins of Bax, Caspase‐3, and Apaf‐1 in FN‐treated mice were increased dose‐dependently, whereas ERα, p‐PI3KCA
Tyr317, and p‐AKT
Ser473 positive cells and proteins were downregulated, respectively. Collectively, our current results elucidate that FN exerts effective therapeutic benefits against OGS, and the pharmacological mechanism may be related to promoting cell apoptosis by inactivating intracellular miR‐375/ERα−PI3K/AKT cascaded pathway.
Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos
Authors: An Quanli , Peng Wei , Cheng Yuyao , Lu Zhenzhen , Zhou Chuan , Zhang Yong , Su Jianmin 
Published: February 2019

AbstractOocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species. In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10−9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome‐wide expression analysis of genes in melatonin‐treated and nontreated oocytes was also conducted by high‐throughput RNA sequencing. Our results indicated that melatonin ameliorates oocyte oxidative stress and improves subsequent in vitro development of bovine cloned embryos.
Oroxylin A increases the sensitivity of temozolomide on glioma cells by hypoxia‐inducible factor 1α/hedgehog pathway under hypoxia
Authors: Wei Mian , Ma Rong , Huang Shaoliang , Liao Yan , Ding Youxiang , Li Zhaohe , Guo Qinglong , Tan Renxiang , Zhang Lulu , Zhao Li 
Published: February 2019

AbstractMicroenvironmental hypoxia‐mediated drug resistance is responsible for the failure of cancer therapy. To date, the role of the hedgehog pathway in resistance to temozolomide (TMZ) under hypoxia has not been investigated. In this study, we discovered that the increasing hypoxia‐inducible factor 1α (HIF‐1α) activated the hedgehog pathway in hypoxic microenvironment by promoting autocrine secretion of sonic hedgehog protein (Shh), and then upregulating transfer of Gli1 to the nucleus, finally contributed to TMZ resistance in glioma cells. Oroxylin A (C16H12O5), a bioactive flavonoid, could induce HIF‐1α degradation via prolyl‐hydroxylases–VHL signaling pathway, resulting in the inactivation of the hedgehog. Besides, oroxylin A increased the expression of Sufu, which is a negative regulator of Gli1. By this mechanism, oroxylin A sensitized TMZ on glioma cells. U251 intracranial transplantation model and GL261 xenograft model were used to confirm the reversal effects of oroxylin A in vivo. In conclusion, our results demonstrated that HIF‐1α/hedgehog pathway conferred TMZ resistance under hypoxia, and oroxylin A was capable of increasing the sensitivity of TMZ on glioma cells in vitro and in vivo by inhibiting HIF‐1α/hedgehog pathway and depressing the activation of Gli1 directly.
Genetic discoveries and advances in late‐onset Alzheimer’s disease
Authors: Rezazadeh Maryam , Hosseinzadeh Hassan , Moradi Mohsen , Salek Esfahani Behnaz , Talebian Shahrzad , Parvin Shaho , Gharesouran Jalal 
Published: February 2019

AbstractAlzheimer’s disease (AD) is a heterogeneous disorder with multiple patterns of clinical manifestations. Recently, due to the advance of linkage studies, next‐generation sequencing and genome‐wide association studies, a large number of putative risk genes for AD have been identified using acquired genome mega data. The genetic association between three causal genes, including amyloid precursor protein, presenilin1, and presenilin2 in early‐onset AD (EOAD), was discovered over the past few decades. These discoveries showed that there should be additional genetic risk factors for both EOAD and late‐onset AD (LOAD) to help fully explain the leading molecular mechanisms in a single pathophysiological entity. This study reviews the clinical features and genetic etiology of LOAD and discusses a variety of AD‐mediated genes that are involved in cholesterol and lipid metabolism, endocytosis, and immune response according to their mutations for more efficient selection of functional candidate genes for LOAD. New mechanisms and pathways have been identified as a result.
Absence of Drug‐Drug Interaction of Anastrozole on Levonorgestrel Delivered Simultaneously by an Intravaginal Ring: Results of a Phase 2 Trial
Authors: Nave Rüdiger , Mellinger Uwe , Klein Stefan , Höchel Joachim , Schmitz Heinz 
Published: February 2019

AbstractIntravaginal rings (IVRs) are an established option for continuous administration of drugs in women. The combination of anastrozole (ATZ) and levonorgestrel (LNG) in an IVR with an intended 4‐week wearing period has been considered for long‐term treatment of endometriosis‐associated pelvic pain. A randomized, parallel‐group, multicenter phase 2b study to assess the efficacy and safety of different dose combinations in women with symptomatic endometriosis has recently been performed. This paper will focus on the investigation of pharmacokinetic (PK) effects of ATZ on LNG using data collected from this study. Two hundred sixteen patients were randomized to the treatment group with IVRs releasing LNG 40 μg/day alone or in combination with ATZ 300 μg/day, 600 μg/day, or 1050 μg/day for 12 weeks. PK blood samples were taken before dosing and before IVR replacement or removal (days 28, 56, and 84). The primary PK parameter was the plasma concentration in apparent steady state of ATZ and LNG at the end of each IVR wearing period. Results of PK analysis demonstrate that ATZ concentrations increased proportionally with increasing dose (geometric mean values of 7.85, 15.48, and 22.61 μg/L at 300, 600, and 1050 μg/day nominal release, respectively). All point estimates for LNG concentration in apparent steady state ratios between the mono and combination IVR groups were close to 1, and the 90% confidence interval limits were in the 0.80 to 1.25 range (1.01 [0.85‐1.19], 1.03 [0.88‐1.20], 0.94 [0.80‐1.10]). In conclusion, our data indicate there is no evidence of drug‐drug interaction of ATZ on LNG.