bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA PVT1 regulates growth, migration, and invasion of bladder cancer by miR‐31/CDK1
Authors: Tian Zhaoju , Cao Shuang , Li Cheng , Xu Mingfang , Wei Huaiqing , Yang Han , Sun Qiyu , Ren Qikui , Zhang Le 
Published: October 2018

AbstractPurposeThe aim of our study was to validate the sway of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on the metabolism and growth of bladder cancer cells by microRNA‐31 (miR‐31)/cyclin‐dependent kinase 1 (
CDK1).MethodsThe Gene Expression Omnibus database was used for analyzing the differentially expressed lncRNA and messenger RNA (mRNA) in bladder cancer tissues, with the highly expressed lncRNA PVT1 and mRNA CDK1 screened out. The expression level of PVT1 was detected by quantitative reverse‐transcription polymerase chain reaction, cell viability by Cell Counting Kit‐8 assay, cell proliferation and scratch by 5‐bromo‐2′‐deoxyuridine assay, cell migration and invasion by transwell assays, the expression level of
CDK1 by immunohistochemistry and western blot analysis, transcription factor targeting by dual‐luciferase assay, and the effect of PVT1 on bladder cancer growth by nude mice tumor formation experiment.ResultsLncRNA PVT1 and mRNA CDK1 had a higher expression in bladder cancer cells than that in neighboring tissues. Activity, proliferation, colony formation, migration, and invasion of bladder cancer cell were noticeably reduced by the PVT1 inhibitor than that of control group. PVT1 and
CDK1 have binding sites with miR‐31. When miR‐31 decreased, CDK1 mRNA and protein levels increased in vivo experiments in nude mice. When PVT1 was downregulated, the tumor size was significantly reduced and tumor proliferation was curbed. Immunohistochemistry showed that the positive rate of
CDK1 and
Ki‐67 decreased and the expression of miR‐31 increased after PVT1 was inhibited.ConclusionsLncRNA PVT1 was overexpressed in bladder cancer cells, and it was downregulated miR‐31 to enhance CDK1 expression and facilitate bladder cancer cells proliferation, migration, and invasion.
MicroRNA‐133b suppresses bladder cancer malignancy by targeting TAGLN2‐mediated cell cycle
Authors: Zhao Feng , Zhou Liu‐Hua , Ge Yu‐Zheng , Ping Wen‐Wen , Wu Xin , Xu Zhong‐Le , Wang Min , Sha Zuo‐Liang , Jia Rui‐Peng 
Published: October 2018

AbstractMicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3′‐untranslated regions (3′‐UTRs) of target messenger RNAs. Recently, downregulation of miR‐133b has been detected in various human malignancies. Here, the potential biological role of miR‐133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR‐133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR‐133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR‐133b promoted the proliferation of BC cells, at least partially through a TAGLN2‐mediated cell cycle pathway. Our results suggest a novel miR‐133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.
The distinct role of STIM1 and STIM2 in the regulation of store‐operated Ca2+ entry and cellular function
Authors: Chen Yih‐Fung , Chen Li‐Hsien , Shen Meng‐Ru 
Published: October 2018

AbstractStromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum (ER) Ca2+ sensors that initiate store‐operated Ca
2+ entry (SOCE). The roles of STIM1‐mediated SOCE in cancer biology have been highlighted in different types of cancer, but that of STIM2 is unknown. By the model of cervical cancer, here we focus on the cooperative regulation of SOCE by STIM proteins and their distinct roles in cellular function. Immunofluorescent stainings of surgical specimens of cervical cancer show that STIM1 and STIM2 are abundant in tumor tissues, but STIM1 is the major ER Ca
2+ sensor identified in the invasive front of cancer tissues. STIM1 or STIM2 overexpression in cervical cancer SiHa cells induces an upregulated SOCE. Regarding cellular function, STIM1 and STIM2 are necessary for cell proliferation, whereas STIM1 is the dominant ER Ca
2+ sensor involved in cell migration. During SOCE, STIM1 is aggregated and translocated towards the Orai1‐containing plasma membrane in association with the microtubule plus‐end binding protein EB1. In contrast, STIM2 is constitutively aggregated without significant trafficking or association with microtubules. These results show the distinct role of STIM1 and STIM2 in SOCE and cellular function of cervical cancer cells.
Androgen receptor transcriptional activity and chromatin modifications on the ABCB1/MDR gene are critical for taxol resistance in ovarian cancer cells
Authors: Sun Nian‐Kang , Kohli Abhidha , Huang Shang‐Lang , Chang Ting‐Chang , Chao Chuck C.‐K. 
Published: October 2018

AbstractWe report here that the androgen receptor (AR) and ABCB1 are upregulated in a model of acquired taxol resistance (txr) in ovarian carcinoma cells. AR silencing sensitizes txr cells to taxol threefold, whereas ectopic AR expression in AR‐null HEK293 cells induces resistance to taxol by 1.7‐fold. AR activation using the agonist dihydrotestosterone (DHT) or sublethal taxol treatment upregulates ABCB1 expression in both txr cells and AR‐expressing HEK293 cells. In contrast, AR inactivation using the antagonist bicalutamide downregulates ABCB1 expression and enhances cytotoxicity to taxol. A functional ABCB1 promoter containing five predicted androgen‐response elements (AREs) is cloned. Deletion assays reveal a taxol‐responsive promoter segment which harbors ARE4. Notably, DHT‐ or taxol‐activated AR potentiates binding of the AR to ARE4 as revealed by the chromatin immunoprecipitation. On the other hand, txr cells display an increase in chromatin remodeling. AR/H3K9ac and AR/H3K14ac complexes bind specifically to ARE4 in response to taxol. Furthermore, acetyltransferase protein levels (p300 and GCN5) are upregulated in txr cells. Silencing of p300 or GCN5 reduces chromatin modification and enhances cytotoxicity in both parental and txr SKOV3 cells. While the phosphatidylinositol 3‐kinase (PI3K)/serine/threonine protein kinase (AKT) pathway is significantly activated by taxol, taxol‐induced ABCB1 expression, histone posttranslational modifications, and p300 binding to ARE4 are suppressed following inhibition of the PI3K/AKT cellular pathway. These results demonstrate that the AKT/p300/AR axis can be activated to target ABCB1 gene expression in response to taxol, thus revealing a new treatment target to counter taxol resistance.
Punicic acid: A potential compound of pomegranate seed oil in Type 2 diabetes mellitus management
Authors: Khajebishak Yaser , Payahoo Laleh , Alivand Mohammadreza , Alipour Beitollah 
Published: October 2018

AbstractDiabetes is one of the most prevalent diseases in the worldwide. Type 2 diabetes mellitus (T2DM), the most common form of the disease, has become a serious threat to public health and is a growing burden on global economies. Due to the unexpected adverse effects of antidiabetic medicines, the use of nutraceuticals as a complementary therapy has drawn extensive attention by investigators. In this issue, a novel nutraceutical, Punicic acid (PA)—the main ingredient of pomegranate seed oil (PSO) that has potential therapeutic effects in T2DM—has been investigated. PA is a peroxisome proliferator‐activated receptor gamma agonist, and unlike synthetic ligands, such as thiazolidinediones, it has no side effects. PA exerts antidiabetic effects via various mechanisms, such as reducing inflammatory cytokines, modulating glucose homeostasis, and antioxidant properties. In this review, we discussed the potential therapeutic effects of PSO and PA and represented the related mechanisms involved in the management of T2DM.
Diagnostic, prognostic, and therapeutic potency of microRNA 21 in the pathogenesis of colon cancer, current status and prospective
Authors: Bahreyni Amirhossein , Rezaei Melika , Bahrami Afsane , Khazaei Majid , Fiuji Hamid , Ryzhikov Mikhail , Ferns Gordon A. , Avan Amir , Hassanian Seyed Mahdi 
Published: October 2018

AbstractAberrant microRNA (miR) expression is implicated in multiple human malignancies. miR‐21, acting as a proto‐oncogene, is involved in a variety of cellular processes and tumorigenesis and is frequently overexpressed in some cancer types. Several tumor suppressors, metastatic, and apoptotic genes have been identified as miR‐21 targets, including Ras homolog gene family member B, PTEN, Sprouty2, programmed cell death 4, Integrin‐β4, and E‐cadherin thereby regulating tumor growth, invasion, and metastasis. There is a growing evidence that miR‐21 expression is associated with clinical outcomes in patients with colorectal cancer (CRC). In this review, we summarize the potential diagnostic, prognostic, and therapeutic values of miR‐21 in CRC progression for a better understanding and hence a better management of this disease.
Therapeutic use of curcumin‐encapsulated and curcumin‐primed exosomes
Authors: Oskouie Mohammad N. , Aghili Moghaddam Nazanin S , Butler Alexandra E. , Zamani Parvin , Sahebkar Amirhossein 
Published: October 2018

AbstractCurcumin, the bioactive pigment of turmeric which has polyphenolic‐hydrophobic components, has been used for the treatment of a variety of diseases. However, due to its insignificant intestinal‐liver metabolism, low stability, quick systemic elimination and its hydrophobic property with low solubility, curcumin has limited bioavailability. Exosomes are nanovesicles (30–100 nm) released from diverse cell types into extracellular and, ultimately, into bio‐fluids in a tightly regulated manner. Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell‐to‐cell contact. Curcumin‐encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation. Thus, curcumin‐encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin‐primed and curcumin‐encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.
Altered bone microarchitecture in a type 1 diabetes mouse model Ins2Akita
Authors: Carvalho Filipe R. , Calado Sofia M. , Silva Gabriela A. , Diogo Gabriela S. , Moreira da Silva Joana , Reis Rui L. , Cancela M. Leonor , Gavaia Paulo J. 
Published: October 2018

AbstractType 1 diabetes mellitus (T1DM) has been associated to several cartilage and bone alterations including growth retardation, increased fracture risk, and bone loss. To determine the effect of long term diabetes on bone we used adult and aging Ins2
Akita mice that developed T1DM around 3–4 weeks after birth. Both
Ins2
Akita and wild‐type (WT) mice were analyzed at 4, 6, and 12 months to assess bone parameters such as femur length, growth plate thickness and number of mature and preapoptotic chondrocytes. In addition, bone microarchitecture of the cortical and trabecular regions was measured by microcomputed tomography and gene expression of
Adamst‐5, Col2, Igf1, Runx2, Acp5, and
Oc was quantified by quantitative real‐time polymerase chain reaction.
Ins2
Akita mice showed a decreased longitudinal growth of the femur that was related to decreased growth plate thickness, lower number of chondrocytes and to a higher number of preapoptotic cells. These changes were associated with higher expression of
Adamst‐5, suggesting higher cartilage degradation, and with low expression levels of
Igf1 and
Col2 that reflect the decreased growth ability of diabetic mice.
Ins2
Akita bone morphology was characterized by low cortical bone area (Ct.Ar) but higher trabecular bone volume (BV/TV) and expression analysis showed a downregulation of bone markers
Acp5,
Oc, and
Runx2. Serum levels of insulin and leptin were found to be reduced at all‐time points
Ins2
Akita. We suggest that
Ins2
Akita mice bone phenotype is caused by lower bone formation and even lower bone resorption due to insulin deficiency and to a possible relation with low leptin signaling.
Myo‐inositol and D‐chiro‐inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model
Authors: Bevilacqua Arturo , Dragotto Jessica , Giuliani Alessandro , Bizzarri Mariano 
Published: October 2018

AbstractMice exposed to continuous light undergo functional and histological changes that mimic those of human Polycystic Ovary Syndrome (PCOS). We herein induced the syndrome by exposing 30‐day‐old females to 10 weeks of permanent light. Ovarian morphology and histology, as well as reproductive parameters (time of observed pregnancy/delivery) were investigated. Ovaries of PCOS‐modeled mice showed lack of tertiary follicles and corpora lutea, altered ovarian architecture, and increased thickness of the theca layer. When mice were returned to a normal light‐dark regimen for 10 days, a slight, spontaneous improvement occurred, whereas a quick and almost complete recovery from PCOS signs and symptoms was obtained by treating animals with a daily supplementation of 420 mg/kg myo‐inositol and D‐chiro‐inositol (MyoIns/DCIns) in a 40:1 molar ratio. Namely, ovaries from mice treated by this protocol recovered normal histological features and a proper ratio of theca/granulosa cell layer thickness (TGR), suggesting that the androgenic phenotype was efficiently reversed. Indeed, we identified TGR as a useful index of PCOS, as its increase in PCOS‐modeled mice correlated linearly with reduced reproductive capability (
r = 0.75,
p < 0.0001). Mice treated with a 40:1 formula regained low TGR values and faster recovery of their fertility, with a physiological delivery time after mating. On the other hand, a higher D‐chiro‐inositol treatment formula, such as MyoIns versus DCIns 5:1, was ineffective or even had a negative effect on clinical‐pathological outcomes.
Risk factors and therapies in vascular diseases: An umbrella review of updated systematic reviews and meta‐analyses
Authors: Hong Xing‐yu , Lin Jie , Gu Wei‐wei 
Published: October 2018

AbstractAberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral artery diseases. Epidemiological and basic science evidence supported genetic reasons, compounded by obesity, hypercholesterolemia, hypertension, diabetes, and smoking as risk factors. This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta‐analyses studies in PubMed, Cochrane, Embase, and Central published in January 2000–May 2018. We made qualitative eligibility gradation of the articles based on inclusion criteria, and independently extracted descriptive and methodologic data to compile their outcomes. We considered 95% confidence interval and the between‐study heterogeneity, designated by I
2. Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8, respectively, for the search terms “cardiovascular,” “renal,” “cerebral,” and “limb ischemia” each in combination with “risk factors” and “therapeutics.” Our search on genome‐wide analyses revealed genes associated with HDL‐cholesterol, matrix metalloproteases, angiogenesis, notch3, renin‐angiotensin, apolipoprotein E, insulin, and cytokine levels as critical participants in the pathogenesis of vascular diseases. Hypertension and endothelial growth factor‐linked polymorphisms were found to contribute to vascular damage. The studies reinforced that lifestyle and dietary patterns influenced susceptibility of circulatory system diseases. Additionally, endovascular medicines, surgical vascularization, angioplasty, and renal artery stenting appeared as major therapeutic approaches in vascular patients. Altogether, our review offers up‐to‐date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.
Brain‐derived neurotrophic factor alleviates the oxidative stress induced by oxygen and glucose deprivation in an ex vivo brain slice model
Authors: González‐Rodríguez Paloma , Ugidos Irene F. , Pérez‐Rodríguez Diego , Anuncibay‐Soto Berta , Santos‐Galdiano María , Font‐Belmonte Enrique , Gonzalo‐Orden José Manuel , Fernández‐López Arsenio 
Published: October 2018

AbstractBrain‐derived neurotrophic factor (BDNF) is considered as a putative therapeutic agent against stroke. Since BDNF role on oxidative stress is uncertain, we have studied this role in a rat brain slice ischemia model, which allows BDNF reaching the neural parenchyma. Hippocampal and cerebral cortex slices were subjected to oxygen and glucose deprivation (OGD) and then returned to normoxic conditions (reperfusion‐like, RL). OGD/RL increased a number of parameters mirroring oxidative stress in the hippocampus that were reduced by the BDNF presence. BDNF also reduced the OGD/RL‐increased activity in a number of antioxidant enzymes in the hippocampus but no effects were observed in the cerebral cortex. In general, we conclude that alleviation of oxidative stress by BDNF in OGD/RL‐exposed slices relies on decreasing cPLA2 activity, rather than modifying antioxidant enzyme activities. Moreover, a role for the oxidative stress in the differential ischemic vulnerability of cerebral cortex and hippocampus is also supported.
Comparing phasic dopamine dynamics in the striatum, nucleus accumbens, amygdala, and medial prefrontal cortex
Authors: Holloway Zade R. , Freels Timothy G. , Comstock Josiah F. , Nolen Hunter G. , Sable Helen J. , Lester Deranda B. 
Published: October 2018

AbstractMidbrain dopaminergic neurons project to and modulate multiple highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. Dopamine regulates behaviors associated with action selection in the striatum, reward in the nucleus accumbens (NAc), emotional processing in the amygdala, and executive functioning in the medial prefrontal cortex (mPFC). The multifunctionality of dopamine likely occurs at the individual synapses, with varied levels of phasic dopamine release acting on different receptor populations. This study aimed to characterize specific aspects of stimulation‐evoked phasic dopamine transmission, beyond simple dopamine release, using in vivo fixed potential amperometry with carbon fiber recording microelectrodes positioned in either the dorsal striatum, NAc, amygdala, or mPFC of anesthetized mice. To summarize results, the present study found that the striatum and NAc had increased stimulation‐evoked phasic dopamine release, faster dopamine uptake (leading to restricted dopamine diffusion), weaker autoreceptor functioning, greater supply levels of available dopamine, and increased dopaminergic responses to DAT blockade compared to the amygdala and mPFC. Overall, these findings indicate that phasic dopamine may have different modes of communication between striatal and corticolimbic regions, with the first being profuse in concentration, rapid, and synaptically confined and the second being more limited in concentration but longer lasting and spatially dispersed. An improved understanding of regional differences in dopamine transmission can lead to more efficient treatments for disorders related to dopamine dysfunction.
Partisan Media, Polarized Audiences? A Qualitative Analysis of Online Political News and Responses in the United States, U.K., and The Netherlands
Authors: Hameleers Michael 
Published: October 2018

Abstract
Media outlets in the United States are frequently accused of articulating partisan biases in political reporting. In Europe, the media and citizens are assumed to interpret reality from polarized and populist mindsets. To date, however, empirical research has not explored how such interpretations are constructed online. Important questions remain unanswered: How are online media constructing partisan biases? How do citizens respond to such news? To answer these questions, this article draws on a comparative qualitative content analysis of online political news and responses in the United States, U.K., and The Netherlands (N = 1,179). Results reveal that citizens respond to partisan news with congruent polarized interpretations. These findings provide important foundational evidence for the congruence between partisan media and polarized interpretations.
DNA damage dependent hypomethylation regulates the pro-angiogenic LncRNA MEG9
Authors: Espinosa-Diez Cristina , Wilson RaeAnna , Mukherjee Rishima , Feltham Marlee , Hudson Clayton , Ruhl Rebecca , Anand Sudarshan 
Published: October 2018

AbstractChanges in gene expression are key for the cells to adapt and response to intrinsic and extrinsic stimulus. It has been shown that genotoxic stress induces global hypomethylation as a result of decreased expression of DNA methyl transferases (DNMT). We hypothesized that DNA damage suppresses long non-coding RNA expression in the vasculature via DNA methylation leading to more robust DNA repair/survival or cellular senescence/death cell fate decisions. We show here that ionizing radiation reduces the expression of DNMTs in the vascular endothelium and this leads to increased expression of the anti-apoptotic lncRNA MEG9. MEG9 is a lncRNA from the DLK1-DIO3 ncRNA cluster. Loss-of-function studies using RNA gapmers indicate that MEG9 protects endothelial cells from DNA damage induced cell death. Consistent with this phenotype, knockdown of MEG9 decreases growth factor dependent angiogenesis in a 3D fibrin gel angiogenesis assay. Mechanistically, we observed that MEG9 knockdown decreased the expression of cell survival genes including survivin and induced the expression of pro-apoptotic genes such as Bad/Bax. Taken together, our findings illustrate how DNA methylation at selective lncRNA loci can regulate their expression and drive endothelial cell fate decisions.
Use of and attitudes to the role of medication for acute whiplash injury: A preliminary survey of emergency department doctors
Authors: Nikles Jane , Keijzers Gerben , De Silva Muthuwahandi Ishan Diluka , Khan Subaat , Sterling Michele 
Published: October 2018

AbstractObjectiveDescribe current practice of medication prescribing for acute whiplash‐associated disorders (WAD) in the ED and explore attitudes towards pregabalin prescription for WAD.MethodsQuestionnaire‐based survey in two EDs collected data on demographics and self‐reported medication prescribing for WAD. Comfort in various scenarios for pregabalin prescribing was rated.ResultsA total of 145/170 (85%) doctors responded; 42.8% were junior doctors. Self‐reported medications prescribed were nonsteroidal anti‐inflammatory drug (77.9% [95% confidence interval (CI) 70.1–84.2]), paracetamol (75.2% [95% CI 67.2–81.8]), opioids (43.5% [95% CI 35.3–51.9]) and benzodiazepines (11.0% [95% CI 6.6–17.6]). Most were comfortable to prescribe pregabalin in evidence‐based or advised‐by‐specialists scenarios.ConclusionsOpioids appear to be over‐prescribed. Further research into pregabalin prescription in ED is warranted.