bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat stress induces distinct responses in porcine cumulus cells and oocytes associated with disrupted gap junction and trans‐zonal projection colocalization
Authors: Yin Chao , Liu Jie , He Bin , Jia Longfei , Gong Yabin , Guo Huiduo , Zhao Ruqian 
Published: October 2018

AbstractCumulus cells (CCs), the granulosa cells surrounding the oocytes, play critical roles in oocytes maturation through intercellular communication by extending trans‐zonal projections (TZPs) to contact oocytes via gap junctions (GJs). The adverse effect of heat stress (HS) on oocyte maturation has been well documented, whereas the HS responses of CCs and the oocytes in association with GJ/TZP colocalization remain unclear. In this study, porcine cumulus‐oocyte complexes (COCs) were subjected to HS at 41.5°C for 24 hr during in vitro maturation. Cumulus expansion was impaired and oocyte quality was reduced with lower survival rate, polar body extrusion rate, and early embryo developmental potentials. CCs and oocytes isolated from COCs demonstrated distinct responses to HS. The messenger RNA abundance of heat shock protein‐related genes and mitochondrial DNA‐encoded genes, together with ATP content, were significantly increased in CCs, yet decreased in oocytes, despite activation of caspase 3 detected in both CCs and oocytes. Similar changes were observed when denuded oocytes and isolated CCs subjected to HS separately, except mitochondria reactive oxygen species (mROS). In heat‐stressed COCs, mROS was significantly increased only in oocytes. However, when isolated CCs and denuded oocytes were heat‐stressed separately, mROS was significantly increased only in CCs. Moreover, F‐actin, a TZP marker, and its colocalization with a GJ protein connexin‐45, were significantly reduced in heat‐exposed COCs. These results indicate that HS induces distinct responses in porcine CCs and oocytes in association with disrupted GJ and TZP colocalization.
MiR‐128‐3p accelerates cardiovascular calcification and insulin resistance through ISL1‐dependent Wnt pathway in type 2 diabetes mellitus rats
Authors: Wang Xin‐Yong , Zhang Xian‐Zhao , Li Feng , Ji Qing‐Rong 
Published: October 2018

AbstractVascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR‐128‐3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet β‐cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR‐128‐3p, ISL1, and the Wnt signaling pathway‐ and apoptosis‐related genes. Finally, apoptosis of islet β‐cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet β‐cell function were decreased. Furthermore, upregulation of miR‐128‐3p and ISL1 gene silencing promoted the expression of Wnt‐1, β‐catenin, GSK‐3β, and Bax and the phosphorylation of β‐catenin and GSK‐3β, inhibited c‐fos, PDX‐1, and Bcl‐2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR‐128‐3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR‐128‐3p may serve as a potential target for the treatment of T2DM.
Long noncoding RNA OPA‐interacting protein 5 antisense transcript 1 upregulated SMAD3 expression to contribute to metastasis of cervical cancer by sponging miR‐143‐3p
Authors: Chen Xing , Xiong Dongsheng , Yang Huichun , Ye Liya , Mei Shuangshuang , Wu Jinhong , Chen Shanshan , Shang Xianwen , Wang Kai , Huang Lingfei 
Published: October 2018

AbstractObjectivesSMAD3 is pivotal in the biology functions of various tumors. This study is aiming to study the relationship among SMAD3, long noncoding RNAs (lncRNAs) OPA‐interacting protein 5 antisense transcript 1 (OIP5‐AS1), and miR‐143‐3p, and their effects on cervical cancer.MethodsIn our research, real‐time polymerase chain reaction and western blot assay were conducted to detect the expression level of messenger RNA and protein in tumor tissues and cells. Transfection of lncRNA OIP5‐AS1, miR‐143‐3p, or SMAD3 was performed to investigate their potential effects on the function of cell as well as the relationship among them in cervical cell lines via 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide) together with transwell assays or dual‐luciferase reporter assay respectively.ResultsSMAD3, lncRNA OIP5‐AS1 expression is significantly enhanced in cervical cancer tissues and cell lines, but miR‐143‐3p was inhibited. LncRNA OIP5‐AS1 is demonstrated to mediate the physiological process of cervical cancer cells. Moreover, silencing SMAD3 via siRNA suppressed cell number, viability, migration and invasion, whereas overexpression of OIP5‐AS1 promoted these abilities. Furthermore, lncRNA OIP5‐AS1 exert its function via sponging miR‐143‐3p to regulate SMAD3 expression.ConclusionsLncRNA OIP5‐AS1 promoted SMAD3 expression via mediating miR‐143‐3p to promote migration and invasion of cervical cancer cells.
Circular RNA in cardiovascular disease
Authors: Altesha M‐Ashraf , Ni Tiffany , Khan Afaan , Liu Kexiang , Zheng Xiufen 
Published: October 2018

AbstractCircular RNA (circRNA) are endogenous transcripts that display differential expression across species, developmental stages, and pathologies. Their lack of free ends confers increased stability when compared with linear transcripts, making them ideal candidates for future diagnostic biomarkers and therapeutic interventions. Increasing evidence has implicated circRNA in the pathogenesis of multiple cardiovascular diseases. In this paper, we summarize current understanding of circRNA biogenesis, properties, expression profiles, detection methods, functions, and their implication in cardiac pathologies including/ischemia reperfusion injury, myocardial infarction, cardiac senescence, cardiac fibrosis, cardiomyopathy, cardiac hypertrophy and heart failure, atherosclerosis, coronary artery disease, and aneurysm.
Helvolic acid attenuates osteoclast formation and function via suppressing RANKL‐induced NFATc1 activation
Authors: Chen Kai , Yuan Yu , Wang Ziyi , Song Dezhi , Zhao Jinmin , Cao Zhen , Chen Junhao , Guo Qiang , Chen Li , Tickner Jennifer , Xu Jiake 
Published: October 2018

AbstractExcessive osteoclast formation and function are considered as the main causes of bone lytic disorders such as osteoporosis and osteolysis. Therefore, the osteoclast is a potential therapeutic target for the treatment of osteoporosis or other osteoclast‐related diseases. Helvolic acid (HA), a mycotoxin originally isolated from Aspergillus fumigatus , has been discovered as an effective broad‐spectrum antibacterial agent and has a wide range of pharmacological properties. Herein, for the first time, HA was demonstrated to be capable of significantly inhibiting receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis and bone resorption in vitro by suppressing nuclear factor of activated T cells 1 (NFATc1) activation. This inhibition was followed by the dramatically decreased expression of NFATc1‐targeted genes including
Ctr (encoding calcitonin receptor),
Acp5 (encoding tartrate‐resistant acid phosphatase [TRAcP]),
Ctsk (encoding cathepsin K),
Atp6v0d2 (encoding the vacuolar H+ ATPase V0 subunit d2 [V‐ATPase‐d2]) and
Mmp9 (encoding matrix metallopeptidase 9) which are osteoclastic‐specific genes required for osteoclast formation and function. Mechanistically, HA was shown to greatly attenuate multiple upstream pathways including extracellular signal‐regulated kinase (ERK) phosphorylation, c‐Fos signaling, and intracellular Ca
2+ oscillation, but had little effect on nuclear factor‐κB (NF‐κB) activation. In addition, HA also diminished the RANKL‐induced generation of intracellular reactive oxygen species. Taken together, our study indicated HA effectively suppressed RANKL‐induced osteoclast formation and function. Thus, we propose that HA can be potentially used in the development of a novel drug for osteoclast‐related bone diseases.
Colorectal cancer invasiveness in vitro: Predominant contribution of neonatal Nav1.5 under normoxia and hypoxia
Authors: Guzel R. Mine , Ogmen Kazim , Ilieva Kristina M. , Fraser Scott P. , Djamgoz Mustafa B. A. 
Published: October 2018

AbstractFunctional expression of voltage‐gated Na+ channels (VGSCs) occurs in human carcinomas and promotes invasiveness in vitro and metastasis in vivo. Both neonatal and adult forms of Nav1.5 (nNav1.5 and aNav1.5, respectively) have been reported to be expressed at messenger RNA (mRNA) level in colorectal cancer (CRCa) cells. Here, three CRCa cell lines (HT29, HCT116 and SW620) were studied and found to express nNav1.5 mRNA and protein. In SW620 cells, adopted as a model, effects of gene silencing (by several small interfering RNAs [siRNAs]) selectively targeting nNav1.5 or aNav1.5 were determined on (a) channel activity and (b) invasiveness in vitro. Silencing nNav1.5 made the currents more “adult‐like” and suppressed invasion by up to 73%. Importantly, subsequent application of the highly specific, general VGSC blocker, tetrodotoxin (TTX), had no further effect. Conversely, silencing aNav1.5 made the currents more “neonatal‐like” but suppressed invasion by only 17% and TTX still induced a significant effect. Hypoxia increased invasiveness and this was also blocked completely by siRNA targeting nNav1.5. The effect of hypoxia was suppressed dose dependently by ranolazine, but its effect was lost in cells pretreated with nNav1.5‐siRNA. We conclude that (a) functional nNav1.5 expression is common to human CRCa cells, (b) hypoxia increases the invasiveness of SW620 cells, (c) the VGSC‐dependent invasiveness is driven predominantly by nNav1.5 under both normoxic and hypoxic conditions and (d) the hypoxia‐induced increase in invasiveness is likely to be mediated by the persistent current component of nNav1.5.
Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers
Authors: Liu Ji‐Long , Zhang Wen‐Qian , Zhao Miao , Huang Ming‐Yu 
Published: October 2018

AbstractGrowing evidence from recent studies has shown that the X‐inactive specific transcript (XIST), a well‐known long noncoding RNA involved in early embryonic development, is aberrantly regulated in various human cancers. However, the prognostic value of XIST in cancers remains uncharacterized. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies, and a meta‐analysis was performed to explore the association of XIST expression with overall survival (OS) and clinicopathological parameters. We demonstrated that high XIST expression was associated with poor OS (hazard ratio = 1.76; 95% confidence intervals [CI], 1.56–1.98; p < 0.001). In addition, increased XIST expression was found to be associated with lymph node metastasis (odds ratio [OR] = 2.06; 95% CI, 1.46–1.90;
p < 0.001), distant metastasis (OR = 2.93; 95% CI, 2.00–4.28;
p < 0.001), tumor size (OR = 2.66; 95% CI, 1.86–3.81;
p < 0.001), poor differentiation (OR = 1.45; 95% CI, 1.00–2.10;
p = 0.049), and advanced tumor stage (OR = 3.35; 95% CI, 2.25–5.00;
p < 0.001), but not with age (OR = 0.82; 95% CI, 0.59–1.15;
p = 0.251) or gender (OR = 0.92; 95% CI, 0.70–1.19;
p = 0.512). Our meta‐analysis showed that XIST may be a useful common biomarker for predicting prognosis in patients with cancer.
miR‐335‐5p induces insulin resistance and pancreatic islet β‐cell secretion in gestational diabetes mellitus mice through VASH1‐mediated TGF‐β signaling pathway
Authors: Tang Xu‐Wen , Qin Qing‐Xin 
Published: October 2018

AbstractMultiple studies have reported different methods in treating gestational diabetes mellitus (GDM); however, the relationship between miR‐335‐5p and GDM still remains unclear. Here, this study explores the effect of miR‐335‐5p on insulin resistance and pancreatic islet β‐cell secretion via activation of the TGFβ signaling pathway by downregulating VASH1 expression in GDM mice. The GDM mouse model was established and mainly treated with miR‐335‐5p mimic, miR‐335‐5p inhibitor, si‐VASH1, and miR‐335‐5p inhibitor + si‐VASH1. Oral glucose tolerance test (OGTT) was conducted to detect fasting blood glucose (FBG) fasting insulin (FINS). The OGTT was also used to calculate a homeostasis model assessment of insulin resistance (HOMA‐IR). A hyperglycemic clamp was performed to measure the glucose infusion rate (GIR), which estimated β‐cell function. Expressions of miR‐335‐5p, VASH1, TGF‐β1, and c‐Myc in pancreatic islet β‐cells were determined by RT‐qPCR, western blot analysis, and insulin release by ELISA. The miR‐335‐5p mimic and si‐VASH1 groups showed elevated blood glucose levels, glucose area under the curve (GAUC), and HOMA‐IR, but a reduced GIR and positive expression of VASH1. Overexpression of miR‐335‐5p and inhibition of VASH1 contributed to activated TGFβ1 pathway, higher c‐Myc, and lower VASH1 expressions, in addition to downregulated insulin and insulin release levels. These findings provided evidence that miR‐335‐5p enhanced insulin resistance and suppressed pancreatic islet β‐cell secretion by inhibiting VASH1, eventually activating the TGF‐β pathway in GDM mice, which provides more clinical insight on the GDM treatment.
Runx2 is required for postnatal intervertebral disc tissue growth and development
Authors: Liao Lifan , Jiang Hua , Fan Yunshan , Lu Ronald S. , Wei Changli , Takarada Takeshi , He Shisheng , Chen Di 
Published: October 2018

AbstractRunx2 plays an essential role in embryonic disc tissue development in mice. However, the role of runt‐related transcription factor 2 (Runx2) in postnatal disc tissue growth and development has not been defined. In the present studies, we generated Runx2 conditional knockout (KO) mice (Runx2Agc1ER), in which Runx2 was deleted in Aggrecan‐expressing cells in disc tissue at postnatal 2‐weeks of age. We then analyzed changes in disc tissue growth and development using histology and immunohistochemical methods in 3‐month‐old mice. We found that large vacuolated notochordal cells were accumulated in the nucleus pulposus (NP) in Runx2 KO mice. The growth plate cartilage tissue in the disc was thicker in Runx2 KO mice. We also found a significant upregulation of Indian hedgehog (Ihh) expression in the cells in NP cells and in annulus fibrosus cells of Runx2 KO mice. These results demonstrated that Runx2 may play an important role in postnatal disc tissue development through interacting with Ihh signaling.
Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria
Authors: Bernardini Giulia , Leone Gemma , Millucci Lia , Consumi Marco , Braconi Daniela , Spiga Ottavia , Galderisi Silvia , Marzocchi Barbara , Viti Cecilia , Giorgetti Giovanna , Lupetti Pietro , Magnani Agnese , Santucci Annalisa 
Published: October 2018

AbstractAlkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2‐dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin‐like polymer that progressively deposits onto connective tissues causing a pigmentation called “ochronosis” and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis. We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell–matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGA‐treated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU.
Necrosis and necroptosis in germ cell depletion from mammalian ovary
Authors: Chaudhary Govind R. , Yadav Pramod K. , Yadav Anil K. , Tiwari Meenakshi , Gupta Anumegha , Sharma Alka , Sahu Kankshi , Pandey Ashutosh N. , Pandey Ajai K. , Chaube Shail K. 
Published: October 2018

AbstractThe maximum number of germ cells is present during the fetal life in mammals. Follicular atresia results in rapid depletion of germ cells from the cohort of the ovary. At the time of puberty, only a few hundred (<1%) germ cells are either culminated into oocytes or further get eliminated during the reproductive life. Although apoptosis plays a major role, necrosis as well as necroptosis, might also be involved in germ cell elimination from the mammalian ovary. Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise. Necroptosis is initiated by tumor necrosis factor and operated through receptor interacting protein kinase as well as mixed lineage kinase domain‐like protein. The acetylcholinesterase, cytokines, starvation, and oxidative stress play important roles in necroptosis‐mediated granulosa cell death. The granulosa cell necroptosis directly or indirectly induces susceptibility toward necroptotic or apoptotic cell death in oocytes. Indeed, prevention of necrosis and necroptosis pathways using their specific inhibitors could enhance growth/differentiation factor‐9 expression, improve survivability as well as the meiotic competency of oocytes, and prevent decline of reproductive potential in several mammalian species and early onset of menopause in women. This study updates the information and focuses on the possible involvement of necrosis and necroptosis in germ cell depletion from the mammalian ovary.
Pancreatic resident endocrine progenitors demonstrate high islet neogenic fidelity and committed homing towards diabetic mice pancreas
Authors: Srivastava Abhay , Dadheech Nidheesh , Vakani Mitul , Gupta Sarita 
Published: October 2018

AbstractPancreatic progenitors have been explored for their profound characteristics and unique commitment to generate new functional islets in regenerative medicine. Pancreatic resident endocrine progenitors (PREPs) with mesenchymal stem cell (MSC) phenotype were purified from BALB/c mice pancreas and characterized. PREPs were differentiated into mature islet clusters in vitro by activin‐A and swertisin and functionally characterized. A temporal gene and protein profiling was performed during differentiation. Furthermore, PREPs were labeled with green fluorescent protein (GFP) and transplanted intravenously into streptozotocin (STZ) diabetic mice while monitoring their homing and differentiation leading to amelioration in the diabetic condition. PREPs were positive for unique progenitor markers and transcription factors essential for endocrine pancreatic homeostasis along with having the multipotent MSC phenotype. These cells demonstrated high fidelity for islet neogenesis in minimum time (4 days) to generate mature functional islet clusters (shortest reported period for any isolated stem/progenitor). Furthermore, GFP‐labeled PREPs transplanted in STZ diabetic mice migrated and localized within the injured pancreas without trapping in any other major organ and differentiated rapidly into insulin‐producing cells without an external stimulus. A rapid decrease in fasting blood glucose levels toward normoglycemia along with significant increase in fasting serum insulin levels was observed, which ameliorated the diabetic condition. This study highlights the unique potential of PREPs to generate mature islets within the shortest period and their robust homing toward the damaged pancreas, which ameliorated the diabetic condition suggesting PREPs affinity toward their niche, which can be exploited and extended to other stem cell sources in diabetic therapeutics.
Behçet’s disease: An immunogenetic perspective
Authors: Salmaninejad Arash , Zamani Mohammad Reza , Shabgah Arezoo Gowhari , Hosseini Seyedmojtaba , Mollaei Fatemeh , Hosseini Nayyerehalsadat , Sahebkar Amirhossein 
Published: October 2018

AbstractBehçet’s disease (BD) is a chronic and rare multisystemic disorder defined by autoimmunity and inflammatory characteristics, manifested by ocular lesions, recurrent genital and oral ulcers, skin symptoms and arthritis as well as neurological, intestinal, and vascular involvement. Despite the unknown cause of BD, there is some strong documentation for immunological, genetic, environmental, and infectious factors playing a role in the pathogenesis of BD. While the nature of the genetic variants remains unidentified, many genetic risk factors are considered to contribute to BD susceptibility. Along with human leukocyte antigen gene encoding B*51 (HLA‐B*51) and areas including the major histocompatibility complex class I, genome‐wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)‐10, IL‐12 receptor β 2 (IL‐12RB2), IL‐23 receptor (IL‐23R), C‐C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin‐like receptor family members (KLRC4‐KLRK1). It is believed that BD could be considered as a disorder lying in between autoimmune and autoinflammatory syndromes. The positive responses to classical immunosuppressive agents like azathioprine and cyclosporine and involvement of autoantigens in the initiation of the disorder are the main BD features that reflect the autoimmune nature of the disorder. In this review, we address recent findings on the role of common cytokines, antibodies and immunogenetic factors in BD.