bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐129‐5p and ‐3p co‐target WWP1 to suppress gastric cancer proliferation and migration
Authors: Ma Lianjun , Chen Xiaorui , Li Chang , Cheng Rongjie , Gao Zhuo , Meng Xiangbo , Sun Chen , Liang Chenxi , Liu Yanqing 
Published: November 2018

AbstractGastric cancer (GC) is a worldwide health problem. Uncovering the underlining molecular mechanisms of GC is of vital significance. Here, we identified a novel oncogene WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) in GC. WWP1 could promote GC cell proliferation and migration in vitro and expedite GC growth in vivo. We also found out two microRNAs (miRNAs): miR‐129‐5p and ‐3p could both target WWP1. Interestingly, miR‐129‐5p bound to the CDS region of WWP1 mRNA. The miR‐129 pairs (miR‐129‐5p and ‐3p) play pivotal roles in GC to suppress its proliferation and migration in vitro and slow down GC growth in vivo by repressing WWP1. In summary, we identified two tumor suppressive miRNAs which share the same precursor that could regulate the same oncogene WWP1 in GC. Our finding would add new route for GC research and treatment.
Mechanically stimulated osteocytes reduce the bone‐metastatic potential of breast cancer cells in vitro by signaling through endothelial cells
Authors: Ma Yu‐Heng Vivian , Xu Liangcheng , Mei Xueting , Middleton Kevin , You Lidan 
Published: November 2018

AbstractBone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. In this study, we investigated the specific effects of flow‐stimulated osteocytes on the interaction between endothelial cells and breast cancer cells in vitro. We observed that CM from flow‐stimulated osteocytes reduced endothelial permeability by 15% and breast cancer cell adhesion onto endothelial monolayers by 18%. The difference in adhesion was abolished with anti‐intercellular adhesion molecule 1 (ICAM‐1) neutralizing antibodies. Furthermore, CM from endothelial cells conditioned in CM from flow‐stimulated osteocytes significantly altered the gene expression in bone‐metastatic breast cancer cells, as shown by RNA sequencing. Specifically, breast cancer cell expression of matrix metallopeptidase 9 (MMP‐9) was downregulated by 62%, and frizzled‐4 (FZD4) by 61%, when the osteocytes were stimulated with flow. The invasion of these breast cancer cells across Matrigel was also reduced by 47%, and this difference was abolished by MMP‐9 inhibitors. In conclusion, we demonstrated that flow‐stimulated osteocytes downregulate the bone‐metastatic potential of breast cancer cells by signaling through endothelial cells. This provides insights into the capability of bone mechanical regulation in preventing bone metastases; and may assist in prescribing exercise or bone‐loading regimens to patients with breast cancers.
The role of DEAD‐box RNA helicase p68 (DDX5) in the development and treatment of breast cancer
Authors: Hashemi Vida , Masjedi Ali , Hazhir‐karzar Bita , Tanomand Asghar , Shotorbani Siamak Sandoghchian , Hojjat‐Farsangi Mohammad , Ghalamfarsa Ghasem , Azizi Gholamreza , Anvari Enayat , Baradaran Behzad , Jadidi‐Niaragh Farhad 
Published: November 2018

AbstractRNA helicase p68 or DEAD (Asp‐Glu‐Ala‐Asp) box polypeptide 5 (DDX5) is a unique member of the highly conserved protein family, which is involved in a broad spectrum of biological processes, including transcription, translation, precursor messenger RNA processing or alternative splicing, and microRNA (miRNA) processing. It has been shown that p68 is necessary for cell growth and participates in the early development and maturation of some organs. Interestingly, p68 is a transcriptional coactivator of numerous oncogenic transcription factors, including nuclear factor‐κβ (NF‐κβ), estrogen receptor α (ERα), β‐catenin, androgen receptor, Notch transcriptional activation complex, p53 and signal transducer, and activator of transcription 3 (STAT3). Recent studies on the role of p68 (DDX5) in multiple dysregulated cellular processes in various cancers and its abnormal expression indicate the importance of this factor in tumor development. Discussion of the precise role of p68 in cancer is complex and depends on the cellular microenvironment and interacting factors. In terms of the deregulated expression of p68 in breast cancer and the high prevalence of this cancer among women, it can be informative to review the precise function of this factor in the breast cancer. Therefore, an attempt will be made in this review to clarify the tumorigenic function of p68 in association with its targeting potential for the treatment of breast cancer.
Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells
Authors: Zhang Li‐Na , Kong Chen‐Fei , Zhao Dan , Cong Xian‐Ling , Wang Shen‐Sen , Ma Ling , Huang Ying‐Hui 
Published: November 2018

AbstractCell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP‐2 and MMP‐9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0/G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial‐mesenchymal transition (EMT) change with downregulation of E‐cadherin and upregulation of N‐cadherin, Vimentin, α‐SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell‐like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.
MiRNAs and inflammatory bowel disease: An interesting new story
Authors: Moein Soheila , Vaghari‐Tabari Mostafa , Qujeq Durdi , Majidinia Maryam , Nabavi Seyed Mohammad , Yousefi Bahman 
Published: November 2018

AbstractInflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.
Osteoblast autophagy in glucocorticoid‐induced osteoporosis
Authors: Wang Lufei , Heckmann Bradlee L. , Yang Xianrui , Long Hu 
Published: November 2018

AbstractAdministration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid‐induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.
Understanding molecular biology of codon usage in mitochondrial complex IV genes of electron transport system: Relevance to mitochondrial diseases
Authors: Uddin Arif , Mazumder Tarikul Huda , Chakraborty Supriyo 
Published: November 2018

AbstractThe mitochondrial cytochrome oxidase (CO) genes are involved in complex IV of the electron transport system, and dysfunction of CO genes leads to several diseases. However, no work has been reported on the codon usage pattern of these genes. We used bioinformatic methods to analyze the compositional properties and the codon usage pattern of the COI, COII, and COIII genes in fishes, birds, and mammals to understand the similarities and dissimilarities of codon usage in these genes, which gave an insight into the molecular biology of these genes. The effective number of codons (ENC) value of genes was high in different species of fishes, birds and mammals, which indicates that the codon bias of CO genes was low and the ENC values were significantly different among fishes, birds, and mammals, as revealed from the t test. The overall guanine and cytosine (GC) content in fishes, birds, and mammals was lower than 50% in all genes, indicating that the genes were AT‐rich and significantly different among fishes, birds, and mammals. The TCA codon was overrepresented in fishes, birds, and mammals for the COI gene, in birds and mammals for the COII gene, but it was not overrepresented in others. Only three codons, namely CTA, CGA, and AAA, were overrepresented in all three groups for the COI, COII, and COIII genes, repectively. From the neutrality plot in fishes, birds, and mammals, it was observed that the slopes of the regression lines (regression coefficients) in the COI, COII, and COIII genes were <0.5, suggesting that natural selection played a major role, whereas mutation pressure played a minor role.
Extended proliferation of chicken‐ and Okinawa rail‐derived fibroblasts by expression of cell cycle regulators
Authors: Katayama Masafumi , Kiyono Tohru , Ohmaki Hitomi , Eitsuka Takahiro , Endoh Daiji , Inoue‐Murayama Miho , Nakajima Nobuyoshi , Onuma Manabu , Fukuda Tomokazu 
Published: November 2018

AbstractAlthough immortalized cultured cells are useful for various functional assays or transcriptome analysis, highly efficient and reproducible immortalization methods have not been developed in avian‐derived cells. We introduced the simian virus 40 T antigen (SV40T) and human papillomavirus
(HPV)‐E6E7 to chick and Okinawa rail (endangered species)derived fibroblast. As a result, neither the
SV40T nor
E6E7 genes could induce avian cell immortality. Accordingly, we attempted to use a recently developed immortalization method, which involved the coexpression of mutant cyclin‐dependent kinase 4 (CDK4), Cyclin D, and TERT (K4DT method) in these avian cells. Although the K4DT method could not efficiently induce the efficient immortalization in mass cell population, cellular division until the senescence was significantly extended by K4DT, we succeeded to obtain the immortalized avian cells (chick K4DT: one clone, Okinawa rail K4DT: three clones, Okinawa rail K4DT + telomerase RNA component: one clone) with K4DT expression. We conclude that K4DT expression is used to extend the cell division and immortalization of avian‐derived cells.
Interleukin‐18 and diabetic nephropathy: A review
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein 
Published: November 2018

AbstractThe inflammatory response has an important role in the pathophysiology of diabetic nephropathy that is contributed to by inflammatory mediators such as interleukin‐1 (IL‐1), IL‐6, IL‐18, tumor necrosis factor‐α, and macrophage chemotactic protein‐1; however, the role of IL‐18 seems to be more specific than other cytokines in the inflammatory process. IL‐18 is expressed in renal tissue and is upregulated by several stimuli including hyperglycemia. The expression/urinary level of IL‐18 is positively correlated with the progression of diabetic nephropathy and the urinary albumin excretion rate. In this review, we have focused on the molecular pathways modulating the relationship between IL‐18 and diabetic nephropathy.
MicroRNAs and signaling networks involved in epithelial–mesenchymal transition
Authors: Musavi Shenas Mohammad Hossein , Eghbal‐Fard Shadi , Mehrisofiani Vahid , Abd Yazdani Nima , Rahbar Farzam Omid , Marofi Faroogh , Yousefi Mehdi 
Published: November 2018

AbstractEpithelial–mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose their cell‐to‐cell connection and are detached from the base membrane. EMT is fundamental for many biological processes such as embryonic development and neurogenesis. It also plays a significant role in cancer progression and metastasis. EMT regulation occurs through a sophisticated network of transcription regulations that include many signaling pathways. The exact mechanism of cancer gene regulation has not been understood yet. However, it is interesting to study the role of microRNAs and epigenetics mechanism in the cancer development. In this review, the transcription regulation of EMT and the analysis of possible overlap between microRNAs and their targets which are involved in the cancer development are scrutinized.
Serenoa repens and N‐acetyl glucosamine/milk proteins complex differentially affect the paracrine communication between endothelial and follicle dermal papilla cells
Authors: Bassino Eleonora , Gasparri Franco , Munaron Luca 
Published: November 2018

AbstractCurrent treatments for hair follicle (HF) disruption are based on 5‐α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens (
SR) and
N‐acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both
SR and NAG/Lac‐induced endothelial tubulogenesis were enhanced by FDPC.
SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by
SR, was further augmented by FDPC. In FDPC 5‐α reductase‐II and β‐catenin expressions were modified by
SR and less by NAG/Lac, with no additional effect by HMVEC.
SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1β production. Finally,
SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.
miR‐124 promotes neural differentiation in mouse bulge stem cells by repressing Ptbp1 and Sox9
Authors: Mokabber Haleh , Najafzadeh Nowruz , Mohammadzadeh Vardin Mohammad 
Published: November 2018

AbstractHair follicle stem cells (HFSCs) are able to differentiate into neurons and glial cells. Distinct microRNAs (miRNAs) regulate the proliferation and differentiation of HFSCs. However, the exact role of miR‐124 in the neural differentiation of HFSCs has not been elucidated. HFSCs were isolated from mouse whisker follicles. miR‐9, let‐7b, and miR‐124, Ptbp1 , and Sox9 expression levels were detected by real‐time polymerase chain reaction (RT‐PCR). The influence of miR‐124 transfection was evaluated using immunostaining. We demonstrated that miR‐124 and let‐7b expression levels were significantly increased after the neural differentiation. Sox9 and Ptbp1 were identified as the target of miR‐124 in the HFSCs. During neural differentiation and miR‐124 mimicking, Ptbp1 and Sox9 levels were decreased. Moreover, the miR‐124 overexpression increased MAP2 (58.43 ± 11.26) and NeuN (48.34 ± 11.15) proteins expression. The results demonstrated that miR‐124 may promote the differentiation of HFSCs into neuronal cells by targeting Sox9 and Ptbp1.
Noncoding transcribed ultraconserved region (T‐UCR) UC.48+ is a novel regulator of high‐fat diet induced myocardial ischemia/reperfusion injury
Authors: Ding Lu , Gong Chengxin , Zhao Jiani , Liu Xingzi , Li Tao , Rao Shenqiang , Wang Shuo , Liu Yuanyuan , Peng Shanping , Xiao Wen , Xiong Chaopeng , Wang Rumeng , Liang Shangdong , Xu Hong 
Published: November 2018

AbstractIncreasing evidence has suggested high‐fat diet (HFD) is an independent risk factor for myocardial ischemia/reperfusion (MI/R) injury. Long noncoding RNAs (lncRNAs) recently attracted much attraction in the study of MI/R injury. However, the functional questions of specific lncRNAs in HFD‐induced MI/R injury have not been well elucidated. Uc.48+ is a lncRNA from a transcribed ultraconserved region (T‐UCR) of human, mouse, and rat genomes. Here, we explored the aggravating role of uc.48+and identified purinergic P2X7 receptor (P2X7R) as a downstream regulator of uc.48+ in HFD‐induced MI/R vulnerability. We demonstrated uc.48+ expression was upregulated, accompanied by the corresponding upregulation of P2X7R in HFD I/R myocardium and HFD‐induced MI/R vulnerability. Overexpression of uc.48+enhanced, whereas silencing of uc.48 + decreased the expression of P2X7R, cardiomyocyte apoptosis, and MI/R injury. The functional relevance of uc.48+ regulated P2X7R expression and the subsequent NF‐κB signaling to promote cardiomyocyte apoptosis was supported by inhibition of P2X7R with its specific antagonist (A438079) as well as the inhibitor of NF‐κB signaling (pyrrolidine dithiocarbamate, PDTC) in H9c2 hypoxia/reoxygenation (H/R) cells transfected with pcDNA3.0‐uc.48 + plasmid, and RNA immunoprecipitation (RIP) suggested uc.48+ could interact with transcription factor Sp1. Importantly, Sp1 inhibitor (mithramycin, MIT) was found to suppress uc.48+ ‐induced P2X7R expression and the NF‐κB signaling and cardiomyocyte apoptosis. Our findings provide a potential novel mechanism through which uc.48+ boosts cardiomyocyte apoptosis and MI/R vulnerability to HFD. Thus, uc.48+ is a novel regulator of HFD‐induced MI/R injury; targeting uc.48+ may be a novel therapeutic approach of MI/R vulnerability to HFD.
Sulfonyl(thio)urea derivative induction of insulin secretion is mediated by potassium, calcium, and sodium channel signal transduction
Authors: Sulis Paola Miranda , Dambrós Betina Fernanda , Mascarello Alessandra , dos Santos Adair Roberto Soares , Yunes Rosendo Augusto , Nunes Ricardo José , Frederico Marisa Jádna Silva , Barreto Silva Fátima Regina Mena 
Published: November 2018

AbstractAimTo investigate the mechanism of action of sulfonyl(thio)urea derivative (SD) on glycemia and on insulin secretion in pancreatic islets.MethodsWistar rats were divided into hyperglycemic control group, rats received 4 g/kg body weight glucose plus sitagliptin 10 mg/kg (p.o.); hyperglycemic plus SD 10 mg/kg (p.o.); hyperglycemic plus SD plus sitagliptin. Blood was collected before glucose overloading (zero time), and at 15, 30, 60, and 180 min after glucose, from the afore mentioned groups for glycemia and glucagon‐like peptide 1 (GLP‐1) measurements and intestinal disaccharidases activity. Pancreatic islets were isolated for the calcium influx and insulin secretion in in vitro studies.ResultsSD reduced glycemia and increased GLP‐1 secretion, while inhibited sucrase and lactase activity. This SD (1.0 and 10.0 µM) stimulated calcium influx in a similar percentile to that of glibenclamide, and in a nonsynergic manner. In addition, the trigger effect of SD on calcium influx was through the K+‐ATP‐dependent channels, and partially by activating voltage‐dependent K
+ channels and voltage‐dependent calcium channels. Furthermore, SD‐stimulated Na
+ and Ca
2+ entry, induced by the transient receptor potential ankyrin 1 and by modulation of Na
+/Ca
2+ exchange. The activation of these pathways by SD culminated in in vitro insulin secretion, reinforcing the critical role of K
+‐ATP channels in the secretagogue effect of SD.ConclusionsSD diminish glycemia by inducing GLP‐1 secretion and inhibiting disaccharidases. To our knowledge, this is the first report of an insulin secretagogue effect of SD that is mediated by potassium and calcium, as well as sodium, signal transduction.
Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media
Authors: Atrabi Mohammad Jafari , Akbarinejad Vahid , Khanbabaee Ramazan , Dalman Azam , Amorim Christiani Andrade , Najar‐Asl Mustafa , Valojerdi Mojtaba Rezazadeh , Fathi Rouhollah 
Published: November 2018

AbstractFertility preservation of prepubertal girls subjected to invasive cancer therapy necessitates defining protocols for activation of isolated primordial follicles. Granulosa (GCs) and cumulus cells (CCs) play pivotal role in oocyte development. Although GCs and CCs share some similarities, they differ in growth factors production. The current study was conducted to evaluate the effects of GCs, CCs and their conditioned media on mice primordial follicles activation. One‐day‐old mice ovaries were subjected to 6‐day culture with base medium (BM), GC conditioned medium (GCCM), GC coculture (GCCC), CC conditioned medium (CCCM) or CC coculture (CCCC). Follicular growth and primordial to primary follicle transition was observed during 6‐day culture, and follicular activation rate tended to be greater in GCCM than other groups (0.05 <P < 0.10). On Day 6, the expression of phosphatase and tensin homolog (PTEN) in GCCM group was lower than that in BM group (P = 0.020), the expression of phosphoinositide‐3‐kinase was higher in CCCC group than BM, GCCM and CCCM groups (P < 0.05), and the expression of connexin 37 was greater in the CCCM group as compared with BM, GCCC, and CCCC groups (P < 0.01). In conclusion, the current study showed that condition medium of GCs could enhance in vitro activation of primordial follicles, probably through downregulation of PTEN.