bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small‐molecule–based generation of functional cardiomyocytes from human umbilical cord–derived induced pluripotent stem cells
Authors: Wu Kai Hong , Wang Su Yun , Xiao Qian Ru , Yang Yu , Huang Ning Ping , Mo Xu Ming , Sun Jian 
Published: October 2018

AbstractThe purpose of this study was to investigate the cardiac‐differentiation potential of induced pluripotent stem cells (iPSCs) generated from human umbilical cord–derived mesenchymal cells. Spontaneous beating colonies were observed at day 7 after the sequential addition of CHIR99021 and IWP‐4. The combined use of CHIR99021 and IWP‐4 downregulated the expression of pluripotency markers while upregulating cardiac transcription factors and cardiomyocyte‐specific markers. The derived cardiomyocytes demonstrated typical sarcomeric structures and action‐potential features; most importantly, the derived cells exhibited responsiveness to β‐adrenergic and muscarinic stimulations. The analyses of molecular, structural, and functional properties revealed that the derived cardiomyocytes were similar to cardiomyocytes derived from BJ foreskin fibroblast cells. In summary, our results demonstrate that functional cardiomyocytes can be generated from human umbilical cord–derived cells. The methodology described here has potential as a means for the production of functional cardiomyocytes from discarded human umbilical cord tissue.
Phospholipase C‐γ2 promotes intracellular survival of mycobacteria
Authors: Paroha Ruchi , Chaurasiya Shivendra K. , Chourasia Rashmi 
Published: October 2018

AbstractMycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not
Mycobacterium smegmatis (MS) induces phosphorylation of PLC‐γ2 at tyrosine 1217 in J774A.1 cells. Small interfering RNA–mediated knockdown of PLC‐γ2 expression leads to the enhanced killing of both MS and Mtb by these cells suggesting that Mtb activates PLC‐γ2 to promote its intracellular survival within macrophages. Knockdown of PLC‐γ2 also lead to increased uptake of Mtb but not MS by J774.A.1 cells. Further, we have observed that PLC‐γ2 was required for Mtb‐induced inhibition of expression of proinflammatory cytokine tumor necrosis factor‐α, inducible nitric oxide synthase, and chemokine (C‐C motif) ligand 5 (RANTES). Altogether, our results for the first time demonstrate that Mtb induces activation of macrophages PLC‐γ2 to inhibit their mycobactericidal response.
Ubiquitin‐proteasome system and ER stress in the brain of diabetic rats
Authors: Shruthi Karnam , Reddy S Sreenivasa , Chitra P Swathi , Reddy G Bhanuprakash 
Published: October 2018

AbstractThe ubiquitin‐proteasome system (UPS) has been implicated in the pathogenesis of many neurodegenerative diseases. Endoplasmic reticulum (ER) stress is shown to play a pathological role in the development of diabetes and its complications. Hence, the current study is aimed to investigate the role of UPS and ER stress in the cerebral cortex of diabetic rats and examine the therapeutic effect of 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor. Male Sprague‐Dawley rats were divided into three groups: control, diabetes, and diabetes plus 4‐PBA treatment group. Diabetes was induced by single intraperitoneal streptozotocin injection (37 mg/kg body weight [bw]), and 4‐PBA was administered (40 mg/kg bw/d, intraperitoneal) for 2 months, starting from 2 months of diabetes induction. At the end of 4 months, cerebral cortex was collected for analysis. Declined proteasome activity and ubiquitin C‐terminal hydrolase (UCH)‐L1 expression, increased ubiquitinated proteins, and apoptosis were observed in the diabetic rats. The expression of the ubiquitin‐activating enzyme E1, UCHL5, and ER stress markers (ATF6, pPERK, and CHOP) was markedly elevated, whereas the expression of ER‐associated protein degradation (ERAD) components was downregulated in the diabetic rats. 4‐PBA intervention attenuated ER stress, alterations in UPS, and ERAD components in diabetic rats. Importantly, neuronal apoptosis was lowered in 4‐PBA‐treated diabetic rats. Our observations demonstrate that altered UPS could be one of the underlying mechanisms of neuronal apoptosis in diabetes and chemical chaperones such as 4‐PBA could be potential candidates for preventing these alterations under hyperglycemic conditions.
The competing endogenous circular RNA ADAMTS14 suppressed hepatocellular carcinoma progression through regulating microRNA‐572/regulator of calcineurin 1
Authors: Song Changlong , Li Dianqiu , Liu Hongyu , Sun Hongyan , Liu Zhen , Zhang Lirong , Hu Yu 
Published: October 2018

AbstractEmerging evidence have discovered that circular RNAs (circRNAs) may serve as diagnostic or tumor promising biomarkers. This study aimed to investigate how circular RNA ADAMTS14 (circADAMTS14) regulates microRNA‐572/
regulator of calcineurin 1(miR‐572/
RCAN1) in hepatocellular carcinoma (HCC). The expression profiles of circRNA/microRNA (mRNA) between HCC tissues and paired adjacent tissues were analyzed via microarray analysis. The expressions of circADAMTS14, miR‐572, and
RCAN1 were measured by real‐time polymerase chain reaction (PCR). The protein expression level of
RCAN1 in HCC cells was detected by western blot. The viability and apoptosis levels of HCC cell lines were measured by the cell counting Kit‐8 (CCK‐8) assay and fluorescence‐activated cell sorter. The invasiveness and migration of cells were detected based on the transwell and wound‐healing assay, respectively. The dual‐luciferase reporter assays were used to reveal circADAMTS14 and
RCAN1 as a potential target of miR‐572, which was predicted by TargetScan and miRBase. The effect of circADAMTS14 on HCC cells was demonstrated by tumor formation in nude mice in vivo. CircADAMTS14 and
RCAN1 were lowly expressed in HCC clinical specimens and cell lines using microarrays and qRT‐PCR, but miR‐572 inversely. Our study further verified the direct interaction between circADAMTS14 and
RCAN1 with miR‐572 via the dual‐luciferase reporter gene assay. Overexpressed circADAMTS14 and
RCAN1 induced apoptosis of HCC cells and inhibited cell proliferation and invasion. But overexpressed miR‐572 could decrease apoptosis of HCC cells and promote proliferation and invasion. In vivo, circADAMTS14 inhibited the tumor growth, correlated positively with the protein expression levels of
RCAN1. Our results demonstrated that circADAMTS14 might suppress HCC progression through regulating miR‐572/
RCAN1 as the competing endogenous RNA.
Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance
Authors: Mihanfar Aynaz , Aghazadeh Attari Javad , Mohebbi Iraj , Majidinia Maryam , Kaviani Mojtaba , Yousefi Mehdi , Yousefi Bahman 
Published: October 2018

AbstractThe cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV‐CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC‐mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer.
Arsenic trioxide inhibits the differentiation of fibroblasts to myofibroblasts through nuclear factor erythroid 2‐like 2 (NFE2L2) protein and the Smad2/3 pathway
Authors: Zhong Lingzhi , Hao Haojie , Chen Deyun , Hou Qian , Zhu Ziying , He Wenjun , Sun Sujing , Sun Mengli , Li Meirong , Fu Xiaobing 
Published: October 2018

BackgroundTissue contraction and the extracellular matrix deposition are part of the pathogenesis of hypertrophic scars. The transcriptional factor NFE2L2 inhibits fibroblast differentiation in idiopathic pulmonary fibrosis and promotes myofibroblast dedifferentiation. Our previous study showed that the transcription factor NFE2L2 was strongly induced on treatment with arsenic trioxide (ATO).ObjectiveThe present study sought to investigate the effect of ATO on myofibroblast formation to determine its potential role in hypertrophic scar treatment.MethodsSmall interfering RNA against NFE2L2 was used on treatment with ATO in human skin myofibroblasts. The expression levels of fibrosis markers were assessed by reverse transcription polymerase chain reaction, western blot, and immunofluorescence staining. The transforming growth factor‐β1 (TGF‐β1)/Smad2/3 signaling was detected by western blot. A rabbit ear model was used to evaluate the antifibrotic role of ATO.ResultsAt the cellular level, ATO abolished fibroblast differentiation in response to TGF‐β1. ATO reduced TGF‐β1‐induced reactive oxygen species accumulation through increased expression of the antioxidant gene HO‐1 in fibroblasts. In addition, ATO promoted the nuclear translocation of NFE2L2 and inhibited the phosphorylation of Smad2/3. In the rabbit ear model, ATO prevented the progression of hypertrophic scar formation.ConclusionsThis study provides the first evidence implying that ATO inhibits the formation of myofibroblasts in vivo and in vitro and provides a possible treatment for hypertrophic scars.
LncRNA882 regulates leukemia inhibitory factor (LIF) by sponging miR‐15b in the endometrial epithelium cells of dairy goat
Authors: Zhang Lei , Liu Xiaorui , Cui Jiuzeng , Che Sicheng , Liu Yuexia , An Xiaopeng , Cao Binyun , Song Yuxuan 
Published: October 2018

AbstractDespite the fact that long noncoding RNAs (lncRNAs) play roles in almost all biological processes, little is known about their biological function in the endometrium during the formation of endometrial receptivity. In this study, a comprehensive analysis of lncRNAs in goat endometrial tissues on Day 5 (prereceptive endometrium, PE) and Day 15 (receptive endometrium, RE) of pregnancy was performed by using RNA‐Seq. As a result, 668 differentially expressed lncRNAs (DELs) were found between the PE and RE. Further study showed that lncRNA882, regulated by estrogen (E2) and progestin (P4), could act as competing endogenous RNAs (ceRNAs) for miR‐15b, which inhibited the expression of transforming growth factor‐b‐activated kinase 1 binding protein 3 (TAB3) and then indirectly regulated the level of leukemia inhibitory factor (LIF). This was helpful for the formation of endometrial receptivity in dairy goats. In conclusion, we elucidated the endometrium lncRNA profiles of PE and RE in dairy goats; lncRNA882 acted as a ceRNA for miR‐15b and then indirectly regulated the level of LIF in goat endometrial epithelium cells. Thus, this study helped us to better understand the molecular regulation of endometrial receptivity in dairy goats.
Protein malnutrition mitigates the effects of a high‐fat diet on glucose homeostasis in mice
Authors: Branco Renato Chaves Souto , Camargo Rafael Ludemann ,  Batista Thiago Martins , Vettorazzi Jean Franciesco , Lubaczeuski Camila , Bomfim Lucas Henrique Montes , Silveira Leonardo Reis , Boschero Antônio Carlos , Zoppi Cláudio Cesar , Carneiro Everardo Magalhães 
Published: October 2018

AbstractNutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high‐fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein‐restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein‐control diet) or a protein‐restricted (6% protein‐restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein‐restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome‐proliferator‐activated receptor gamma coactivator 1‐alpha protein content, and higher levels of malate and α‐ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc‐dependent kinase and acetyl coenzyme‐A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl‐CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.
Resveratrol restores sensitivity of glioma cells to temozolamide through inhibiting the activation of Wnt signaling pathway
Authors: Yang Hua‐Chao , Wang Jun‐Yi , Bu Xing‐Yao , Yang Bin , Wang Bang‐Qing , Hu Sen , Yan Zhao‐Yue , Gao Yu‐Shuai , Han Shuang‐Yin , Qu Ming‐Qi 
Published: October 2018

AbstractMalignant gliomas are aggressive primary neoplasms that originate in the glial cells of the brain or the spine with notable resistance to standard treatment options. We carried out the study with the aim to shed light on the sensitization of resveratrol to temozolomide (TMZ) against glioma through the Wnt signaling pathway. Initially, glioma cell lines with strong resistance to TMZ were selected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Then, the glioma cells were subjected to resveratrol, TMZ, Wnt signaling pathway inhibitors, and activators. Cell survival rate and inhibitory concentration at half maximum value were detected by MTT, apoptosis by flow cytometry, and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining, in vitro proliferation by hanging drop method and β‐catenin translocation into nuclei by TOP/FOP‐FLASH assay. The expressions of the Wnt signaling pathway‐related and apoptosis‐related factors were determined by western blot analysis. Nude mice with glioma xenograft were established to detect tumorigenic ability. Glioma cell lines T98G and U138 which were highly resistant to TMZ were selected for subsequent experiments. Resveratrol increased the efficacy of TMZ by restraining cell proliferation, tumor growth, and promoting cell apoptosis in glioma cells. Resveratrol inhibited Wnt2 and β‐catenin expressions yet elevated GSK‐3β expression. Moreover, the Wnt signaling pathway participates in the sensitivity enhancing of resveratrol to TMZ via regulating
O
6‐methylguanine‐DNA methyltransferase (MGMT) expression. Resveratrol sensitized TMZ‐induced glioma cell apoptosis by repressing the activation of the Wnt signaling pathway and downregulating MGMT expression, which may confer new thoughts to the chemotherapy of glioma.
Chromatin‐regulatory genes served as potential therapeutic targets for patients with urothelial bladder carcinoma
Authors: Qiu Jian‐Guo , Shi Da‐Yan , Liu Xin , Zheng Xi‐Xia , Wang Lei , Li Qian 
Published: October 2018

AbstractUrothelial bladder carcinoma is the ninth most common cancer in the world, with an estimated 150,000 deaths per year. Two comprehensive analysis based on The Cancer Genome Atlas urothelial bladder carcinoma reported that chromatin modifier gene mutations were common in bladder cancer. We aimed to find how the mutations and transcriptional profiles of the genes involving in chromatin modification affected the prognosis of patients. The data were retrieved from the Genomic Data Commons data portal and the gene list in pathway Chromatin Modifying Enzymes were obtained from Reactome. The expression levels and mutational profiles of the genes involving in the chromatin were utilized altogether to construct a fusion patient similarity network by similarity network fusion. The genes that were differentially expressed in one clustered group or two were identified. Fifty chromatin‐regulating genes had nonsilent mutations in at least 10 patients. KMT2D, KDM6A, CREBBP, ARID1A, and ARID2 had enriched inactivating mutations. Among 399 cases where both the single‐nucleotide polymorphism information and the messenger RNA expression profiles were available, 326, 23, and 50 patients were clustered into Groups 1, 2, and 3, respectively. The survival analysis suggested that the patients in these three groups had a different prognosis. Thity‐one genes were identified as differentially expressed in any group. The Gene Ontology term enrichment showed that the differentially expressed genes were enriched in the immune response especially in the complement activation. Altogether, chromatin‐regulatory genes were key in bladder cancer and can serve, with the differentially expressed genes, as potential therapeutic targets.
Retracted: Effects of microRNA‐370 on mesangial cell proliferation and extracellular matrix accumulation by binding to canopy 1 in a rat model of diabetic nephropathy
Authors: Yu Feng‐Na , Hu Ming‐Lan , Wang Xin‐Fang , Li Xiang‐Ping , Zhang Bei‐Hao , Lu Xiao‐Qing , Wang Rui‐Qiang 
Published: October 2018

AbstractAs one major diabetic complication, diabetic nephropathy (DN) has been reported to be associated with various kinds of microRNA (miRNA). Thus, we conducted this study to explore the potential of miR‐370 in a rat model of DN through investigation of mesangial cell proliferation and extracellular matrix (ECM). A total of 40 healthy adult male Sprague–Dawley rats were enrolled and assigned into normal (n = 10) and DN (
n = 30, DN rat model) groups. Dual‐luciferase reporter assay was performed for the targeting relationship between miR‐370 and canopy 1 (CNPY1). Mesangial cells were collected and transfected with prepared mimic, inhibitor or small interfering RNA (siRNA) for analyzing the effect of miR‐370 on DN mice with the help of expression and cell biological processes detection. CNPY1 was confirmed as a target gene of miR‐370. DN mice had increased expression of miR‐370, fibronectin, type I collagen (Col I), type IV collagen (Col IV), and plasminogen activator inhibitor‐1 (PAI‐1) but reduced CNPY1 expression. Cells transfected with miR‐370 mimic and siRNA–CNPY1 had increased expression of fibronectin, Col I, Col IV, and PAI‐1 but decreased CNPY1 expression. The miR‐370 mimic and siRNA–CNPY1 groups showed increased cell proliferation, as well as elevated ECM accumulation and declined cell apoptosis rate as compared with the blank and negative control groups, with reverse trends observed in the miR‐370 inhibitor group. Our study concludes that overexpression of miR‐370 promotes mesangial cell proliferation and ECM accumulation by suppressing CNPY1 in a rat model of DN.
LINC00707 promotes hepatocellular carcinoma progression through activating ERK/JNK/AKT pathway signaling pathway
Authors: Wang Jianchu , Luo Zongjiang , Yao Tianwei , Li Wenchuan , Pu Jian 
Published: October 2018

AbstractIncreasing evidence has demonstrated that abnormal expression of lncRNA is correlated with various malignant tumors, including hepatocellular carcinoma (HCC). Our current study was aimed to investigate the role of LINC00707 in HCC development. We observed that LINC00707 was upregulated in HCC cell lines compared with normal liver cell lines. Then, Hep3B cells and SNU449 cells were infected with LV‐shLINC00707 and LV‐LINC00707. LINC00707 silencing could greatly repress the proliferation and colony formation of HCC cells in vitro. On the contrary, overexpression of LINC00707 induced HCC cell proliferation and colony formation. In addition, HCC cell apoptosis was significantly enhanced and HCC cell cycle was blocked in G1 phase by LV‐shLINC00707. Hep3B cells and SNU449 cell invasion capacity was restrained by the knockdown of LINC00707, whereas upregulation of LINC00707 exhibited an opposite phenomenon. Accumulating evidence has reported that ERK/JNK/AKT signaling is involved in multiple cancers, including HCC. Here, in our study, we identified that ERK/JNK/AKT signaling was dramatically restrained by silencing of LINC00707 while activated by LV‐LINC00707 in HCC cells. Subsequently, an in vivo experiment was conducted, and it demonstrated that LINC00707 could modulate HCC development through activating ERK/JNK/AKT signaling. Taking the above results together, it was implied in our study that LINC00707 contributed to HCC progression through modulating the ERK/JNK/AKT pathway.
RNA‐binding protein, human antigen R regulates hypoxia‐induced autophagy by targeting ATG7/ATG16L1 expressions and autophagosome formation
Authors: Palanisamy Kalaiselvi , Tsai Tsung‐Hsun , Yu Tung‐Min , Sun Kuo‐Ting , Yu Shao‐Hua , Lin Feng‐Yen , Wang I‐Kuan , Li Chi‐Yuan 
Published: October 2018

AbstractAutophagy, a prosurvival mechanism offers a protective role during acute kidney injury. We show novel findings on the functional role of RNA binding protein, HuR during hypoxia‐induced autophagy in renal proximal tubular cells‐2 (HK‐2). HK‐2 cells showed upregulated expressions of HuR and autophagy‐related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin‐RNA‐mediated loss of HuR function in HK‐2 cells significantly decreased ATG7 and ATG16L1 protein expressions. Bioinformatics prediction revealed HuR motif binding on the coding region of ATG7 and AU‐rich element at 3′UTR ATG16L1 messnger RNA (mRNA). The RNA immunoprecipitation study showed that HuR was predominantly associated with ATG7 and ATG16L1 mRNAs under hypoxia. In addition, HuR enhanced autophagosome formation by regulating LC3II expressions. These results show that HuR regulates ATG7 and ATG16L1 expressions and thereby mediate autophagy in HK‐2 cells. Importantly, HuR knockdown cells underwent apoptosis during hypoxia as observed through the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Collectively, these findings show the crucial role of HuR under hypoxia by regulating autophagy and suppressing apoptosis in renal tubular cells.