bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between a functional variant at PTGS2 gene 3′UTR and its mRNA expression in lymphoblastoid cell lines
Authors: Wang Xueting , Zhao Yunzhao , Wang Yanru , Wang Zexing , Guan Xiaoxiang 
Published: August 2013

AbstractPTGS2 genetic 3′ untranslated region (3′UTR) miRNA binding sites variants are significantly associated with cancer risk; however, the roles of genetic variants in PTGS2 gene 3′UTR and post‐transcriptional regulation have not been elucidated. We report that rs689470 and rs5275 in the PTGS2 3′UTR have potential miRNA‐binding sites by using bioinformatics analysis. However, only the rs689470 was significantly associated with PTGS2 mRNA expression in lymphoblastoid cell lines (P = 0.026), but not for rs5275 (P = 0.626). rs689470 might be putative variants mediating the post‐transcriptional regulation of target PTGS2 gene. Better understanding of how 3′UTR variants regulate PTGS2 activity will pave the way to targeting the PTGS2 pathway in cancer therapy.
Direct TGF‐β1 signaling between activated platelets and pancreatic cancer cells primes cisplatin insensitivity
Authors: Chen Hongxu , Lan Xiang , Liu Menggang , Zhou Bo , Wang Baoling , Chen Ping 
Published: August 2013

AbstractThe exact mechanisms underlying chemotherapy insensitivity in pancreatic cancer remain largely unclear. The dynamic cross talk between tumors and their microenvironment is an important determinant of cancer chemosensitivity. However, whether additional signals provided during the intravascular transit of tumor cells affect the sensitivity of pancreatic cancer cells to chemotherapy is unknown. We have found that activated platelet–cancer cell interactions are sufficient to prime cisplatin (CDDP) insensitivity in pancreatic cancer cells. Activated platelet‐derived TGF‐β1 rather than direct platelet–tumor cell contacts stimulates PI3K/Akt and MEK/Erk signaling in pancreatic cancer cells, resulting in reduction of CDDP sensitivity in these cells. Therefore, the platelet–tumor cell interactions and the relevant signaling pathways that prime CDDP insensitivity may be potential targets for adjuvant chemotherapy for pancreatic cancer.
Inhibition of ATP‐induced calcium influx by homocysteine in human umbilical vein endothelial cells
Authors: Cortés Magdalena P. , Becerra Juan P. , Vinet Raúl , Álvarez Rocío , Quintana Irene 
Published: August 2013

AbstractMechanisms involved in the association between hyperhomocysteinemia and vascular occlusive diseases remain unclear. Homocysteine (Hcy) may disturb calcium (Ca2+) cytosolic regulation in endothelial cells, a process that can directly affect the synthesis of vasoactive substances, such as nitric oxide (NO). We have investigated the effect of acute and chronic incubation with high concentrations of Hcy (100 and 500 μmol/L) on the changes in the intracellular Ca2+ concentration ([Ca2+]i) induced by ATP, using primary cultures of human umbilical vein endothelial cells (HUVEC). The changes in [Ca2+]i, expressed as ΔFt/Fb, were measured using the microspectrofluorimetric technique with Fluo‐3 as Ca2+ indicator. HUVEC acutely exposed to Hcy did not produce significant effects on any of the parameters studied. However, chronic exposition (24 h) caused a significant decrease in the speed of store‐mediated Ca2+ entry, expressed as (ΔFt/Fb)/t (s−1). Exposure of HUVEC to 100 and 500 µmol/L Hcy gave significantly lower values (0.019 ± 0.002 s−1, n = 5 and 0.021 ± 0.004 s−1, n = 6, respectively) compared to the controls (0.046 ± 0.004 s−1, n = 8, P < 0.003). This was detected only when the sustained phase of the ATP‐induced [Ca+2]i increase was isolated. These results demonstrate that high concentrations of Hcy can affect the mechanisms involved in [Ca2+]i regulation of HUVEC, and that alteration occurs specifically in the sustained phase, which has been directly associated with NO synthesis.
Rho kinase pathway is likely responsible for the profibrotic actions of aldosterone in renal epithelial cells via inducing epithelial–mesenchymal transition and extracellular matrix excretion
Authors: Wei Jiali , Li Zhuori , Ma Chunyang , Zhan Feng , Wu Wei , Han Hui , Huang Yun , Li Wenning , Chen Daojun , Peng Youming 
Published: August 2013

AbstractIt has been demonstrated that aldosterone (ALD) plays a direct profibrotic role in the kidney but the underlying mechanism remains unclear. We examined the role of Rho kinase signal pathway in epithelial–mesenchymal transition (EMT) process and extracellular matirx (ECM) synthesis induced by ALD in human renal proximal tubular epithelial (HK‐2) cells in vitro. Rho kinase and collagen I, III protein expressions were detected by ELISA. E‐cadherin, α‐smooth muscle actin (SMA), collagen_I and collagen III mRNA expressions were detected by real time PCR. E‐cadherin, and α‐SMA protein expressions were measured by Western blot. Our results showed that ALD could significantly activate the Rho kinase in HK‐2 cells, while in the presence of mineralocorticoid receptor (MR) antagonist eplerenone and Rho kinase inhibitor Y27632, the Rho kinase protein expression were almost completely prevented. Exposure of HK‐2 cells to ALD for 48 h induced EMT as evidenced by loss of E‐cadherin, and de novo expression of α‐SMA. The EMT was completely blocked by eplerenone and Y27632. Meanwhile, ALD could significantly increase the mRNA and protein expressions of collagen I, III in HK‐2 cells when compared with the control group, while eplerenone and Y27632 could almost reverse these effects. These observations suggest that ALD can activate Rho kinase pathway and Rho kinase pathway is likely responsible for the profibrotic actions of ALD in renal proximal tubular epithelial cells via inducing EMT and ECM excretion.
Aberrant expression of microRNAs involved in epithelial–mesenchymal transition of HT‐29 cell line
Authors: Cai Zhi‐Gang , Zhang Shao‐Ming , Zhang Hang , Zhou Yi‐Yong , Wu Hai‐Bo , Xu Xiao‐Ping 
Published: August 2013

AbstractEpithelial–mesenchymal transition (EMT) is an essential step for cancer metastasis. MicroRNAs (miRNAs) are small non‐coding RNAs that regulate target‐mRNAs post‐transcriptionally. The expression and function of miRNAs in EMT of HT‐29 colonic cells remain elusive. This study looks at expression of miRNAs in EMT and explores the effects of miRNAs on EMT in HT‐29 cell line. HT‐29 was treated with TGF β to establish an EMT model, in which a collection of miRNAs was dynamically regulated by real‐time PCR (qPCR) analysis. Among them, miR‐21 and miR‐27 were significantly upregulated, while miR‐22, miR‐26, miR‐30, miR‐181, miR‐200b, miR‐200c and miR‐214 were markedly downregulated. MiRNA‐inhibitors were used to knockdown miRNAs in HT‐29 and EMT markers were determined by qPCR to monitor the effects of miRNAs on EMT process. Results showed that miR‐22 could not alter the expression of EMT markers, while knockdown of miR‐200b could significantly increase that of epithelial markers, N‐cadherin, Vimentin, α‐Sma and Twist1 and decrease that of mesenchymal marker, E‐cadherin. Bioinformatic analysis and Western blot showed that ZEB1 was directly suppressed by miR‐200b. In conclusion, miRNAs are dynamically regulated in TGF β‐induced EMT of HT‐29 and miR‐200b was essential for EMT by suppressing the expression of ZEB1 in HT‐29.
Canine mesenchymal stem cells (MSCs): characterization in relation to donor age and adipose tissue‐harvesting site
Authors: Guercio Annalisa , Di Bella Santina , Casella Stefania , Di Marco Patrizia , Russo Carmelo , Piccione Giuseppe 
Published: August 2013

AbstractAdipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources, for example it is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose‐derived mesenchymal stem cells (MSCs) yields a high amount of stem cells, essential for stem cell‐based therapies and tissue engineering. We have explored the effect of donor age, and the anatomical origin of the adipose tissue on several aspects of MSCs in dogs, such as cell yield, proliferative ability, multi‐differentiation potential, colony‐forming capacity, stemness marker expression. We also assessed the effect of cell passaging on the MSCs stemness. We found that the anatomical origin of the adipose tissue and the age of donors have effects only on the proliferative capacity of the MSCs. Moreover, cells show a progressive loss of the stemness characteristics with passages. Cell therapies need a suitable number of cells to use in clinical applications. Characterization of MSCs at different passages, allowed us to demonstrate that, under our culture conditions, the best quantitative and qualitative characteristics are obtained at early passages. Adult MSCs are of particular interest for the therapeutic approach to musculoskeletal diseases, and the dog provides an excellent preclinical model for the development of new approaches in regenerative medicine that might be applied to humans.
Histone H3 is absent from organelle nucleoids in BY‐2 cultured tobacco cells
Authors: Takusagawa Mari , Tamotsu Satoshi , Sakai Atsushi 
Published: August 2013

AbstractThe core histone proteins (H2A, H2B, H3 and H4) are nuclear‐localised proteins that play a central role in the formation of nucleosome structure. They have long been considered to be absent from extra‐nuclear, DNA‐containing organelles; that is plastids and mitochondria. Recently, however, the targeting of core histone H3 to mitochondria, and the presence of nucleosome‐like structures in mitochondrial nucleoids, were proposed in cauliflower and tobacco respectively. Thus, we examined whether histone H3 was present in plant organelles and participated in the organisation of nucleoid structure, using highly purified organelles and organelle nucleoids isolated from BY‐2 cultured tobacco cells. Immunofluorescence microscopic observations and Western blotting analyses demonstrated that histone H3 was absent from organelles and organelle nucleoids, consistent with the historical hypothesis. Thus, the organisation of organelle nucleoids, including putative nucleosome‐like repetitive structures, should be constructed and maintained without participation of histone H3.
Synaptic adhesion molecules in Cadm family at the neuromuscular junction
Authors: Tanabe Yuko , Fujita Eriko , Hayashi Yukiko K. , Zhu Xinran , Lubbert Hermann , Mezaki Yoshihiro , Senoo Haruki , Momoi Takashi 
Published: August 2013

AbstractRA175/SynCAM1/Cadm1 (Cadm1), a member of the immunoglobulin superfamily, is a synaptic cell adhesion molecule that has a PDZ‐binding motif at the C‐terminal region. It promotes the formation of presynaptic terminals and induces functional synapses in the central nervous system. Cadm1‐deficient (knockout [KO]) mice show behavioral abnormalities, including excessive aggression and anxiety, but do not show any symptoms of neuromuscular disorder, although neuromuscular junctions (NMJs) have structures similar to synapses. We have examined the expression of members of the Cadm family in the mouse muscle tissues. Cadm4 and Cadm1 were major components of the Cadm family, and Cadm3 was faintly detected, but Cadm2 was not detected by RT‐PCR. Cadm4 as well as Cadm1 colocalized with alpha‐bungarotoxin at the NMJs and interacted with the multiple PDZ domain protein Mupp1. Cadm4 was expressed in Cadm1‐KO mice and might compensate for Cadm1 loss through interactions with Mupp1.
Silencing Cofilin‐1 blocks PDGF‐induced proliferation in eutopic endometrium of endometriosis patients
Authors: Wang Dan‐Bo , Xu Yan‐Li , Chen Peng , Chen Ying‐Han , Li Yan 
Published: August 2013

AbstractPlatelet‐derived growth factor (PDGF) is well known to induce proliferation in variety of cells. The aim of this study was to investigate whether there is a correlation between the expression of Cofilin‐1 (CFL1) and the proliferation of eutopic endometrium stromal cells (ESC) in response to PDGF stimulation. Results show that PDGF induced the expression of CFL1 in ESC and promoted proliferation of ESC significantly in a time‐ or dose‐dependent manner. After silencing CFL1, the effect of PDGF on promoting ESC proliferation was significantly decreased. These data demonstrate that PDGF can induce CFL1 expression in ESC. Silencing CFL1 blocks PDGF‐induced proliferation in ESC.
Myocardial structural protein expression in umbilical cord blood mesenchymal stem cells after myogenic induction
Authors: Ma Nan , Ding Fangbao , Zhang Junwen , Bao Chunrong , Zhong Hong , Mei Ju 
Published: August 2013

AbstractTo assess the effects of three methods of inducing myogenic cells differentiation, umbilical blood mesenchymal stem cells (UCMSCs) from nearly full‐term pregnancy mongrel dogs were purified and cultured. Fourth‐passage UCMSCs were used to detect surface antigens, including CD11a, CD11b, CD29, CD34 and CD71. The cells were induced by 5‐azacytidine (5‐aza), myocardial lysates and myocardial induced fluid. Positive expression of Nkx2.5, α‐actin, desmin, β‐MHC and troponin‐I (TN I) were detected after 3 weeks. The immunohistochemical results were CD11a (−), CD11b (−), CD34 (−), CD29 (+) and CD71 (+). Nkx2.5 was detected in 5‐aza group, myocardial lysates group and myocardial induced fluid group. Semi‐quantitative analysis showed Nkx2.5 expression significantly higher in myocardial lysates group than in the 5‐aza group or myocardial‐induced fluid group (P < 0.05), but there was no significant difference between the 5‐aza and myocardial‐induced fluid groups for Nkx2.5 expression (P > 0.05). MSCs did not express myocardial structural proteins before differentiation, but α‐actin, desmin, β‐MHC and troponin‐I were present after differentiation. The positive expression of four proteins differed with the differentiation conditions. The UCMSCs can be differentiated into myogenic cells by three methods, but the degrees of differentiation are inconsistent. Our results show that the effects of 5‐aza and myocardial lysates are better than that of myocardial induced fluid.
Homage to Rita Levi‐Montalcini, the queen of modern neuroscience
Authors: Aloe Luigi , Chaldakov George N. 
Published: August 2013

AbstractThe first cell growth factor, nerve growth factor (NGF), was discovered by Rita Levi‐Montalcini (RLM) in the early 1950s. Originally identified as neurite outgrowth‐stimulating factor, later studies revealed that non‐neuronal cells, including immune cells, endothelial cells, cardiomyocytes, pancreatic beta cells, prostate epithelial and adipose tissue cells, were also targets for and/or sources of NGF. Nerve growth factor is well recognised as mediating multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other members of the neurotrophin family are implicated in the pathogenesis of a large spectrum of neuronal and non‐neuronal diseases, ranging from Alzheimer's and other neurodegenerative diseases to atherosclerosis and cardiometabolic disorders. Recent studies have demonstrated the therapeutic potentials of NGF in these conditions, including ocular and cutaneous diseases. NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma and urinary bladder syndromes. Here, we briefly describe the ‘unpredictable’ ideogenesis of the discovery of NGF, a eureka in the neuroscience.
Genistein induces apoptotic cell death associated with inhibition of the NF‐κB pathway in adult T‐cell leukemia cells
Authors: Yamasaki Masao , Mine Yoshihiro , Nishimura Misato , Fujita Satoshi , Sakakibara Yoichi , Suiko Masahito , Morishita Kazuhiro , Nishiyama Kazuo 
Published: August 2013

AbstractWe have shown that genistein inhibits the growth of adult T‐cell leukemia (ATL) cells in vitro and in vivo, and this leads to pronounced G2/M arrest. This report shows that genistein induces apoptotic death in ATL cells. Although the pan‐caspase inhibitor, Z‐VAD‐fmk, did not inhibit genistein‐induced apoptosis, release of apoptosis‐inducing factor (AIF) into the cytosol occurred. Poly‐ADP ribose polymerase inhibition also abrogated genistein‐induced apoptosis. Genistein decreased nuclear p65 translocation and IκBα phosphorylation, and downregulated the anti‐apoptotic proteins, XIAP, cIAP and survivin, NF‐κB‐responsive gene products. Thus, genistein is a promising agent for ATL that induces caspase‐independent apoptosis through inhibition of the NF‐κB pathway.
Effect of bixin and norbixin on the expression of cytochrome P450 in HepG2 cell line
Authors: Matuo Míriam Cristina Sakuragui , de Oliveira Takamoto Rafael Teruiti , Kikuchi Irene Satiko , de Jesus Andreoli Pinto Terezinha 
Published: August 2013

AbstractBixin and norbixin are the main components of annatto, which is extracted from Bixa orellana and largely used as natural colorant in the food and pharmaceutical industries. Annatto can enhance CYP1A and CYP2B activity in rats; however, the inducer effect has not been investigated in human cell lines. In this study, the ability of bixin and norbixin to induce the cytochrome P450 (CYP) enzymes was assessed in HepG2 human hepatoma cell line. HepG2 cells were treated with bixin and norbixin, and the expression of the CYP genes quantified by real‐time reverse transcription polymerase chain reaction (RT‐PCR). Expression of CYP1A1 and CYP1A2 was significantly increased by bixin treatment, while CYP2B6, 2C9, 2E1 and 3A4 were unaffected. Cells were treated with norbixin showed no inducer effect. The results suggest that the inducer potential of annatto is attributed to bixin, but not to norbixin, despite their similarities in molecular structure.
TGF‐β1 induces a nucleus pulposus‐like phenotype in Notch 1 knockdown rabbit bone marrow mesenchymal stem cells
Authors: Morigele Morigele , Shao Zengwu , Zhang Zhicai , Kaige Ma , Zhang Yannan , Qiang Wu , Yang Shuhua 
Published: August 2013

AbstractWe have investigated the effects of Notch1 knockdown and treatment with TGF‐β1 on the regulation of the directional differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from the femur bone of New Zealand rabbits and purified by using discontinuous gradient density centrifugation. Notch1 siRNAs were designed, synthesised and transiently transfected into these MSCs, and treated with TGF‐β1. The MSCs were examined for morphology, stained with toluidine blue for proteoglycan analysis and gene and protein expression were measured with qRT‐PCR and Western blotting respectively. They had an ellipse or fusiform shape and gathered in nests or swirls after being cultured for 7 days. Notch1 expression was knocked down with Notch1 siRNA (the silence rate was 47%; P < 0.001). After knockdown and TGF‐β1 treatment, MSCs expressed more proteoglycan (P < 0.01), and higher levels of collagen II mRNA and protein than control cells (P < 0.001). Thus knockdown of Notch1 expression in MSCs may be useful in the treatment of intervertebral disc degeneration.
Potential of co‐culture of nucleus pulposus mesenchymal stem cells and nucleus pulposus cells in hyperosmotic microenvironment for intervertebral disc regeneration
Authors: Tao Yi‐Qing , Liang Cheng‐Zhen , Li Hao , Zhang Yu‐Jie , Li Fang‐Cai , Chen Gang , Chen Qi‐Xin 
Published: August 2013

AbstractNucleus pulposus mesenchymal stem cells (NPMSCs) are a potential cell source for intervertebral disc (IVD) regeneration, but little is known about their response to IVD‐like high osmolarity (400 mOsm). This study was to investigate the viability, proliferation and protein biosynthesis of nucleus pulposus cells (NPCs), NPMSCs and co‐cultured NPMSCs‐NPCs under IVD‐like high osmolarity conditions. NPCs and NPMSCs were isolated and cultured under standard and IVD‐like high osmolarity conditions for 1 or 2 weeks. Cell viability was measured by annexin V‐FITC and PI staining, and cell proliferation measured by MTT assay. The expression of SOX‐9, aggrecan and collagen‐II was measured by RT‐PCR and Western blot analyses. IVD‐like high osmolarity condition slightly inhibited cell viability and decreased the expression of SOX‐9, aggrecan and collagen‐II at the mRNA and protein levels in all groups compared with standard condition. NPMSCs could tolerate IVD‐like high osmolarity, and NPCs‐NPMSCs co‐culture increased cell proliferation and the expression of SOX‐9, aggrecan and collagen‐II under both culture conditions, suggesting that co‐culture of NPMSCs‐NPCs has potential application for IVD regeneration.
Mechanotransduction in cancer stem cells
Authors: Hao Jin , Zhang Yueling , Ye Rui , Zheng Yingcheng , Zhao Zhihe , Li Juan 
Published: August 2013

AbstractThe cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self‐renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt.
SiRNA‐targeted carboxypeptidase D inhibits hepatocellular carcinoma growth
Authors: Jin Tao , Fu Jie , Feng Xiao‐Jun , Wang Shou‐Mei , Huang Xue , Zhu Ming‐Hua , Zhang Shu‐Hui 
Published: August 2013

AbstractCarboxypeptidase D (CPD), a membrane‐bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non‐tumor liver tissues, as determined by quantitative real‐time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell‐cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell‐cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.