bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA TUG1 promotes cell proliferation and migration of renal cell carcinoma via regulation of YAP
Authors: Liu Shan , Yang Yantong , Wang Weiwei , Pan Xiaoyue 
Published: August 2018

AbstractObjectives: Recently, long noncoding RNAs (lncRNAs) have captured much attention for their important roles in human diseases. Deregulation of lncRNA taurine‐upregulated gene 1 (TUG1) has been reported to regulate cancer progression in many cancer types. However, how TUG1 contributes to renal cell carcinoma (RCC) remains elusive; we were eager to resolve the questions.Methods: Tumor tissues and the matched adjacent normal tissues were collected from patients with RCC. Messenger RNA (mRNA) levels of TUG1, yes‐associated protein (YAP), and microRNA (miR)‐9 levels were determined by reverse transcription quantitative polymerase chain reaction (RT‐qPCR). The regulation of YAP by TUG1 was investigated using Western blot analysis, RT‐qPCR, and immunofluorescence. The oncogenic roles of TUG1 and YAP were studied using a cell proliferation assay and a wound healing assay. The interaction of TUG1‐miR‐9‐YAP was analyzed in RCC cell lines.Results: In the current study, we observed a positive correlation between TUG1 expression and YAP expression in RCC using the Gene Expression Omnibus database and tumor tissues collected from 58 patients with RCC. The TUG1 elevation enhanced YAP expression but did not alter the Hippo‐signaling pathway activity or YAP protein distribution in cells. In addition, we found that TUG1 could bind to miR‐9; therefore, TUG1 could positively control YAP expression via downregulation of miR‐9 level. Furthermore, we observed that inhibition of cell proliferation and cell migration induced by TUG1 silencing could be reversed by overexpression of YAP in RCC cell lines.Conclusions: Our findings indicated a pivotal role of TUG1 in driving RCC progression via regulation of miR‐9/YAP, suggesting a potential therapeutic targeting role of TUG1 in RCC.
Docosahexaenoic acid attenuates the detrimental effect of palmitic acid on human endothelial cells by modulating genes from the atherosclerosis signaling pathway
Authors: Novinbahador Tannaz , Nourazarian Alireza , Asgharzadeh Mohammad , Rahbarghazi Reza , Avci Çıgır Biray , Bagca Bakiye Goker , Ozates Neslihan Pinar , Karbasforoush Saeede , Khaki‐Khatibi Fatemeh 
Published: August 2018

AbstractThe formation of atherosclerotic changes leads to dysfunction in numerous cell types, especially endothelial cells. In the current experiment, we aimed to show the therapeutic effect of Docosahexaenoic acid on palmitic‐induced atherosclerotic changes in the human endothelial lineage. Human Umbilical Vein Endothelial cells were incubated with 1 mM palmitic acid for 48 hours and then exposed to 40 µM docosahexaenoic acid for next 24 hours. Cellular atherosclerosis and lipid removal were confirmed by the application of Oil red O solution. The cell survival rate was studied by using MTT assay and flow cytometry analysis of Annexin V. We also measured the protein level of tumor necrosis factor‐α and granulocyte‐macrophage colony‐stimulating factor by immunofluorescence imaging. The transcription level of genes participating in the atherosclerosis signaling pathway was monitored in atherosclerotic endothelial cells before and after treatment with docosahexaenoic acid. The viability of the cells was reduced after 48 hours incubation with palmitic acid. It is noteworthy that the number of viable endothelial cells was increased after exposure to docosahexaenoic acid. Compared with the cells that received palmitic acid, Oil red O staining showed a decrease in the cellular content of fatty acid after incubation with docosahexaenoic acid (P < 0.05). PCR array indicated that the modulation of key genes played a role in atherosclerosis and reached near‐control levels. These data support the notion that incubation of atherosclerotic human endothelial cells with docosahexaenoic acid could return the detrimental effects of palmitic acid by modulation of the atherosclerosis signaling pathway.
MMP‐9 gene rs3918242 polymorphism increases risk of stroke: A meta‐analysis
Authors: Wang Baohua , Wang Yinhua , Zhao Lei 
Published: August 2018

AbstractThe association between matrix metalloproteinase‐9 (MMP‐9) gene rs3918242 polymorphism and the risk of stroke has been investigated, but the findings have been found to be contradictory. Thus, this association was assessed by meta‐analysis. Potential studies were searched throughout PubMed, Embase, and CNKI. Pooled odds ratios and 95% confidence intervals were calculated. Sixteen original studies analyzing this association were included, involving 3647 stroke patients and 3685 unrelated controls. It was confirmed that MMP‐9 gene rs3918242 polymorphism increased the risk of stroke. Stratification analysis of ethnicity revealed an increased risk of stroke among Asians, but not among Caucasians. Subgroup analysis by the type of stroke showed that MMP‐9 gene rs3918242 polymorphism increased the risk of ischemic stroke. Sensitivity analysis did not draw different findings. In conclusion, MMP‐9 gene rs3918242 polymorphism increases the risk of stroke.
Intracellular protons accelerate aging and switch on aging hallmarks in mice
Authors: Osanai Tomohiro , Tanaka Makoto , Izumiyama Kei , Mikami Kasumi , Kitajima Maiko , Tomisawa Toshiko , Magota Koji , Tomita Hirofumi , Okumura Ken 
Published: August 2018

AbstractDiet‐induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. The serum bicarbonate level is an independent predictor of chronic kidney disease progression. We investigated whether proton accelerates aging by analyzing both coupling factor 6‐overexpressing transgenic (TG) and high salt‐fed mice which display sustained intracellular acidosis, due to enhanced proton import through ecto‐F1Fo complex and/or reduced proton export through Na+‐K+ ATPase inhibition. Both types of mice displayed shortened lifespan and early senescence‐associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In chronic intracellular acidosis mice, autophagy was impaired by regression of Atg7, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. The increase in histone 3 trimethylation at lysine 4 (H3K4me3) and H4K20me3 and the decrease in H3K9me3 and H3K27me3 were observed in the heart and kidney obtained from both TG and high salt‐fed mice. The decrease in lamin A/C, emerin, and heterochromatin protein 1α without changes in barrier‐to‐autointegration factor and high‐mobility group box 1 was confirmed in TG and high salt‐fed mice. Suppression of nuclear histone deacetylase 3‐emerin system is attributable to epigenetic regression of Atg7 and H4K5 acetylation. These findings will shed light on novel aging and impaired autophagy mechanism, and provide implications in a target for antiaging therapy.
Gene therapy in cardiovascular diseases: A review of recent updates
Authors: Gorabi Armita M. , Hajighasemi Saeideh , Tafti Hossein A. , Soleimani Masoud , Panahi Yunes , Ganjali Shiva , Sahebkar Amirhossein 
Published: August 2018

AbstractGene therapy is considered as a promising approach for treating cardiac dysfunction. In this review, we evaluated the clinical trials assessing gene therapy in cardiovascular diseases (CVD) from 2000 to 2017. PubMed and ClinicalTrials.gov (only English language) were searched for clinical trials published between January 2000 and May 2017, using the search terms “gene transfer” OR “gene therapy” and “cardiovascular diseases” and related terms. The trials with sample size lower than 10 patients were excluded. Twenty‐six clinical trials on human and animals, including 1543 patients were listed and evaluated. The sample size in 14 trials was lower than 100 patients and in seven trials lower than 20 patients. Eleven trials used plasmid DNA and eight trials used adenovirus, one study used plasmid DNA, adenovirus, and liposome. We detected that gene therapy was a safe approach and improved the symptoms of CVD; however, the effect of gene therapy on the cardiac dysfunction is controversial.
Establishment and characterization of human theca stem cells and their differentiation into theca progenitor cells
Authors: Dalman Azam , Totonchi Mehdi , Valojerdi Mojtaba Rezazadeh 
Published: August 2018

AbstractIn this study, we have characterized the human theca stem cells (hTSCs) and their differentiation into human theca progenitor cells (hTPCs). hTSCs were isolated from the theca layer of small antral follicles (3‐5 mm in size). Alkaline phosphatase activity, cell cycle status, and cell surface markers were evaluated in hTSCs. The differentiation potential of these cells was investigated via differentiation of hTSCs into adipocyte‐, osteocyte‐, and chondrocyte‐like cells. The cells also differentiated into hTPCs. The hTSCs were morphologically similar to human fibroblast cells (hFCs). Some of the cells were positive for alkaline phosphatase activity. The expression of OCT4 in hTSCs was significantly higher than that of human bone marrow mesenchymal stem cells (hBMSCs) and hFCs. To determine the type of OCT4 (isoform A or B), RT PCR was performed. The data showed that OCT‐4A was expressed in hBMSCs and hTSCs but immunofluorescence analyses using the OCT‐4A‐specific and OCT4 antibodies did not show OCT‐4A protein. In addition, cell cycle status showed that the number of hTSCs in the S phase was significantly higher than that of hFCs. CD29, CD44, CD73, CD90, and CD105 were present in hTSCs. Osteogenic, adipogenic, and chondrogenic differentiation was confirmed by cytochemical staining and lineage‐specific transcripts. Our results showed that specific Dulbecco modified Eagle medium F12 culture medium results in the presence of hTPC markers. hTPCs displayed lipid droplets, appropriate gene expression, and secreted dehydroepiandrosterone and estradiol. hTSCs have the ability to differentiate into mesenchymal lineages and hTPCs. This study may provide a novel in vitro model for further investigation of theca cell maturation and differentiation.
Inhibition of lncRNA X inactivate‐specific transcript ameliorates inflammatory pain by suppressing satellite glial cell activation and inflammation by acting as a sponge of miR‐146a to inhibit Nav1.7
Authors: Sun Wenbo , Ma Meina , Yu Hongmei , Yu Hong 
Published: August 2018

AbstractLong noncoding RNAs (lncRNA) has been validated to participate in nociception in inflammatory pain, presenting as a potential target against anesthesia. Previous research work confirmed the correlation between lncRNA X inactivate–specific transcript (XIST) and inflammation. However, its role in inflammatory pain is undefined. In animal pain models, voltage‐gated sodium channels (VGSCs) reportedly participate in neural excitation. In this study, we observed the high expression of XIST and VGSC 1.7 (Nav1.7) in the dorsal root ganglion (DRG) of the complete Freund’s adjuvant (CFA)‐induced rat inflammatory pain model. Furthermore, XIST inhibition alleviated pain behavior and the activation of DRG satellite glial cells by suppressing glial fibrillary acidic protein (GFAP) expression, as well as inflammatory cytokine levels of interleukin‐6 and tumor necrosis factor‐α. XIST downregulation increased the mechanical pain threshold in an inflammatory pain model. Moreover, the expression of miR‐146a was decreased in CFA rats. In vitro, XIST acted as a sponge of miR‐146a, which targeted Nav1.7 via bioinformatic prediction, luciferase reporter, and pull‐down assay. More importantly, activation of the Nav1.7 pathway or miR‐146 depression both reversed XIST knockdown–inhibited satellite glial cell activation and inflammatory pain in CFA rats. These results suggest that cessation of XIST may ameliorate inflammatory pain by acting as a sponge of miR‐146a to inhibit Nav1.7, implying a promising strategy against inflammatory pain.
Retracted: Inositol polyphosphate‐4‐phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3‐kinase/protein kinase B pathway
Authors: Li Dong , Yang Jingyan , Ma Huanzhi , Sun Chengliang , Feng Rongjie 
Published: August 2018

AbstractOsteosarcoma (OS) is an aggressive malignant tumor of bone, which often occurs in children and adolescents. Currently, the effective method for the treatment of OS is still limited. The study aimed to investigate the synergistic antitumor effect of inositol polyphosphate‐4‐phosphatase, type‐II (INPP4B) and rucaparib on OS cells. The expression levels of INPP4B in OS tissues and OS cell lines were examined by quantitative real‐time polymerase chain reaction and Western blot analysis. SaOS2 and U2OS cells were then transfected with overexpression vector of INPP4B or were treated with different concentrations of rucaparib, and cell viability, cell cycle, and apoptosis were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and flow cytometry. Western blot assay uncovered the combined effects of INPP4B and rucaparib on cell cycle, apoptosis and phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) signal pathway. Further, the tumor formation was examined in vivo. Results showed that INPP4B was low expressed in OS tissues and in OS cell lines. INPP4B overexpression significantly decreased cell viability and induced apoptosis in SaOS2 and U2OS cells. Additionally, rucaparib remarkably reduced cell viability in a dose‐dependent and time‐dependent manner. Meanwhile, rucaparib suppressed cell cycle progression in the S phase and promoted apoptosis in a dose‐dependent manner. Further, combination of INPP4B overexpression and rucaparib declined Myc, cyclin E1 and cyclin D1 expressions, enhanced Bad, Bax, and cleaved‐caspase‐3 expressions, and blocked PI3K/AKT signal pathway in SaOS2 and U2OS cells. Finally, combination of INPP4B overexpression and rucaparib inhibited tumor formation in vivo. The study demonstrated that INPP4B and rucaparib exhibited synergistic antitumor effect by regulating PI3K/AKT pathway in OS cells.
Hsa‐miR‐5582‐3P regulatory effect on TGFβ signaling through targeting of TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 transcripts
Authors: Abedini Bakhshmand Elham , Mohammad Soltani Bahram , Fasihi Ali , Mowla Seyed Javad 
Published: August 2018

AbstractTransforming growth factor β (TGFβ) signaling pathway which is regulated by factors such as microRNAs (miRNAs) has pivotal roles in various cellular processes. Here, we intended to verify bioinformatics predicted regulatory effect of hsa‐miR‐5582‐3P against TGFβ/SMAD signaling pathway components. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) analysis indicated a negative correlation of expression between hsa‐miR‐5582‐3P against TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 putative target genes in all of tested cell lines. Also, hsa‐miR‐5582‐3P was significantly downregulated in glioma, breast, and ovarian tumor tissues compared with their normal pairs, detected by RT‐qPCR. Then dual luciferase assay supported direct interaction between this miRNA and TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4, 3′ untranslated region sequences. Western blot analysis confirmed negative effect of hsa‐miR‐5582‐3P overexpression on at least TGFβ‐R1 expression. Consistently, hsa‐miR‐5582‐3P overexpression brought about downregulation of TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 expression in HCT‐116 cell line, followed by cell cycle arrest in sub‐G1 phase, detected by flow cytometry. Altogether, our data suggest that hsa‐miR‐5582‐3P reduces the TGFβ/SMAD signaling pathway through downregulation of TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 transcripts. These data introduce hsa‐miR‐5582‐3P as a potential tumor suppressors‐miR and a therapy candidate to be tested in cancers in which TGFβ/SMAD is deregulated.
Z‐band and M‐band titin splicing and regulation by RNA binding motif 20 in striated muscles
Authors: Chen Zhilong , Maimaiti Rexiati , Zhu Chaoqun , Cai Hanfang , Stern Allysa , Mozdziak Paul , Ge Ying , Ford Stephen P. , Nathanielsz Peter W. , Guo Wei 
Published: August 2018

AbstractTitin (TTN) has multifunctional roles in sarcomere assembly, mechanosignaling transduction, and muscle stiffness. TTN splicing generates variable protein sizes with different functions. Therefore, understanding TTN splicing is important to develop a novel treatment for TTN‐based diseases. The I‐band TTN splicing regulated by RNA binding motif 20 (RBM20) has been extensively studied. However, the Z‐ and M‐band splicing and regulation remain poorly understood. Herein, we aimed to define the Z‐ and M‐band splicing in striated muscles and determined whether RBM20 regulates the Z‐ and M‐band splicing. We discovered four new Z‐band TTN splicing variants, and one of them dominates in mouse, rat, sheep, and human hearts. But only one form can be detected in frog and chicken hearts. In skeletal muscles, three new Z repeats (Zr) were detected, and Zr4 to 6 exclusion dominates in the fast muscles, whereas Zr4 skipping dominates in the slow muscle. No developmental changes were detected in the Z‐band. In the M‐band, two new variants were discovered with alternative 3′ splice site in exon363 (Mex5) and alternative 5′ splice site in intron 362. However, only the sheep heart expresses two new variants rather than other species. Skeletal muscles express three M‐band variants with altered ratios of Mex5 inclusion to Mex5 exclusion. Finally, we revealed that RBM20 does not regulate the Z‐ and M‐band splicing in the heart, but does in skeletal muscles. Taken together, we characterized the Z‐ and M‐band splicing and provided the first evidence of the role of RBM20 in the Z‐ and M‐band TTN splicing.
Apoptotic effect of resveratrol on human T‐ALL cell line CCRF‐CEM is unlikely exerted through alteration of BAX and BCL2 promoter methylation
Authors: Zadi Heydarabad Milad , Vatanmakanian Mousa , Abdolalizadeh Jalal , Mohammadi Hamed , Azimi Ako , Mousavi Ardehaie Reza , Movasaghpour Aliakbar , Farshdousti Hagh Majid 
Published: August 2018

AbstractOne of the fundamental barriers leading to failure of leukemia therapy is the resistance against conventional chemotherapies, common modality used to cure leukemia. Having the potential to trigger apoptosis in various human leukemia cell lines, resveratrol is regarded as a robust agent in chemotherapy regimens. The current study was aimed to assess whether the apoptotic effect of resveratrol on T‐cell acute lymphoblastic leukemia cell line, CCRF‐CEM, is exerted through DNA methylation of BAX and BCL2 gene promoters. For this purpose, the CCRF‐CEM cells were treated by resveratrol under standard cell culture. To analyze the promoter DNA methylation changes, we used methylation‐specific polymerase chain reaction technique following the resveratrol treatment at different dosages and time intervals. Based on our previous study, the resveratrol treatment can trigger apoptosis in CCRF‐CEM cell line via upregulation of apoptotic BAX gene and downregulation of antiapoptotic BCL2 gene. Despite these alterations in gene expression, the current study reveals no changes in DNA methylation patterns of subjected genes following the resveratrol treatment. Unchanged status of DNA methylation of BAX and BCL2 genes may suggest that resveratrol causes the gene expression changes through a distinct mechanism which requires further studies to be understood.
Retracted: Knockdown of long noncoding RNA urothelial carcinoma–associated 1 inhibits cell viability, migration, and invasion by regulating microRNA‐182 in gastric carcinoma
Authors: Qin Lei , Jia Zhihua , Xie Dawei , Liu Zhongyuan 
Published: August 2018

AbstractBackgroundLong noncoding RNA urothelial carcinoma–associated 1 (UCA1) has been reported to be a vital mediator in various cancers. But, in terms of gastric cancer (GC), the effects of UCA1 on GC cell proliferation, migration, invasion, and apoptosis remain unclear. This study aimed to uncover the potential regulatory mechanism of UCA1 in GC cells.MethodsThe expression level of UCA1 was first examined in the five different cell lines of HEK293, CCL‐153, HUVEC, SUN‐216, and SGC‐7901 using a reverse‐transcriptase quantitative polymerase chain reaction. Then, the vectors of short hairpin UCA1, the microRNA‐182 (miR‐182) mimic/inhibitor, and the pEX‐tissue inhibitor of metalloproteinases 2 (TIMP2)/small interfering TIMP2 were transfected into SUN‐216 and SGC‐7901 cells to alter UCA1, miR‐182, and TIMP2 expression. To investigate the biological functions, cell viability, migration, invasion, and apoptosis were examined by Cell Counting Kit‐8, Transwell, and flow cytometry. The key factors of apoptosis and phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) and nuclear factor κB (NF‐κB) signal pathways were determined by Western blot analysis.ResultsUCA1 was upregulated in SUN‐216 and SGC‐7901 cells than in the other three cell lines of HEK293, CCL‐153, and HUVEC. Knockdown of UCA1 significantly suppressed cell viability, migration, and invasion, and promoted apoptosis by regulating B‐cell lymphoma 2, Bax, and cleaved‐caspase‐3/9 expressions. However, miR‐182 overexpression markedly reversed the regulatory effect of UCA1 knockdown on SUN‐216 and SGC‐7901 cells. TIMP2 was a direct target gene of miR‐182, and TIMP2 overexpression exhibited the same effect of UCA1 knockdown on cell viability, migration, invasion, and apoptosis. Besides, miR‐182 activated PI3K/AKT/GSK3β and NF‐κB signal pathways by regulation of TIMP2.ConclusionKnockdown of UCA1 exerts an anticancer effect on GC cells by regulating miR‐182.
Effect of resveratrol on Sertoli cell proliferation
Authors: Gorga A , Rindone GM , Regueira M , Pellizzari EH , Camberos MC , Cigorraga SB , Riera MF , Galardo MN , Meroni SB 
Published: August 2018

AbstractResveratrol (RSV), a polyphenolic compound largely found in red grape skin, has been used as a nutritional supplement as it exhibits beneficial health effects, such as anticancer, cardioprotective, antiaging, and anti‐inflammatory. Particularly, it has been shown that it participates in the mechanisms involved in cell proliferation. Sirtuin 1 (SIRT1) is considered a well‐known RSV effector. Noteworthy, Sirt1‐knockout animals are infertile. The aim of this study was, first, to determine whether RSV has any effect on Sertoli cell proliferation and, second, whether SIRT1, a putative target of RSV, is present in immature Sertoli cells. Sertoli cell cultures obtained from 8‐day‐old rats, which actively proliferate, were treated with RSV (10 and 50 µM) under basal and follicle‐stimulating hormone (FSH)‐stimulated conditions. Bromodeoxyuridine (BrdU) incorporation and the expression of cyclins D1, D2, D3, E1, and E2 and the Cip/Kip cell cycle inhibitors p21Cip and p27Kip were analyzed. RSV decreased BrdU incorporation and cyclins D1, D2, E1, and E2 expression and increased p21Cip and p27Kip messenger RNA (mRNA) levels. RSV also decreased FSH‐stimulated BrdU incorporation and cyclins D1 and D2 mRNA levels. The effect of RSV on cMYC was also analyzed. RSV treatment did not modify basal and FSH‐stimulated cMyc expression; however, it inhibited basal and FSH‐stimulated cMYC transcriptional activity, suggesting a role of cMYC in RSV effects. Additionally, Sirt1 was detected in immature Sertoli cells. Altogether, these results suggest that RSV possibly, by activating SIRT1 and regulating cMYC transcriptional activity, participates in the regulation of immature Sertoli cell proliferation.