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Zhiqian Zhang, Changli Zhong, Taixian Yuan, Xiaoyan Zhou, Min Zhao, Husun Qian, Wei Cheng, Tingmei Chen
A hybridized chain reaction (HCR)-based biosensing method has been developed for the imaging detection of intracellular telomerase activity. The telomerase-targeting responder-transmitter DNA complex (HPT) consisting of telomerase primer sequence (HP) and a HCR initiator (trigger) is transfected into cell plasma. In the presence of telomerase, HPT can be recognized and extended, producing plenty of triggers which initiates HCR amplification reaction. Finally, a long nicked dsDNA with a lot of outstretched single chains was formed by hybridizing with Q of the reporter complex, generating an enhanced fluorescence signal...
June 20, 2018: Methods and Applications in Fluorescence
Yu-Chen Wang, An-Sheng Lee, Long-Sheng Lu, Liang-Yin Ke, Wei-Yu Chen, Jian-Wen Dong, Jonathan Lu, Zhenping Chen, Chih-Sheng Chu, Hua-Chen Chan, Taha Y Kuzan, Ming-Hsien Tsai, Wen-Li Hsu, Richard A F Dixon, Tatsuya Sawamura, Kuan-Cheng Chang, Chu-Huang Chen
Dysregulation of plasma lipids is associated with age-related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low-density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg-1  day-1 ) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence-associated β-galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5-treated but not L1-treated mice...
June 19, 2018: Aging Cell
Rocio Montejano, Natalia Stella-Ascariz, Susana Monge, José I Bernardino, Ignacio Pérez-Valero, Mª Luisa Montes, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Juan González-Garcia, Javier Rodriguez-Centeno, Berta Rodes, Andres Esteban Cantos, Belen Alejos, Rosa de Miguel, Francisco Arnalich, Rosario Perona, José R Arribas
Background: Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods: Prospective cohort of HIV-1 infected participants with suppressed virological replication, comparing whole blood telomere length (measured by quantitative multiplex PCR) of participants with current exposure versus never exposed to tenofovir disoproxil fumarate. Results: 172 participants included: 67 in the tenofovir disoproxil fumarate (TDF)-group and 105 in the non-TDF group [75 receiving two nucleosides (69 abacavir), 25 receiving a completely nucleos(t)ide sparing regimen, and 5 receiving lamivudine as the only nucleoside]...
June 15, 2018: Journal of Infectious Diseases
Ahmed El-Badawy, Nehal I Ghoneim, Mohamed A Nasr, Hoda Elkhenany, Toka A Ahmed, Sara M Ahmed, Nagwa El-Badri
Telomerase and its core component, telomerase reverse transcriptase (hTERT), are critical for stem cell compartment integrity. Normal adult stem cells have the longest telomeres in a given tissue, a property mediated by high hTERT expression and high telomerase enzymatic activity. In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance. The function of hTERT in CSCs remains poorly understood...
June 15, 2018: Biology Open
Hao Zhang, Ning Hu
Thyroid carcinoma is the most common endocrine malignant tumor in the world, and so, there is a requirement to develop novel molecular targets for thyroid cancer diagnosis and treatment. Telomerase reverse transcriptase (TERT) was revealed to promote cell proliferation in a number of types of cell. To evaluate whether and how TERT functioned on papillary thyroid cancer (PTC) cell proliferation, the present study constructed TERT over‑expression [recombined (r)TERT plasmid group] and interference [small interfering RNA (si)‑TERT group] models by liposome transfection respectively to study the molecular mechanisms...
June 1, 2018: Molecular Medicine Reports
Meng Zhang, Yu Pan, Ranran Jiang, Pingfu Hou, Haixia Shan, Fang Chen, Tao Jiang, Jin Bai, Junnian Zheng
DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry...
June 11, 2018: Oncology Reports
Xin Zhao, Cuicui Zhang, Zhiliang Le, Suyun Zeng, Chaobin Pan, Jianjie Shi, Jianguang Wang, Xiaopeng Zhao
Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is known to induce cell apoptosis in many types of cancer cells. However, some malignant cells still exhibit anti‑apoptosis features induced by TRAIL; thus the underlying mechanisms that regulate sensitivity and resistance of tumor cells to TRAIL‑induced apoptosis remain unclear. Human telomerase reverse transcriptase (hTERT) is overexpressed in most types of human tumors and is mostly inactive in somatic cells. The present study aimed to investigate the endogenous effects and mechanisms of hTERT inhibition and TRAIL overexpression on TRAIL‑induced apoptosis of human oral squamous cell carcinoma (OSCC) cells...
June 7, 2018: International Journal of Molecular Medicine
Jiaoyuan Li, Jiang Chang, Jianbo Tian, Juntao Ke, Ying Zhu, Yang Yang, Yajie Gong, Danyi Zou, Xiating Peng, Nan Yang, Shufang Mei, Xiaoyang Wang, Liming Cheng, Weiguo Hu, Jing Gong, Rong Zhong, Xiaoping Miao
BACKGROUND: Telomere dysfunction triggers cellular senescence and constitutes a driving force for cancer initiation. Genetic variants in genes involved in telomere maintenance may contribute to colorectal cancer (CRC) susceptibility. METHODS: In this study, we firstly captured germline mutations in 192 CRC patients by sequencing the coding regions of 13 core components implicated in telomere biology. Five potential functional variants were then genotyped and assessed in a case-control set with 3,761 CRC cases and 3,839 healthy controls...
June 11, 2018: Cancer Epidemiology, Biomarkers & Prevention
Amy Dressen, Alexander R Abbas, Christopher Cabanski, Janina Reeder, Thirumalai R Ramalingam, Margaret Neighbors, Tushar R Bhangale, Matthew J Brauer, Julie Hunkapiller, Jens Reeder, Kiran Mukhyala, Karen Cuenco, Jennifer Tom, Amy Cowgill, Jan Vogel, William F Forrest, Harold R Collard, Paul J Wolters, Jonathan A Kropski, Lisa H Lancaster, Timothy S Blackwell, Joseph R Arron, Brian L Yaspan
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) risk has a strong genetic component. Studies have implicated variations at several loci, including TERT, surfactant genes, and a single nucleotide polymorphism at chr11p15 (rs35705950) in the intergenic region between TOLLIP and MUC5B. Patients with IPF who have risk alleles at rs35705950 have longer survival from the time of IPF diagnosis than do patients homozygous for the non-risk allele, whereas patients with shorter telomeres have shorter survival times...
June 8, 2018: Lancet Respiratory Medicine
Clement Lin, Guanhui Wu, Kaibo Wang, Buket Onel, Saburo Sakai, Yong Shao, Danzhou Yang
Human telomeres can form DNA G-quadruplex (G4), an attractive target for anticancer drugs. Human telomeric G4s bear inherent structure polymorphism, challenging for understanding specific recognition by ligands or proteins. Protoberberines are medicinal natural-products known to stabilize telomeric G4s and inhibit telomerase. Here we report epiberberine (EPI) specifically recognizes the hybrid-2 telomeric G4 predominant in physiologically relevant K+ solution and converts other telomeric G4 forms to hybrid-2, the first such example...
June 10, 2018: Angewandte Chemie
Lei Chen, Chuan Chen, Wei Chen, Ke Li, Xiaozhen Chen, Xudong Tang, Ganfeng Xie, Xi Luo, Xiaojiao Wang, Houjie Liang, Songtao Yu
Human telomerase reverse transcriptase (hTERT) has been found to be closely related to tumor transformation, growth, and metastasis. Thus, delivery of hTERT small interfering RNA (siRNA) is an important approach for cancer gene therapy. However, single anticancer effect of gene silencing is often limited by poor specificity or low efficiency in siRNA delivery and release. In this work, we present small and thin black phosphorus (BP) nanosheets as a biodegradable delivery system for hTERT siRNA. The BP nanosheets prepared with polyethylene glycol (PEG) and polyethylenimine (PEI) modification (PPBP), exhibited high siRNA loading capacity and robust cell uptake...
June 8, 2018: ACS Applied Materials & Interfaces
Jingjing Jiao, Gordon P Watt, Heather L Stevenson, Tiffany L Calderone, Susan P Fisher-Hoch, Yuanqing Ye, Xifeng Wu, John M Vierling, Laura Beretta
Telomerase reverse transcriptase ( TERT ) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC...
June 2018: Hepatology Communications
Henrik Spåhr, Tiongsun Chia, James P Lingford, Stefan J Siira, Scott B Cohen, Aleksandra Filipovska, Oliver Rackham
DNA is typically found as a double helix, however it must be separated into single strands during all phases of DNA metabolism; including transcription, replication, recombination and repair. Although recent breakthroughs have enabled the design of modular RNA- and double-stranded DNA-binding proteins, there are currently no tools available to manipulate single-stranded DNA (ssDNA). Here we show that artificial pentatricopeptide repeat (PPR) proteins can be programmed for sequence-specific ssDNA binding. Interactions occur using the same code and specificity as for RNA binding...
June 7, 2018: Nature Communications
Hao Tang, Hu Wang, Xiaolei Cheng, Xiuqin Fan, Fan Yang, Mengmeng Zhang, Yanlian Chen, Yuyang Tian, Cihang Liu, Dongxing Shao, Bin Jiang, Yali Dou, Yusheng Cong, Junyue Xing, Xiaotian Zhang, Xia Yi, Zhou Songyang, Wenbin Ma, Yong Zhao, Xian Wang, Jinbiao Ma, Myriam Gorospe, Zhenyu Ju, Wengong Wang
Telomerase consists of the catalytic protein TERT and the RNA TERC. Mutations in TERC are linked to human diseases, but the underlying mechanisms are poorly understood. Here we report that the RNA-binding protein HuR associates with TERC and promotes the assembly of the TERC/TERT complex by facilitating TERC C106 methylation. Dyskeratosis congenita (DC)-related TERC U100A mutation impair the association of HuR with TERC, thereby reducing C106 methylation. Two other TERC mutations linked to aplastic anemia and autosomal dominant DC, G107U, and GC107/108AG, likewise disrupt methylation at C106...
June 7, 2018: Nature Communications
Marta Barrientos-Moreno, Marina Murillo-Pineda, Ana M Muñoz-Cabello, Félix Prado
Upon telomerase inactivation, telomeres gradually shorten with each cell division until cells enter replicative senescence. In Saccharomyces cerevisiae, the kinases Mec1/ATR and Tel1/ATM protect the genome during pre-senescence by preventing telomere-telomere fusions (T-TFs) and the subsequent genetic instability associated with fusion-bridge-breakage cycles. Here we report that T-TFs in mec1Δ tel1Δ cells can be suppressed by reducing the pool of available histones. This protection associates neither with changes in bulk telomere length nor with major changes in the structure of subtelomeric chromatin...
June 2018: PLoS Genetics
Yanhai Jiang, Guozhang Dong, Yeliang Song
BACKGROUND: Mechanical overloading is a risk factor of disc degeneration. Studies have demonstrated that resveratrol helps to maintain the disc cell's healthy biology. OBJECTIVE: This study aims to investigate whether resveratrol can suppress mechanical overloading-induced nucleus pulposus (NP) cell senescence in vitro and the potential mechanism. METHODS: The isolated rat NP cells were seeded in the decalcified bone matrix and cultured under non-compression (control) and compression (20% deformation, 1...
June 6, 2018: Bioscience Reports
Derek B Allison, Rajni Sharma, Morgan L Cowan, Christopher J VandenBussche
OBJECTIVES: Telomerase activity can be detected in up to 90% of urothelial carcinomas (UC). Telomerase activity can also be detected in urinary tract cytology (UTC) specimens and indicate an increased risk of UC. We evaluated the performance of a commercially available antibody that putatively binds the telomerase reverse transcriptase (hTERT) subunit on 500 UTC specimens. STUDY DESIGN: Unstained CytospinTM preparations were created from residual urine specimens and were stained using the anti-hTERT antibody (SCD-A7)...
June 6, 2018: Acta Cytologica
Xuehuo Zeng, Wilnelly Hernandez-Sanchez, Mengyuan Xu, Tawna L Whited, Diane Baus, Junran Zhang, Anthony J Berdis, Derek J Taylor
Telomerase, the end-replication enzyme, is reactivated in malignant cancers to drive cellular immortality. While this distinction makes telomerase an attractive target for anti-cancer therapies, most approaches for inhibiting its activity have been clinically ineffective. As opposed to inhibiting telomerase, we use its activity to selectively promote cytotoxicity in cancer cells. We show that several nucleotide analogs, including 5-fluoro-2'-deoxyuridine (5-FdU) triphosphate, are effectively incorporated by telomerase into a telomere DNA product...
June 5, 2018: Cell Reports
Meng-Ying Liu, Ashley Nemes, Qi-Gang Zhou
Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3' end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs) and neural progenitor cells (NPCs), at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT) can protect newborn neurons from apoptosis and excitotoxicity...
2018: Frontiers in Molecular Neuroscience
Li Zhang, Yenan Wu, Xiang Li, Shao Wei, Yiming Xing, Zhengxing Lian, Hongbing Han
Chicken embryonic stem cells (cESCs) obtained from stage X embryos provide a novel model for the study of avian embryonic development. A new way to maintain cESCs for a long period in vitro still remains unexplored. We found that the cESCs showed stem cell-like properties in vitro for a long term with the support of DF-1 feeder and basic culture medium supplemented with human basic fibroblast growth factor (hbFGF), mouse stem cell factor (mSCF), and human leukemia inhibitory factor (hLIF). During the long culture period, the cESCs showed typical ES cell morphology and expressed primitive stem cell markers with a relatively stable proliferation rate and high telomerase activity...
2018: Stem Cells International
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