Food & Function
·
2021
·Vol. 12
·期 7
·2914-2924
·
IF 5.396
Li Tao,Wei Zhang,Yaxin Zhang,Mei Zhang,Yueying Zhang,Xing Niu,Qing Zhao,Zhenxing Liu,Yuyin Li,Aipo Diao
Telomere shortening is one of the main causes of cellular senescence. Caffeine is a natural stimulant most commonly found in coffee and tea. In this study, caffeine was found to promote the expression of telomerase reverse transcriptase (TERT) at both mRNA and protein levels, and consequently extended the telomere length and prevented cellular senescence. Knockdown of TERT eliminated the effect of caffeine on telomere elongation. Moreover, animal studies indicated that caffeine promoted the expression of TERT and extended the telomere length in the thymus and spleen of mice treated with caffeine for a long period of eight months. In addition, caffeine restored the decline of organ index and improved the histological structural change of the thymus, spleen and liver of mice due to aging. These results suggest that caffeine promotes the expression of TERT to delay cellular senescence and aging, which help to understand the mechanism for the beneficial effects of caffeine containing foods on health.
研究领域:
分子生物学
·
老年学
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营养学
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细胞生物学
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DOI
PubMed
高影响因子
PLoS One
·
2019
·Vol. 14
·期 8
·e0221697
·
IF 2.776
Hung N. Luu,Joyce Y. Huang,Renwei Wang,Jennifer Adams-Haduch,Aizhen Jin,Woon-Puay Koh,Jian-Min Yuan
Introduction
Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study.
Methods
The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors.
Results
Longer telomeres were significantly associated with higher risk of pancreatic cancer ( P trend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25–3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17–8.11) for adenocarcinoma patients and 1.47 (0.43–5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22–5.13) and 1.63 (0.66–4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk.
Conclusions
The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.
研究领域:
肿瘤学
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分子生物学
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流行病学
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遗传学
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转化医学
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DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 11
·1926-1932
·
IF 5.047
Fanyu Meng,Hua Chai,Xiaoyi Ma,Yuguo Tang,Peng Miao
Telomerase catalyzes the elongation of telomeres, which is closely associated with tumorigenesis. Therefore, development of reliable and convenient methods for telomerase activity analysis is critical for clinical diagnosis of cancers. However, most of the current probes for intracellular telomerase activity assay suffer from inevitable false-positive interferences. In this study, we have proposed a novel fluorescence resonance energy transfer (FRET)-based strategy for ultrasensitive monitoring intracellular telomerase activity with an amplification-free procedure. DNA nanoprobes constructed using a DNA tetrahedron and Flare DNA are designed to circumvent the problem of false-positive interference. Generally, telomerase catalyzes DNA extension and changes the configuration of the DNA nanoprobe, which finally leads to the increase of the distance between two labelled fluorophores. Based on the notably decreased FRET efficiency, a simple ratiometric sensor is established for the detection of telomerase activity at the single-cell level, which is much suitable for clinical applications. In addition, this method can be further applied in the detection of telomerase inhibitors, which is important for anti-cancer drug discovery.
研究领域:
分子生物学
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生物技术
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癌症研究
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纳米技术
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生物化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Zhen Zhang,Yuting Jiao,Mengting Zhu,Shusheng Zhang
Here, we propose a strategy for unique nuclear-shell biopolymers initiated by telomere elongation for telomerase activity detection and precise drug delivery to individual cancer cells. Telomerase-triggered DNA rolling-circle amplification (RCA) is used to assemble nuclear-shell biopolymers with signal molecules for selective cancer cell recognition and efficient drug delivery to targeted individual cells. This strategy not only should allow the creation of clustered 5-carboxyfluorescein (FAM)-fluorescence spots in response to human-telomerase activity in individual cancer cells but also could efficiently deliver drugs to reduce the undesired death of healthy cells. These findings offer new opportunities to improve the efficacy of cancer cell imaging and therapy.
研究领域:
癌症生物学
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分子生物学
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生物医学工程
·
药学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 233
·期 12
·9763-9776
·
IF 3.923
Xing Xie,Yuan Gan,Maoda Pang,Guoqing Shao,Lei Zhang,Beibei Liu,Qi Xu,Haiyan Wang,Yanyan Feng,Yanfei Yu,Rong Chen,Meng Wu,Zhenzhen Zhang,Lizhong Hua,Qiyan Xiong,Maojun Liu,Zhixin Feng
Primary porcine bronchial epithelial cells (PBECs) are an ideal model to study the molecular and pathogenic mechanisms of various porcine respiratory pathogens. However, the short lifespan of primary PBECs greatly limit their application. Here, we isolated and cultured primary PBECs and established immortalized PBECs by transfecting primary PBECs with the pEGFP-hTERT recombinant plasmid containing human telomerase reverse transcriptase (hTERT). Immortalized PBECs (hTERT-PBECs) retained the morphological and functional features of primary PBECs as indicated by cytokeratin 18 expression, telomerase activity assay, proliferation assays, karyotype analysis, and quantitative reverse-transcriptase polymerase chain reaction. Compared to primary PBECs, hTERT-PBECs had higher telomerase activity, extended replicative lifespan, and displayed enhanced proliferative activity. Moreover, this cell line is not transformed in vitro and does not exhibit a malignant phenotype in vivo, suggesting that it can be safely used in further studies. Besides, hTERT-PBECs were susceptible to swine influenza virus of H3N2 subtype and porcine circovirus type 2. In conclusion, the immortalized hTERT-PBECs represent a valuable in vitro model, which can be widely used in the study of porcine respiratory pathogenic infections.
研究领域:
细胞生物学
·
病毒学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2013
·
IF 0.769
Yuan-Yuan JIANG,Kun WANG,Chong-Zheng XU,Xiao-Di YANG,Hui-Hui LI
In this work, the glassy carbon electrode modified by alizarin (AR) hybridized with graphene (CRG) and chitosan (CS) was prepared. The AR/CRG-CS electrode exhibited a pair of well-defined reversible redox peaks in 0.1 M phosphate buffer solution (PBS, pH 7.4) with the oxidation peak at −0.573 V and the reduction peak at −0.652 V. It exhibited a two-proton and two-electron redox process and a fast heterogeneous electron transfer rate with the rate constant ( K s ) of 1.69 s −1 using the cyclic voltammetry. Based on the characteristics of alizarin with the decreased current and negative potential shift after binding with human telomere DNA, a sensitive, simple, reliable and stable electrochemical method for the detection of human telomere DNA using the AR/CRG-CS electrode was developed. The electrochemical response showed a linear relationship with DNA concentration in the range of 8.0 × 10 −8 −1.4 × 10 −5 M ( R = 0.9995) with the linear regression equation as Δ I pc (μA) = 8.4860 + 0.5366 C (μmol) and the detection limit ( S/N ) as 2.0 × 10 −8 M.
研究领域:
生物化学
·
材料科学
·
分析化学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Xiaoxia Liu,Xia Li,Jin Li,Bingying Jiang,Ruo Yuan,Yun Xiang
The development of methods that can detect telomerase with high selectivity and sensitivity is critical for early diagnosis and treatment of telomerase-related cancers. In this regard, we describe in this work the establishment of a telomerase-initiated and nicking endonuclease-assisted cascade recycling signal amplification approach for non-label and highly sensitive fluorescent detection of telomerase from cancer cells. The target telomerase triggers the elongation of one strand in a partial dsDNA duplex with a pre-designed sequence to induce the release of a ssDNA, which can initiate three cascaded recycling cycles for the generation of many G-quadruplex sequences by cleaving two hairpin signal probes with the assistance of the Nt.AlwI endonuclease . The thioflavin dye further binds these G-quadruplex sequences to exhibit substantial fluorescence enhancement for sensitive detection of telomerase at 8.93 × 10 −11 IU. Moreover, this developed method is capable of differentiating telomerase activity among different cancer cells and screening telomerase inhibitors for anticancer drugs .
研究领域:
癌症生物学
·
分子诊断学
·
生物技术
·
分析化学
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DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Yingxin Ma,Guobin Mao,Yucheng Zhong,Guoqiang Wu,Wanjun Wu,Yonghao Zhan,Zhike He,Weiren Huang
Telomerase, as a valuable biomarker, is an important target in cancer diagnosis. Here, we report a ratiometric fluorescent probe for telomerase activity assay in urine and bladder cancer diagnoses based on the color change of Rox-DNA functionalized quantum dots (QDs). The green fluorescence of the QDs was sensitive to H 2 O 2 , but the red fluorescence of Rox showed no change. An HRP-mimicking hemin/G-quadruplex, which was formed with the help of telomerase activity, catalyzed H 2 O 2 into H 2 O and O 2 . This quadruplex effectively avoided H 2 O 2 interference with green fluorescence. In the presence of H 2 O 2 , the detected color changed from red to yellow-green by increasing the telomerase concentration. The detection limit (LOD) was 10 cells, and response time was within 60 min. More importantly, a paper sensor was developed based on this probe and used for the assay of telomerase activity in urine samples. The results were highly sensitive and reproducible, and visual semi-quantitative detection was realized using the naked eye.
研究领域:
生物化学
·
医学诊断
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yi Chen,Hengyi Chen,Xiaohui Chen,Yufang Zhang,Wei Tu,Jiaxi Mo,Shanshan Tian,Chenyu Sun,Xiaoqin Meng,Zhizeng Wang,Jichun Yang,Yang Luo
Accurate intracellular visualization of human telomerase RNA (hTR) is imperative for early diagnosis and treatment monitoring of hepatocellular carcinoma (HCC). While isothermal amplification-based DNA cascade strategies are promising, challenges persist in achieving great intake efficiency of detection probes within tumor cells and enhancing intracellular reaction efficiency. This study introduces a SA@Comb-HCR nanosystem , a highly effective approach for in situ hTR detection in HCC cells. Sodium alginate-coated liposomes ensures efficient nanoprobe delivery, which are then combined with proximity effect-inspired signal amplification . The coating of sodium alginate facilitates receptor-mediated endocytosis , prevents serum protein adhesion, and mitigates cationic liposome cytotoxicity. The designed Comb-like consolidated hairpin probe enhances the concentration of the local reactant, resulting in cascade amplification upon hTR activation. This technique achieves precision detection of intracellularly overexpressed hTR in HCC cells with a remarkable detection limit of 0.7 pM. This approach holds great promise for advancing targeted and sensitive early clinical diagnosis of HCC.
研究领域:
分子生物学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xiuping Cao,Liyang Fang,Yifan Jiang,Tao Zeng,Shiyan Bai,Shiqing Li,Yana Liu,Wukun Zhong,Chunhua Lu,Huanghao Yang
Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.
研究领域:
纳米技术
·
肿瘤学
·
分子生物学
·
生物医学工程
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Guixin Han,Ren Kong,Chunsheng Liu,Kai Huang,Qiaolin Xu,Jian Wu,Jiamin Fei,Hui Zhang,Guanyong Su,Robert J. Letcher,Jianbo Shi,Jason R. Rohr
Pesticides have been frequently detected in global freshwater ecosystems, but attempts to document changes in population dynamics of organisms upon exposure to pesticides, establish a causal relationship between exposure and population effects, and identify the key toxic events within individuals under natural field conditions remain rare. Here, we used a field survey, a reciprocal cross-transplant experiment, and a laboratory toxicity experiment to build a compelling case that exposure to the insecticide chlorpyrifos was responsible for differences in snail (Bellamya aeruginosa) densities in eastern (ELL) and western basins of Liangzi Lake in China. Our field survey and reciprocal cross-transplant experiment revealed significant differences in snail densities, juvenile percentage, survival, and relative telomere length (RTL) in the two basins. The insecticide chlorpyrifos detected in snail tissues was negatively correlated with snail densities, the percentage of juvenile snails, and RTL and had an extremely high risk quotient in ELL. In the laboratory experiment, tissue concentrations of chlorpyrifos detected in ELL were associated with reduced RTL and increased juvenile mortality in B. aeruginosa. These results support the hypothesis that chlorpyrifos exposure in ELL reduced the density of snails by reducing juvenile survival and, consequently, recruitment to the adult population.
研究领域:
生态学
·
毒理学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Chao Liu,Hua Zhou,Xiao Bao Sheng,Xin Hua Liu,Fei Hu Chen
Telomerase has become one of the new popular targets for the development of anti-tumor drugs. Based on the structural characteristics of the BIBR1532 which has entered the stage of clinical research, six series total of 64 new compounds with diverse structural characteristics were designed and synthesized. The inhibitory activity against SGC-7901, MGC-803, SMMC-7721, A375 and GES cell lines and their telomerase inhibitory activity were tested. Among them, eight compounds showed good activity against cancer cells, among them compounds 56 , 57 and 59 also showed low toxicity. Some of them showed excellent telomerase inhibitory activity with IC 50 values ranging from 0.62 μM to 8.87 μM. Based on above, in depth structure-activity relationships were summarized, the compounds by replacing methyl group with cyanide and retaining amide moiety had good anti-tumor activity, moderate cytotoxicity, and better telomerase inhibitory activity. The results should be used for reference in BIBR1532-based structural optimization for further development of small molecule telomerase inhibitors.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）