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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng Nan Hu Zhi-Hao Wang Chang-Cheng Tao Ya-Ru Wang Yue Liu Zulihumaer Aizimuaji Hong-Wei Wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Hernia Surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,

关键词： telomerase Bibliometric analysis telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

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Construction of MTX-CS-TMP-NPs Nano-drug Delivery System and its Observation on telomerase Activity of Cervical Cancer Hela Cells

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Chinese Journal of Biomedical Engineering(English Edition) 2024年第1期33卷 27-32,39页

作者： YAN Xiao-shuai LUO Chao YANG Fang The Fifth Hospital of Xianmen Xiamen Fujian 361101China

Objective:To construct methotrexate(MTX)-chitosan(CS)-chuanxiongmuizine(TMP)nano-delivery system MTX-CS-TMP-NPs,and to investigate its effect on the telomerase activity of cervical cancer Hela cells.Methods:MTX-CS and MTX-CS-TMP-NPs were prepared by amide reaction and ionic gel method,and the encapsulation rate and drug loading rate were observed.MTT method and TRAP method were used to detect Hela cells and telomerase activity,and to compare the difference of telomerase activity of MTX,MTX-CS,and MTX-CS-TMP-NPs on cervical cancer Hela cells.Results:In this study,the total amount of TMP was 150μg,of which the amount of free TMP was(26.46±1.72)μg,the encapsulation rate of TMP was(82.36±0.01)%,and the drug loading was(17.62±0.23)mg.The activity of Hela cells increased with the extension of time,and the OD value of Hela cell activity(1.24±0.05)was lower than that of the other three groups at 72 h of treatment,and the difference was statistically significant(Ptelomerase activity of He La cells in the MTX-CS-TMP-NPs solution treatment group was(0.23±0.12)%lower than that of the other three groups,with statistically significant difference(Ptelomerase activity of cervical cancer Hela cells,showing its potential anti-cervical cancer effect.

关键词： cervical cancer(CC) Docetaxel MTX telomerase nano-drug delivery system cell cycle

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telomerase and neurons:an unusual relationship

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Neural Regeneration Research 2022年第11期17卷 2364-2367页

作者： Gabriele Saretzki Biomedical Sciences Campus for Ageing and VitalityNewcastle UniversityNewcastle Upon TyneUK

Most people associate the enzyme telomerase with its role in maintaining telomeres,which is its best-known canonical role.For this important function,two main components are required:the protein telomerase reve rse transcriptase(TERT)and the telomerase RNA component.In addition,over the last decades,an ever-growing number of othe r,non-telomeric,non-canonical functions for the telomerase protein TERT has been established.These reach from tumor promotion to decreasing oxidative stress and apoptosis as well as activating autophagy.These functions are more and more recognized as being important in many tissues and physiological as well as pathological conditions.The role of telomerase in brain development and neuronal cells has been investigated for more than 20 years.However,the non-telomeric role in non-dividing neurons of the brain for telomerase and the TERT-protein has only recently been highlighted by extensive research.Moreover,these developments promoted the suggestion of a beneficial and protective role of TERT against neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.This review summarizes the most important findings in the field of telomerase in neuro ns and gives an outlook onto possible therapeutic applications of boosting telomerase/TERT levels with telomerase activators to prevent or ameliorate various neurodegene rative diseases.

关键词： autophagy brain neurons neurodegeneration telomerase TERT protein

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Visually Intracellular Detection of telomerase Activity Based on DNA Strand Displacement Reaction and Gold Nanoparticle Labeling

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Chinese Journal of Chemistry 2022年第6期40卷 693-698页

作者： Yajun Zhang Shen Yan Zhaoxin Chen Xin Jiang Shuang Rao Zhuoran Jiang Shanshan Qin Xiang Zhou Yuhao Du College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers of Ministry of EducationWuhan UniversityWuhanHubei 430072China

telomerase,which is regarded as a common biomarker for early cancer diagnostics and a potential target for clinical therapies,has attracted considerable interests concerning its detection and monitoring.Herein,we propose a sensitive method by designing a gold nanoparticle(AuNP)probe for visually intracellular detection of telomerase activity.The AuNPs were functionalized with a telomer-ase substrate primer(SH-prime).A 6-carboxy-fluorescein(FAM)modified strand(FAM-probe)was attached to the surface of AuNP through its complementary stand(SH-attach).In the absence of telomerase,the fluorescence resonance energy transfer(FRET)from FAM to AuNPs results in efficient fluorescence quenching.In the presence of telomerase,SH-primers on AuNPs were extended with the repeat units(TTAGGGG)n.The extension sequence triggered the strand displacement of FAM-probe to restore the fluorescence signals.It is worth mentioning that the proposed strategy does not need to design complex hairpin structure and allows the meas-urement of telomerase in crude cell extracts down to 0.5 HeLa cells/μL in 2 h.In addition,the present sensing platform can be ap-plied to the visually intracellular detection of telomerase activity in living cells.

关键词： telomerase Nanoparticles DNA strand displacement Intracellular FRET

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telomerase Activity and telomerase Reverse Transcriptase Expression Induced by Selenium in Rat Hepatocytes

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Biomedical and Environmental Sciences 2009年第4期22卷 311-317页

作者： RI-AN YU HUA-JIE CHEN LING-FEI HE BING CHEN XUE-MIN CHEN Department of Occupational and Environmental Health School of Public Health Guangdong Pharmaceutical University Guangzhou 510310 Guangdong China Department of Occupational and Environmental Health MOE Key Laboratory of Environment and Health School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei China Department of Dental Medicine The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080 Guangdong China

Objective To investigate the effects of sodium selenite on telomerase activity, apoptosis and expression of TERT, c-myc and p53 in rat hepatocytes. Methods Selenium at doses of 2.5, 5.0, and 10 μmol/kg was given to SD rats by garage. In rat hepatocytes, telomerase activity was measured by the telomeric repeat amplification protocol （TRAP）, apoptosis was detected by flow cytometry, and expressions of telomerase reverse transcriptase （TERT）, c-myc and p53 were analyzed by reverse transcription-polymerase chain reaction （RT-PCR）. c-Myc and P53 proteins were detected by immunochemistry. Results Selenium at doses of 2.5, 5.0, and 10 μmol/kg significantly increased hepatocellular telomerase activity and induced apoptosis in a dose-dependent manner. Although selenium at doses of 2.5, 5.0, and 10 μmol/kg displayed no obvious enhancing effect on the TERT mRNA expression in rat hepatocytes （P〉0.05）, it significantly increased the c-myc mRNA and p53 mRNA expression at the dose of 10 μmol/kg （P〈0.05）. Selenium at doses of 5.0 and 10 μmol/kg obviously increased the content of P53 protein in rat hepatocytes, but only at the dose of 10 μmol/kg, it significantly promoted the value of c-Myc protein in them. Conclusion Selenium can slightly increase telomerase activity and TERT expression, and significantly induce apoptosis and over-expression of c-myc and p53 at relatively high doses. The beneficial effects of selenium on senescence and aging may be mediated by telomerase activation and expression of TERT, c-myc, and p53 in rat hepatocytes.

关键词： Selenium telomerase telomerase reverse transcriptase c-myc p53

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telomerase reactivation is associated with hepatobiliary and pancreatic cancers

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Hepatobiliary & Pancreatic Diseases International 2020年第5期19卷 420-428页

作者： Vito Sansone Marco Le Grazie Jenny Roselli Simone Polvani Andrea Galli Francesco Tovoli Mirko Tarocchi Department of Medical and Surgical Sciences University of BolognaBolognaItaly Department of Experimental and Clinical Biomedical Sciences"Mario Serio" University of Florence50139 FirenzeItaly

Background:Human telomerase reverse transcriptase(hTERT)and its components play a significant role in cancer progression,but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases;increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic diseases.Data sources:We performed a PubMed search with the following keywords:telomerase,hepatocellular carcinoma,cholangiocarcinoma,pancreatic adenocarcinoma by December 2019.We reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic diseases.Results:telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers,as a predictor for prognosis and a promising therapeutic target.Conclusions:Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases.

关键词： telomerase Telomere Cancer Hepatobiliary and pancreatic disease

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telomerase activity in cervical intraepithelial neoplasia

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Chinese Medical Journal 2004年第2期17卷 202-206页

作者：王淑珍孙建衡张伟金顺钱王洪平金玉生曲萍刘毅李茉 Department of Obstetrics and Gynecology Chaoyang HospitalCapital University of Medical Sciences Beijing 100020 China Department of Gynecological Oncology Cancer Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100021 China Department of Centre for Tumor Assay Cancer Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100021 China

Background It was reported that telomerase expression is closely associated with cellular immortality and cancer. This study was designed to investigate the relationship between telomerase expression and the carcinogenesis of cervical cancer, the possible use of telomerase as a marker of cervical intraepithelial neoplasia (CIN) progression or regression, and the natural history of CIN.Methods Telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in cervical scrapings and biopsy samples obtained from 105 cases affected with various cervical conditions, including chronic cervicitis (n =20), CIN (n =64, 16 cases of CIN Ⅰ , 20 cases of CIN Ⅱ , and 28 cases of CIN Ⅲ), and invasive squamous cell carcinoma (n =21).Results In exfoliated cell samples, telomerase activity was detected in 5 of 20 (25. 0%) cases of cervicitis, 10 of 16 (62. 5%) cases of CIN Ⅰ , 11 of 20 (55. 0%) cases of CIN Ⅱ , 23 of 28 (82.1%) cases of CIN Ⅲ, and 13 of 21 (61. 9%) cases of carcinoma. In cervical biopsy samples, telomerase activity was detected in 6 of 20 (30. 0%) cases of cervicitis, 8 of 16 (50. 0%) cases of CIN Ⅰ , 9 of 20 (45. 0%) cases of CIN Ⅱ , 27 of 28 (96. 4%) cases of CIN Ⅲ, and 20 of 21 (95. 2%) cases of carcinoma. telomerase activation was significantly higher in CIN samples than in cervicitis samples. telomerase activity was detected at similar frequency in samples from cervical scrapings and cervical biopsies.Conclusion These results seem to suggest that telomerase expression may be associated with carcinogenesis of the cervix. TRAP assay of cervical scraping samples could be used to monitor and predict the development of CIN in clinical practice.

关键词： cervical intmepithelial neoplasia telomerase enzymology cervix neoplasm

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telomerase and mTOR in the brain:the mitochondria connection

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Neural Regeneration Research 2017年第3期12卷 358-361页

作者： Satomi Miwa Gabriele Saretzki Ageing Biology Centre and Institute for Cell and Molecular Biosciences Campus for Ageing and VitalityNewcastle UniversityNewcastle upon TyneUK

telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component.Additionally,the protein part TERT（telomerase Reverse Transcriptase） has various non-canonical functions.For example,it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress,DNA damage and apoptosis.Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well.We have recently published that TERT protein accumulated in mitochondria from brain tissue of mice that have undergone short-term dietary restriction（DR） and rapamycin treatment.This localization correlated to lower levels of oxidative stress in these brain mitochondria.Since rapamycin treatment decreases mTOR signaling which is also thought to play an important role for the beneficial effects of DR,we conclude that the mTOR pathway might be involved in the TERT localization and its effects in brain mitochondria in vivo.These data are in line with previous findings from our group about increased mitochondrial localization of TERT in Alzheimer＇s disease（AD） brains and a protective function of TERT protein in neurons in vitro against pathological tau.

关键词： telomerase brain neuron mitochondria roTOR ROS dietary restriction rapamycin

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telomerase expression in the glial scar of rats with spinal cord injury

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Neural Regeneration Research 2012年第11期7卷 810-814页

作者： Mingkun Yang Weibin Sheng Tao Xu Kai Huang Yanjiao Wang Department of Spinal Surgery First Affiliated Hospital Xinjiang Medical University Urumqi 830054 Xinjiang Uygur Autonomous Region China Department of Molecular Biology Basic Medical College Xinjiang Medical University Urumqi 830054 Xinjiang Uygur Autonomous Region China

A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and polymerase chain reaction enzyme-linked immunosorbent assay results demonstrated that glial fibrillary acidic protein and telomerase expression increased gradually after injury, peaked at 28 days, and then gradually decreased. Spearman rank correlation showed a positive correlation between glial fibrillary acidic protein expression and telomerase expression in the glial scar. These results suggest that telomerase promotes glial scar formation.

关键词： spinal cord injury glial scar telomerase astrocytes glial fibrillary acidic protein

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telomerase Activity in Condyloma Acuminatum Tissue with Different HPV Types

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第2期22卷 171-173页

作者： TU Yating (涂亚庭) CHEN Shanjuan(陈善娟) FAN Chao(樊超) LIN Nengxing(林能兴) LIU Houjun(刘厚君) LIU Zhixiabg(刘志香) Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Department of Dermatology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022

Summary: The telomerse activity in condyloma acuminatum (CA) tissue with human papillomavirus (HPV) types of 6/11 and 16/18 was detected to investigate the function of telomerase in the occurrence, development and carcinogenesis of genital CA. Forty-two biopsies from patients with gennital CA and 30 control tissue samples were tested for telomerase activity, HPV presence and types. The telomerase activity was determined by modified telomerase repeat amplification protocol (TRAP) assay and HPV typing by polymerase chain reaction (PCR) with typing-specific primers. Results showed that HPV-DNA was negative and the expression rate of telomerase was 16.7 % in all normal skin samples. All CA samples were positive for HPV (6/11 type was found in 32 cases, 16/18 in 3 and mixed type in 7). telomerase activity was detectable in all CA patients. The telomerase activity in CA of 16/18 type was apparently higher than in CA of 6/11 type. It was concluded that the hyperplasia in CA might be increased as a result of HPV infection, suggesting that the activation of telomerase by HPV, especially by 16/18 type may play a role in the etiology and carcinogenesis of genital CA.

关键词： condyloma acuminatum human papillomavirus telomerase

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