Investigating the differential therapeutic efficacy and mechanisms of human umbilical cord mesenchymal stem cells at various passages in osteoarthritis treatment.

This study aimed to assess the clinical efficacy of umbilical cord mesenchymal stem cells (hUC-MSCs) from different passages (P3, P8, and P13) in the treatment of knee osteoarthritis (OA) and explore the underlying mechanisms. The hUC-MSCs from each passage were characterized and evaluated for their stemness, migration, proliferation, and marker expression. Rats with OA were treated with hUC-MSCs from each passage, and the therapeutic effects were assessed based on knee swelling, discomfort, and pathological examination of the knee joint. Co-culture experiments were conducted to examine the ability of hUC-MSCs to stimulate type II collagen synthesis and inhibit MMP13 expression in chondrocytes. Telomere length and telomerase activity of hUC-MSCs from each passage were measured to investigate the reasons for the observed differences in clinical efficacy. The results revealed that P3 and P8 hUC-MSCs exhibited superior osteogenic and chondrogenic differentiation potential compared to P13, while P13 demonstrated stronger adipogenic differentiation. The wound healing rate was significantly higher in the P3 and P8 groups compared to P13. All hUC-MSC groups expressed high levels of CD90 and CD105, indicating their mesenchymal stem cell characteristics, while CD31 and CD45 were not expressed. CD105 expression was significantly reduced in the P13 group. In the treatment of rat osteoarthritis, there were no significant differences in knee swelling, discomfort, Mankin scores, and pathological findings between P3 and P8 hUC-MSC treatments. However, there was a significant difference between the 8th and 13th passages. Co-culture experiments showed that hUC-MSCs from P3 and P8 enhanced type II collagen synthesis and reduced MMP13 expression in chondrocytes. Although no significant difference was observed between the P3 and P8 groups, a significant difference was found between the P13 and P8 groups. Telomere length analysis revealed that P13 samples had significantly shorter telomeres compared to both P3 and P8. The telomerase activity was positive in P3 and P8 hUC-MSCs, indicating no significant difference between these passages, while it was negative in P13 hUC-MSCs. In conclusion, P3 and P8 hUC-MSCs exhibited superior therapeutic potential for knee osteoarthritis compared to P13, possibly due to their enhanced differentiation capacity and telomerase activity.

Arctigenin from Fructus arctii Exhibits Antiaging Effects via Autophagy Induction, Antioxidative Stress, and Increase in Telomerase Activity in Yeast.

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called "senomorphics". In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

Evaluation of miR-130b-3p and miR-375 levels and telomere length with telomerase activity in prostate cancer.

Prostate cancer (PC) is the most frequent cancer in males, as well as the second highest cause of cancer-related deaths in men. Differences in expression levels of miRNAs were linked with prostat cancer pathogenesis. qPCR was used to evaluate the expression of miR-130b-3p and miR-375 in Benign Prostate Hyperplasia (BPH (n = 20) and PC (n = 22, pre- and post-operative) patients plasma. Relative telomere lengths (RLTs) in genomic DNA isolated from plasma were measured with qPCR, and telomerase activity analyzed by the ELISA method. PSA levels of PC patients were greater than of BPH patients (p = 0.0473). miR-130b-3p and miR-375 levels were significantly lower in pre-operative specimens of PC patients according to BPH (p = 0,0362, p = 0.0168, respectively). Similarly, post-operative miR-375 levels were lower in PC patients than in BPH patients (p = 0.1866). BPH patients had shorter RTLs than PC patients in both pre- (p=0.0438) and post-operative (p=0.0297) specimens. Telomerase activity was higher in PC patients than BPH(p = 0.0129). Interestingly, telomerase activity was further increased after surgery (p = 0.0003). We aim to identify the levels of miR-130b-3p and miR-375 expression and their relationship with telomerase activity in PC patients. Our data suggest that miRNAs and telomere length (TL) with telomerase activity may play a role in regulating prostate tumorgenesis and may be used as biomarkers for PC diagnosis.

A triggered DNA nanomachine with enzyme-free for the rapid detection of telomerase activity in a one-step method.

BACKGROUND: Telomerase is considered a biomarker for the early diagnosis and clinical treatment of cancer. The rapid and sensitive detection of telomerase activity is crucial to biological research, clinical diagnosis, and drug development. However, the main obstacles facing the current telomerase activity assay are the cumbersome and time-consuming procedure, the easy degradation of the telomerase RNA template and the need for additional proteases. Therefore, it is necessary to construct a new method for the detection of telomerase activity with easy steps, efficient reaction and strong anti-interference ability. RESULTS: Herein, an efficient, enzyme-free, economical, sensitive, fluorometric detection method for telomerase activity in one-step, named triggered-DNA (T-DNA) nanomachine, was created based on target-triggered DNAzyme-cleavage activity and catalytic molecular beacon (CMB). Telomerase served as a switch and extended few numbers of (TTAGGG)n repeat sequences to initiate the signal amplification in the T-DNA nanomachine, resulting in a strong fluorescent signal. The reaction was a one-step method with a shortened time of 1 h and a constant temperature of 37 °C, without the addition of any protease. It also sensitively distinguished telomerase activity in various cell lines. The T-DNA nanomachine offered a detection limit of 12 HeLa cells µL-1, 9 SK-Hep-1 cells µL-1 and 3 HuH-7 cells µL-1 with a linear correlation detection range of 0.39 × 102-6.25 × 102 HeLa cells µL-1 for telomerase activity. SIGNIFICANCE: In conclusion, our study demonstrated that the triggered-DNA nanomachine fulfills the requirements for rapid detection of telomerase activity in one-step under isothermal and enzyme-free conditions with excellent specificity, and its simple and stable structure makes it ideal for complex systems. These findings indicated the application prospect of DNA nanomachines in clinical diagnostics and provided new insights into the field of DNA nanomachine-based bioanalysis.

Telomerase activity and hTERT gene expression in patients with acute coronary syndrome and stable coronary artery disease.

BACKGROUND: In this study, we aimed to examine the telomerase activity and hTERT gene expression in patients with acute coronary syndrome (ACS) and those with stable coronary artery disease (SCAD) and compare the results to controls. Additionally, we compared overall mortality rates relative to the telomerase activity. METHODS: A total of 211 patients (78 ACS and 71 SCAD patients) were included in the study. The telomerase concentration was measured by ELISA and used to determine telomerase activity. The hTERT gene expression was determined by real-time PCR. RESULTS: The serum telomerase enzyme concentration was lower in ACS (36.61 ± 1.54) and SCAD (36.79 ± 1.57) when compared to the control group (37.03 ± 2.25). However, this difference did not reach statistical significance (p = 0.890). The hTERT gene expression acting in telomerase enzyme synthesis was 2.7-fold lower in ACS group (p = 0.070) and 2.2-fold lower in the SCAD group (p = 0.101) compared to the control group. Patients were followed for a median of 32 months (minimum: 0.1, maximum: 46.8). The serum telomerase concentrations in patients who died and those survived in the SCAD group (35.98 ± 2.02 vs 36.86 ± 1.52 ng/ml, respectively; p = 0.529) were similar to those in the ACS group (36.39 ± 1.08 vs 36.63 ± 1.60 ng/ml, respectively p = 0.993). CONCLUSIONS: In the current study, telomerase activity or hTERT expression was similar in patients with ACS, SCAD, and controls. Moreover, telomerase activity was not associated with all- cause mortality during the 32-month follow-up (Tab. 3, Fig. 1, Ref. 29).

LINC02454-CCT complex interaction is essential for telomerase activity and cell proliferation in head and neck squamous cell carcinoma.

Telomerase activity is upregulated in head and neck squamous cell carcinoma (HNSCC), yet its regulatory mechanisms remain unclear. Here, we identified a cancer-specific lncRNA (LINC02454) associated with poor prognosis by using LncRNA chip of our HNSCC cohorts and external datasets. Through employing negative-stain transmission electron microscopy (NS-TEM), we discovered an interaction between LINC02454 and CCT complex which would augment telomerase activity for maintaining telomere homeostasis. Supporting this, in the telomerase repeat amplification protocol (TRAP) assay and quantitative fluorescence in situ hybridization (Q-FISH) analysis, LINC02454 depletion significantly reduced telomerase activity and shortened telomere length. Consistently, pathways related to telomerase, mitosis, and apoptosis were significantly impacted upon LINC02454 knockdown in RNAseq analysis. Functionally, LINC02454-deficient cells exhibited a more significant senescence phenotype in ß-galactosidase staining, cell cycle, and apoptosis assays. We further confirmed the role of LINC02454 in HNSCC proliferation through a combination of in vitro and in vivo experiments. The therapeutic potential of targeting LINC02454 was verified by adenovirus-shRNA approach in HNSCC patient-derived xenograft (PDX) models. In summary, our findings provided valuable insights into the molecular mechanisms of HNSCC tumorigenesis and potential targets for future treatment modalities.

Measuring telomerase activity using TRAP assays.

Telomerase is a reverse transcriptase that consists of the telomerase reverse transcriptase (TERT) protein and the telomerase RNA component TERC which also harbors the template region for telomere synthesis. In its canonical function the enzyme adds single-stranded telomeric hexanucleotides de novo to the ends of linear chromosomes, telomeres, in telomerase-positive cells such as germline, stem- and cancer cells. This potential biochemical activity of telomerase can be measured with the help of a telomerase repeat amplification protocol (TRAP) which often includes a PCR amplification due to the low abundance of telomerase in most cells and tissues. The current chapter describes various TRAP methods to detect telomerase activity (TA) using gel-based methods, its advantages and deficits, how to perform an ELISA-based TRAP assay and how best to interpret its results. Since development of the TRAP assay in 1994, there have been numerous modifications and adaptations of the method from real-time PCR analysis, isothermal amplification and nanotechnology to CRISPR/Cas-based methods which will be briefly mentioned. However, it is not possible to cover all different TRAP methods and thus there is no comprehensiveness claimed by this chapter. Instead, the author describes various aspects of using TRAP assays including required controls, sample preparation, etc. in order to avoid pitfalls and set-backs in applying this rather complex and demanding technique. The TRAP assay is particularly important to support clinical diagnosis of cancer, analyze tumor therapy as well as to evaluate various approaches to inhibit TA as a form of anti-cancer therapy.

Telomerase activity and telomere length in women with breast cancer or without malignancy: A systematic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to assess whether telomerase activity and telomere length are associated with breast cancer. METHODS: PubMed, Web of Science, Embase, LILACS, Scielo, Embase, and CNKI databases were searched to obtain relevant articles published through May 10, 2023, following PRISMA guidelines and a registered PROSPERO protocol (CRD42022335402). We included observational studies reporting telomerase activity or telomere length in patients with breast cancer compared with women with benign lesions or normal tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I2 test was used to assess heterogeneity. RESULTS: The meta-analysis of telomerase shows significantly greater activity in patients with breast cancer than in those without malignancies (OR = 23.46, 95 % CI 14.07-39.11, p < 0.00001, I2 = 72 %). There were non-significant differences in relative telomere length (OR = 1.16, 95 % CI = 0.90-1.49, p = 0.26, I2 = 86 %) and leukocyte telomere length (OR = 2.32, 95 % CI = 0.89-6.08, p = 0.09, I2 = 98 %) between women with and without breast cancer. In subgroup analyses by world regions of studies, both telomerase activity and telomere length displayed the same trends as in their respective meta-analyses. In sensitivity analyses, variables showed their respective same trends. CONCLUSION: Telomerase activity is higher in patients with breast cancer than in women without malignancies. There were no significant differences in either relative telomere length or leukocyte telomere length in women with and without breast cancer. PROSPERO protocol CRD42022335402.

A target-triggered fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular telomerase activity.

Telomerase (TE) is a promising diagnostic and prognostic biomarker for many cancers. Quantification of TE activity in living cells is of great significance in biomedical and clinical research. Conventional fluorescence-based sensors for quantification of intracellular TE may suffer from problems of fast photobleaching and auto-fluorescence of some endogenous molecules, and hence are liable to produce false negative or positive results. To address this issue, a fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular TE was designed by functionalizing a bimetallic Au@Ag nanostructure with 4-p-mercaptobenzoic acid (internal standard SERS tag) and a DNA hybrid complex consisted of a telomerase primer strand and its partially complimentary strand modified with Rhodamine 6G. The bimetallic Au@Ag nanostructure serves as an excellent SERS-enhancing and fluorescence-quenching substrate. Intracellular TE will trigger the extension of the primer strand and cause the shedding of Rhodamine 6G-modified complimentary strand from the nano-system through intramolecular DNA strand displacement, resulting in the recovery of the fluorescence of Rhodamine 6G and decrease in its SERS signal. Both the fluorescence of R6G and the ratio between the SERS signals of 4-p-mercaptobenzoic acid and Rhodamine 6G can be used for in situ imaging of intracellular TE. Experimental results showed that the proposed nano-system was featured with low background, excellent cell internalization efficiency, good biocompatibility, high sensitivity, good selectivity, and robustness to false positive results. It can be used to distinguish cancer cells from normal ones, identify different types of cancer cells, as well as perform absolute quantification of intracellular TE, which endows it with great potential in clinical diagnosis, target therapy and prognosis of cancer patients.

A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

The application of quantitative telomerase activity measurement as an important indicator to monitor the cardiomyocyte differentiation process of human induced pluripotent stem cells under defined conditions.

The construction of an in vitro differentiation system for human induced pluripotent stem cells (hiPSCs) has made exciting progress, but it is still of great significance to clarify the differentiation process. The use of conventional genetic and protein-labeled microscopes to observe or detect different stages of hiPSC differentiation is not specific enough and is cumbersome and time-consuming. In this study, in addition to analyzing the expression of gene/protein-related markers, we used a previously reported simple and excellent quantitative method of cellular telomerase activity based on a quartz crystal microbalance (TREAQ) device to monitor the dynamic changes in cellular telomerase activity in hiPSCs during myocardial differentiation under chemically defined conditions. Finally, by integrating these results, we analyzed the relationship between telomerase activity and the expression of marker genes/proteins as well as the cell type at each study time point. This dynamic quantitative measurement of cellular telomerase activity should be a promising indicator for monitoring dynamic changes in a stage of hiPSC differentiation and inducing cell types. This study provided a quantitative, dynamic and simple monitoring index for the in vitro differentiation process of hiPSC-CMs, which was a certain reference value for the optimization and improvement of the induction system.

Thermal Preconditioning Alters the Stability of Hump-Snout Whitefish (Coregonus fluviatilis) and Its Hybrid Form, Showing Potential for Aquaculture.

One of the little-studied ways that climate warming or temperature increases in aquaculture could affect aquatic animals is through accelerated aging. This study is dedicated to understanding the principles of molecular and cellular aging in the target tissues of juvenile whitefishes (Yenisei hump-snout whitefish and its hybrid) under the influence of acute heat stress (up to 26 °C), and the effects of thermal preconditioning as pre-adaptation. Non-adapted stressed hump-snout whitefish showed a higher induction threshold for functionally active mitochondria in the blood and a decrease in telomerase activity in the liver after heat shock exposure as a long-term compensatory response to prevent telomere shortening. However, we observed heat-induced telomere shortening in non-adapted hybrids, which can be explained by a decrease in mitochondrial membrane stability and a gradual increase in energy demand, leading to a decrease in protective telomerase activity. The pre-adapted groups of hump-snout whitefish and hybrids showed a long-term or delayed response of telomerase activity to heat shock, which served as a therapeutic mechanism against telomere shortening. We concluded that the telomerase and telomere responses to thermal stress demonstrate plasticity of tolerance limits and greater stability in hump-snout whitefish compared with hybrids.

In Vitro Assessment of Gold Nanoparticles on Telomerase Activity and Telomere Length in Human Fibroblasts.

Telomerase activity coincides with lengthening of the ends of chromosomes known as telomeres. Telomere length is used as a marker for cellular aging. Telomeres shorten over time as cells divide, and certain bioactive compounds such as gold nanoparticles (AuNPs) may slow the shortening of telomeres by increasing telomerase activity. The objective of the present study is to assess the effect of AuNPs on telomerase activity and telomere length in human fibroblasts. Telomerase activity was measured using enzyme-linked immunosorbent assay (ELISA) in primary human lung fibroblasts (IMR90) and using quantitative PCR-based telomeric repeat amplification protocol (Q-TRAP) in primary human dermal fibroblasts, neonatal (HDFn). Telomere length was determined by Telomere Analysis Technology (TAT®)assay in HDFn. In IMR90, all AuNP treatments showed significant increases in telomerase activity when compared to earlier passages. HDFn treated with AuNPs at 0 ppm, 0.05 ppm, 0.5 ppm, or 5 ppm did not show significant differences in telomerase activity compared to the control group. Significant differences in telomere length in HDFn were observed at 2 weeks of 0.05 and 0.5 ppm AuNPs under oxidative culture conditions as compared to the control group. The study showed preliminary evidence that AuNPs may increase telomerase activity and decelerate the shortening of telomeres in human fibroblasts, suggesting its potential anti-aging effects, which warrants further investigation.

DNAzyme-Mediated Biodeposition Coupling Adjustable Cascade Electric Fields for Photoelectrochemical Telomerase Activity Monitoring.

Telomerase, as a specialized reverse transcriptase, plays a vital role in early cancer diagnostics and prognosis; thus, developing efficient sensing technologies is of vital importance. Herein, an innovative "signal-on-off" photoelectrochemical (PEC) sensing platform was developed for ultrasensitive evaluation of telomerase activity based on an electron-transfer tunneling distance regulation strategy and DNAzyme-triggerable biocatalytic precipitation. Concretely, cascade internal electric fields between CuInS2 quantum dots (QDs), graphitic carbon nitride nanosheets (g-C3N4 NSs), and TiO2 nanorod arrays (NRAs) were developed to realize cascade electron extraction and hole transfer. Enabled by such a design, an effective "signal-on" state to gain a progressively enhanced PEC output was designed by suppressing the photogenerated electron-hole pair recombination. With the introduction of hairpin probe H2 and the subsequent extension of the primer sequence driven by the target telomerase, the CuInS2 QDs labeled with hairpin probe H1 were programmatically unfolded, resulting in CuInS2 QDs' close proximity to the working electrode away from the cascade interface, accompanied by the formation of G-quadruplex/hemin complexes. The gradual undermining of tunneling distance and implantation of DNAzyme-initiating biocatalytic precipitation tremendously induced the sluggish migration kinetics of the photoinduced charge, accompanied by the photocurrent intensity decrement, leading to the "signal-off" state. Under optimized conditions, the as-prepared PEC biosensor realizes ultrasensitive detection of telomerase activity from 10 to 105 cell·mL-1 with a detection limitation of 3 cells·mL-1. As a proof of concept, this well-designed method provides new insights into signal amplification for telomerase activity evaluation and also presents promising potential for further development in drug screening, healthcare diagnostics, and biological assays.

Distinct roles of telomerase activity in age-related chronic diseases: An update literature review.

Although telomerase has low activity in somatic quiescent cells, it plays an significant roles in regenerative cells such as endothelial cells, hepatocytes, epithelial cells, and hemocytes. Telomerase activity and telomere length are critical factors in age-related chronic diseases as they are closely related to cell senescence. However, whether telomerase activity plays a key role in disease progression or whether the role of telomerase is unified among different diseases are unresolved. Considering that aging is the most important risk factor for neurodegenerative and metabolic diseases, this article will analyze the evidence, mechanism, and therapeutic potential of telomerase activity in several chronic disease, including type 2 diabetes, neurodegenerative diseases, atherosclerosis, heart failure and non-alcoholic fatty liver disease, in order to provide clues for the use of telomerase activity to target the treatment of age-related chronic diseases.

Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos.

Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.

Endometrial telomerase activity in women with either endometrial cancer or hyperplasia: A systematic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to assess whether endometrial telomerase activity is associated with endometrial cancer or hyperplasia. METHODS: PubMed, Web of Science, Embase, Scielo, LILAC, and CNKI databases were searched to obtain relevant literature for articles published through June 2022, following PRISMA guidelines and a registered PROSPERO protocol. We included observational studies reporting endometrial telomerase activity in patients with either endometrial cancer or hyperplasia compared with benign endometrial tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as the odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I2 test was used to assess heterogeneity. RESULTS: There were significant associations between endometrial telomerase activity and either endometrial cancer (20 studies, OR = 10.65, 95 % CI 6.39, 17.75, p = 0.00001, I2 = 21 %) or endometrial hyperplasia (nine studies, OR = 3.62, 95 % CI 1.61, 8.13, p = 0.002, I2 = 36 %) compared to women without endometrial cancer and hyperplasia. There was not a significant difference in telomerase activity in women with endometrial cancer compared to those with endometrial hyperplasia (seven studies, OR = 1.03; 95 % CI 0.31, 3.37, p = 0.96, I2 = 49 %). In subgroup analyses, there were no significant differences in telomerase activity in patients with endometrial cancer by type of observational studies and by countries of the studies. CONCLUSION: Endometrial telomerase activity is higher in women with either endometrial cancer or endometrial hyperplasia compared to control women without those lesions.

The Landscape of Telomere Length and Telomerase in Human Embryos at Blastocyst Stage.

The telomere length of human blastocysts exceeds that of oocytes and telomerase activity increases after zygotic activation, peaking at the blastocyst stage. Yet, it is unknown whether aneuploid human embryos at the blastocyst stage exhibit a different profile of telomere length, telomerase gene expression, and telomerase activity compared to euploid embryos. In present study, 154 cryopreserved human blastocysts, donated by consenting patients, were thawed and assayed for telomere length, telomerase gene expression, and telomerase activity using real-time PCR (qPCR) and immunofluorescence (IF) staining. Aneuploid blastocysts showed longer telomeres, higher telomerase reverse transcriptase (TERT) mRNA expression, and lower telomerase activity compared to euploid blastocysts. The TERT protein was found in all tested embryos via IF staining with anti-hTERT antibody, regardless of ploidy status. Moreover, telomere length or telomerase gene expression did not differ in aneuploid blastocysts between chromosomal gain or loss. Our data demonstrate that telomerase is activated and telomeres are maintained in all human blastocyst stage embryos. The robust telomerase gene expression and telomere maintenance, even in aneuploid human blastocysts, may explain why extended in vitro culture alone is insufficient to cull out aneuploid embryos during in vitro fertilization.

Angelica sinensis extract induces telomere dysfunction, cell cycle arrest, and mitochondria-mediated apoptosis in human glioblastoma cells.

Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12-15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.