Methylation, Gene Expression, and Risk Genotypes at the TERT-CLPTM1L Locus in Cervical Cancer.

The reverse transcriptase subunit of telomerase, TERT, is frequently activated in high-grade dysplasia and invasive cancers of the uterine cervix. Telomerase activation through hypomethylation of the TERT promoter holds promise as a biomarker for cervical cancer progression, however, specific CpG sites involved in cervical cancer risk remain to be fully defined. A recent genome-wide association study on cervical cancer identified genetic polymorphisms at 5p13.33 (close to TERT-CLPTM1L) but the underlying mechanisms are undetermined. We investigated 529 CpG sites within the TERT promoter region and 3 CpG islands nearby, and 21 CpG sites within CLPTM1L in 190 bisulfite-converted cervical tumor DNA samples from BioRAIDs (NCT02428842). We identified eight CpG sites within TERT intron 2 where methylation was significantly associated with the genotypes of cervical cancer risk variants rs27070 and rs459961 in cervical tumors after multiple testing correction (p < 9.4 × 10E-5). Hypermethylation at chr5:1289663 correlated with decreased TERT mRNA levels. In an independent series of 188 normal or dysplastic cervical tissues, rare alleles of rs27070 and rs459961 were associated with low basal CLPTM1L levels and with the absence of TERT mRNA in HPV-negative samples, consistent with their proposed role as protective variants for cervical cancer. HPV infection was associated with increased CLPTM1L and TERT levels. Collectively, our results provide a link between cervical cancer risk variants, methylation, and gene expression and implicate both TERT and CLPTM1L as genes modulated by genomic background and HPV infection during cervical cancer development.

Simultaneous imaging of telomerase activity and protein tyrosine kinase 7 in living cells during epithelial-mesenchymal transformation via a near-infrared light-activatable nanoprobe.

Exploring the relationship between key regulation molecules (such as telomerase and protein tyrosine kinase 7) during epithelial-mesenchymal transformation of cells is beneficial for studying malignant tumor metastasis. Fluorescence is usually used for real-time monitoring the distribution and expression of regulatory molecules in living cells. However, the recognition function of these classical nanoprobes is "always active" due to the absence of exogenous control, which leads to the amplification of both the background signal and the response signal, making it difficult to distinguish changes in biomolecule expression levels. To improve the fluorescence ratio between tumor and normal cells, we constructed near-infrared light-activatable nanoprobes by engineering the functional units of catalytic hairpin assembly and integrating upconversion luminescence nanoparticles. Under near-infrared light irradiation, the nanoparticles, serving as a near-infrared-to-ultraviolet light transducer, induced the photolysis of the photo-cleavable linkers sealed in hairpins. The recognition function of the nanoprobes can be controlled by near-infrared light, preventing them from recognizing the targets in non-irradiated regions. By employing the nanoprobes, we realized simultaneous imaging of two regulatory molecules in living cells and observed an increase in telomerase activity and a decrease in protein tyrosine kinase 7 expression during drug-induced epithelial-mesenchymal transformation. This work provides a promising method for revealing changes and relationships of regulatory molecules during tumor metastasis.

Exercise to combat cancer: focusing on the ends.

Cancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy has improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off target side-effects that must be addressed before they reach clinical practice. Regular exercise training is associated with telomerase-mediated telomere maintenance in healthy cells, which is associated with healthy ageing. A single bout of endurance exercise training dynamically, but temporarily, increases TERT mRNA and telomerase activity, as well as several molecules that control genomic stability and telomere length (i.e., shelterin and TERRA). Considering the epidemiological findings and accumulating research highlighting that exercise significantly reduces the risk of many types of cancers and the anti-carcinogenic effects of exercise on tumour growth in vitro, investigating the governing molecular mechanisms of telomerase control in context with exercise and cancer may provide important new insights to explain these findings. Specifically, the molecular mechanisms controlling telomerase in both healthy cells and tumours after exercise could reveal novel therapeutic targets for tumour-specific telomere maintenance and offer important evidence that could refine current physical activity and exercise guidelines for all stages of cancer care.

Deciphering the impact of TERT/telomerase on immunosenescence and T cell revitalization.

Immunosenescence impacts both the innate and adaptive immune systems, predominantly affecting certain immune cell types. A notable manifestation of immunosenescence is the diminished efficacy of adaptive immunity. The excessive senescence of immune cells, particularly T cells, leads to marked immune deficiency, consequently escalating the risk of infections, tumors, and age-associated disorders. Lymphocytes, especially T cells, are subject to both replicative and premature senescence. Telomerase reverse transcriptase (TERT) and telomerase have multifaceted roles in regulating cellular behavior, possessing the ability to counteract both replicative and premature senescence in lymphocytes. This review encapsulates recent advancements in understanding immunosenescence, with a focus on T cell senescence, and the regulatory mechanisms involving TERT/telomerase. Additionally, it comprehensively discusses strategies aimed at inhibiting immunosenescence by augmenting TERT/telomerase activity.

An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction.

A discrete mathematical model based on ordinary differential equations and the associated continuous model formed by a partial differential equation, which simulate the generational and temporal evolution of a stem cell population, are proposed. The model parameters are the maximum proliferation potential and the rates of mitosis, death events and telomerase activity. The mean proliferation potential at each point in time is suggested as an indicator of population aging. The model is applied on hematopoietic stem cells (HSCs), with different telomerase activity rates, in a range of variation of maximum proliferation potential in healthy individuals, to study the temporal evolution of aging. HSCs express telomerase, however not at levels that are sufficient for maintaining constant telomere length with aging [1,2]. Women with primary ovarian insufficiency (POI) are known to have low telomerase activity in granulosa cells and peripheral blood mononuclear cells [3]. Extrapolating this to hematopoietic stem cells, the mathematical model shows the differences in proliferation potential of the cell populations when telomerase expression is activated using sexual steroids, though the endogenous promoter or with gene therapy using exogenous, stronger promoters within the adeno-associated virus. In the first case, proliferation potential of cells from POI condition increases, but when adeno-associated viruses are used, the proliferation potential reaches the levels of healthy cell populations.

Muti-target rationale design of novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates as telomerase/JAK1/STAT3/TLR4 inhibitors: In vitro and in vivo investigations.

In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem. Therefore, novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates (4a-n) were synthesized. Applying the lead optimization strategy of the previously designed compound 8e; compound 4l showed an improved telomerase inhibition of 64.95 % and a superior growth inhibition of 79 % suggesting its potential use as a successful "multitarget-directed drug" for cancer therapy. Accordingly, compound 4l was further selected to evaluate its additional JAK1/STAT3/TLR4 inhibitory potentials. Compound 4l represented a very promising JAK1 inhibitory potential with a 0.46-fold change, compared to that of pacritinib reference standard (0.33-fold change). Besides, it showed a superior STAT3-inhibitory potential with a 0.22-fold change compared to sorafenib (0.33-fold change). Additionally, compound 4l downregulated TLR4 protein expression by 0.81-fold change compared to that of resatorvid (0.29-fold change). Also, molecular docking was performed to investigate the binding mode and affinity of the superior candidate 4l towards the four target receptors (telomerase, JAK1, STAT3, and TLR4). Furthermore, the therapeutic potential of compound 4l as an antitumor agent was additionally explored through in vivo studies involving female mice implanted with Solid Ehrlich Carcinoma (SEC). Remarkably, compound 4l led to prominent reductions in tumor size and mass. Concurrent enhancements in biochemical, hematologic, histopathologic, and immunohistochemical parameters further confirmed the suppression of angiogenesis and inflammation, elucidating additional mechanisms by which compound 4l exerts its anticancer effects.

The Impact of Ten Days of Periodic Fasting on the Modulation of the Longevity Gene in Overweight and Obese Individuals: A Quasi-Experimental Study.

BACKGROUND: Fasting potentially alters the aging process induced by obesity by regulating telomere integrity, which is related to longevity genes. However, the impact of periodic fasting (PF) on the expression of longevity genes, particularly Forkhead Box O Transcription Factors (FOXO3a) and the Human Telomerase Reverse Transcriptase (hTERT), is not fully understood. This study aimed to analyze the effects of PF, specifically on FOXO3a, hTERT expression, and other associated factors. METHODS: A quasi-experimental 10-day study was conducted in Surabaya, East Java, Indonesia. This study consisted of an intervention group (PFG), which carried out PF for ten days using a daily 12 h time-restricted eating protocol, and a control group (CG), which had daily meals as usual. FOXO3a and hTERT expression were analyzed by quantitative real-time qPCR. A paired t-test/Wilcoxon test, independent t-test/Mann-Whitney U-test, and Spearman's correlation test were used for statistical analysis. RESULT: Thirty-six young men participated in this study. During the post-test period, FOXO3a expression in the PFG increased 28.56 (±114.05) times compared to the pre-test, but the difference was not significant. hTERT expression was significantly higher in both the CG and PFG. The hTERT expression in the PFG was 10.26 (±8.46) times higher than in the CG, which was only 4.73 (±4.81) times higher. There was also a positive relationship between FOXO and hTERT in the CG. CONCLUSIONS: PF significantly increased hTERT expression in the PFG; however, no significant increase was found in FOXO3a expression. PF regimens using the 12 h time-restricted eating approach may become a potential strategy for preventing obesity-induced premature aging by regulating longevity gene expression.

The Impact of Extensive Surgical Resection of Butterfly Glioblastomas on Outcomes in the Presence of TERT Mutation and EGFR Amplification: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: This study aimed to assess if extensive surgical resection enhances outcomes in wild-type Isocitrate Dehydrogenase (IDH) butterfly glioblastoma (B-GBM) patients, despite the presence of Telomerase Reverse Transcriptase (TERT) mutation and Epidermal Growth Factor Receptor (EGFR) amplification. METHODS: The study, retrospectively conducted from 2014 to 2022, involved 723 GBM patients, 41 of whom met the criteria for IDH wild-type B-GBM. Exclusion criteria comprised prior diagnoses or treatments for low-grade glial tumors. Surgeons, employing two approaches-partial and extensive surgery-categorized patients based on age, sex, tumor location, corpus callosum involvement, and genetic characteristics. The interval between initial surgery and tumor recurrence/tumor-free period (TR/TFP) and overall survival (OS) were recorded and compared between the partial and extensive resection groups, analyzing the impact of resection width on TR/TFP and OS. Preoperative assessments utilized thin-section cranial computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI). Intraoperatively, tumor excision was guided by sodium fluorescein, and margins were delineated via neuronavigation. Genetic alterations (TERT mutations and EGFR amplifications) were correlated with surgical type, TR/TFP, and OS. Karnofsky Performance Scale (KPS) evaluations were performed pre- and post-operatively and at key intervals, comparing outcomes between surgical groups. Standard radiotherapy and chemotherapy regimens were administered to all patients. RESULTS: Extensive resection yielded significantly longer TR/TFP compared to partial resection, despite TERT gene mutation and EGFR amplification being linked to shorter TR/TFP and OS. Its impact on OS, however, was not significant. KPS scores indicated a superior quality of life after extensive resection, with sustained improvement upon recurrence. CONCLUSIONS: Extensive resection of B-GBM, even in the presence of adverse genetic alterations, may prolong TR/TFP, offering patients a period of improved comfort with minimal distress.

Anti-aging based on stem cell therapy: A scoping review.

Stem cells are present in the tissues and organs and remain in a quiescent and undifferentiated state until it is physiologically necessary to produce new descendant cells. Due to their multipotency property, mesenchymal stem cells have attracted considerable attention worldwide due to their immunomodulation and therapeutic function in tissue regeneration. Stem cells secrete components such as paracrine factors, extracellular vesicles, and exosomes which have been shown to have anti-inflammatory, anti-aging, reconstruction and wound healing potentials in many in vitro and in vivo models. The pluripotency and immunomodulatory features of stem cells could potentially be an effective tool in cell therapy and tissue repair. Aging affects the capacity for self-renewal and differentiation of stem cells, decreasing the potential for regeneration and the loss of optimal functions in organisms over time. Current progress in the field of cellular therapy and regenerative medicine has facilitated the evolution of particular guidelines and quality control approaches, which eventually lead to clinical trials. Cell therapy could potentially be one of the most promising therapies to control aging due to the fact that single stem cell transplantation can regenerate or substitute the injured tissue. To understand the involvement of stem cells not only in tissue maintenance and disease but also in the control of aging it is important to know and identify their properties, functions, and regulation in vivo, which are addressed in this review.

Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.

Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.

Analysis of the clonal origin and differences in the biological behavior of multifocal papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) exhibits a trend of multifocal growth. However, the clonal origin of multiple cancer foci in the thyroid gland remains an issue of ongoing debate. In order to investigate the clonal origin and biological behavior differences of multifocal PTC (MPTC) from a unique perspective, a combination of dual gene and dual protein detection methods was used. The present study included 52 patients with MPTC. Immunohistochemical staining was used to assess the expression of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and telomerase reverse transcriptase (TERT) proteins, while quantitative PCR and Sanger sequencing were used to identify BRAF and TERT gene mutations. Based on the results, MPTC cases were classified into two clonal origins, namely intraglandular metastatic (71.2%) and independent multicentric origin (28.8%). BRAF protein expression and BRAF gene mutation were significantly higher in the intraglandular metastasis group than in the multicentric cancer group. However, no significant differences in TERT protein expression and TERT gene mutation were observed between the two groups. Sex, central lymph node metastasis rate, Hashimoto's thyroiditis and tumor distribution laterality were not found to differ significantly between the two groups. However, significant differences were detected in age at initial diagnosis, lateral cervical lymph node metastasis rate, tumor capsule invasion rate and maximum tumor diameter. The study found that MPTC predominantly occurs due to intraglandular metastasis, which is associated with stronger tumor invasiveness than cancer foci with multiple independent origins, as it is more likely to exhibit pathogenic gene mutations and abnormal protein expression, cervical lymph node metastasis and capsule invasion. Therefore, it is recommended that the surgical approaches and follow-up strategies for intraglandular metastatic MPTC should be aggressive and individualized.

Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.

There are few convincing studies establishing the relationship between endogenous factors that cause obesity, cellular aging, and telomere shortening. Without a functional telomerase, a cell undergoing cell division has progressive telomere shortening. While obesity influences health and longevity as well as telomere dynamics, cellular senescence is one of the major drivers of the aging process and of age-related disorders. Oxidative stress induces telomere shortening, while decreasing telomerase activity. When progressive shortening of telomere length reaches a critical point, it triggers cell cycle arrest leading to senescence or apoptotic cell death. Telomerase activity cannot be detected in normal breast tissue. By contrast, maintenance of telomere length as a function of human telomerase is crucial for the survival of breast cancer cells and invasion. Approximately three-quarters of breast cancers in the general population are hormone-dependent and overexpression of estrogen receptors is crucial for their continued growth. In obesity, increasing leptin levels enhance aromatase messenger ribonucleic acid (mRNA) expression, aromatase content, and its enzymatic activity on breast cancer cells, simultaneously activating telomerase in a dose-dependent manner. Meanwhile, applied anti-estrogen therapy increases serum leptin levels and thus enhances leptin resistance in obese postmenopausal breast cancer patients. Many studies revealed that shorter telomeres of postmenopausal breast cancer have higher local recurrence rates and higher tumor grade. In this review, interlinked molecular mechanisms are looked over between the telomere length, lipotoxicity/glycolipotoxicity, and cellular senescence in the context of estrogen receptor alpha-positive (ERα+) postmenopausal breast cancers in obese women. Furthermore, the effect of the potential drugs, which are used for direct inhibition of telomerase and the inhibition of human telomerase reverse transcriptase (hTERT) or human telomerase RNA promoters as well as approved adjuvant endocrine therapies, the selective estrogen receptor modulator and selective estrogen receptor down-regulators are discussed.

Telomerase reverse transcriptase protects against diabetic kidney disease by promoting AMPK/PGC-1a-regulated mitochondrial energy homeostasis.

Disordered glucose and lipid metabolism, coupled with disturbed mitochondrial bioenergetics, are pivotal in the initiation and development of diabetic kidney disease (DKD). While the essential role of telomerase reverse transcriptase (TERT) in regulating mitochondrial function in the cardiovascular system has been recognized, its specific function in maintaining mitochondrial homeostasis in DKD remains unclear. This study aimed to explore how TERT regulates mitochondrial function and the underlying mechanisms. In vitro, human renal proximal tubular HK-2 cells exposed to high glucose/high fat (HG/HF) presented significant downregulation of TERT and AMPK dephosphorylation. This led to decreased ATP production, altered NAD+/NADH ratios, reduced mitochondrial complex activities, increased mitochondrial dysfunction, lipid accumulation, and reactive oxygen species (ROS) production. Knockdown of TERT (si-TERT) further exacerbated mitochondrial dysfunction, decreased mitochondrial membrane potential, and lowered levels of cellular oxidative phosphorylation and glycolysis, as determined via a Seahorse X24 flux analyzer. Conversely, mitochondrial dysfunction was significantly alleviated after pcDNA-TERT plasmid transfection and adeno-associated virus (AAV) 9-TERT gene therapy in vivo. Notably, treatment with an AMPK inhibitor, activator, and si-PGC-1a (peroxisome proliferator-activated receptor γ coactivator-1α), resulted in mitochondrial dysfunction and decreased expression of genes related to energy metabolism and mitochondrial biogenesis. Our findings reveal that TERT protects mitochondrial function and homeostasis by partially activating the AMPK/PGC-1a signaling pathway. These results establish a crucial foundation for understanding TERT's critical role inmitochondrial regulation and its protective effect on DKD.

Telomeres and telomerase in Sarcoma disease and therapy.

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Electroacupuncture Ameliorates Neuronal Damage and Neurological Deficits after Cerebral Ischemia-Reperfusion Injury via Restoring Telomerase Reverse Transcriptase.

The purpose of this study is to identify the therapeutic effect of electroacupuncture (EA) on cerebral ischemia-reperfusion (I/R) injury, and to clarify the regulatory mechanism related to telomerase reverse transcriptase (TERT)-mediated telomerase activity. A Middle cerebral artery occlusion/reperfusion (MCAO/R) animal model was constructed and rats were treated by EA invention at the Baihui (GV20) and Fengchi (GB20) acupoints. Neurological deficits were assessed via rotarod test and Morris water maze test. 2,3,5-Triphenyltertrazolium chloride (TTC) staining was performed to evaluate infarct volume. Histological changes were observed under H&E staining and Nissl staining. TERT expression was examined using qRT-PCR and western blot. Telomerase activity was assessed with TRAP method. Neuron apoptosis and senescence were assessed by TUNEL and immunofluorescence assays. Inflammatory cytokines and oxidative stress-indicators were examined using commercial kits. EA intervention at both GV20 and GB20 acupoints reduced infarct volumes (2.48 ± 1.89 vs. 29.56 ± 2.55), elevated the telomerase activity (0.84 ± 0.08 vs. 0.34 ± 0.09), and upregulated the levels of total TERT protein (0.61 ± 0.09 vs. 0.21 ± 0.05) and mitochondrial TERT (Mito-TERT; 0.54 ± 0.03 vs. 0.27 ± 0.03) in hippocampus tissues of MCAO/R rats. EA intervention attenuated motor dysfunction (112.00 ± 6.69 vs. 30.02 ± 2.60) and improved spatial learning (23.87 ± 1.90 vs. 16.23 ± 1.45) and memory ability (8.38 ± 1.06 vs. 4.13 ± 1.13) of rats with cerebral I/R injury. In addition, EA intervention significantly attenuated histopathological changes of injured neurons, mitigated neuron apoptosis (32.27 ± 5.52 vs. 65.83 ± 4.31) and senescence in MCAO/R rats, as well as inhibited excessive production of inflammatory cytokines and attenuated oxidative stress. However, the above therapeutic efficiency of EA intervention in MCAO/R rats was partly eliminated by TERT knockdown. EA intervention at GB20 and GV20 acupoints exerted a protective role in cerebral I/R injury partly through restoring TERT function, implying the clinical potential of EA treatment in the treatment of ischemic stroke.

Leishmania major telomerase RNA knockout: From altered cell proliferation to decreased parasite infectivity.

This study focuses on the biological impacts of deleting the telomerase RNA from Leishmania major (LeishTER), a parasite responsible for causing leishmaniases, for which no effective treatment or prevention is available. TER is a critical player in the telomerase ribonucleoprotein complex, containing the template sequence copied by the reverse transcriptase component during telomere elongation. The success of knocking out both LeishTER alleles was confirmed, and no off-targets were detected. LmTER-/- cells share similar characteristics with other TER-depleted eukaryotes, such as altered growth patterns and partial G0/G1 cell cycle arrest in early passages, telomere shortening, and elevated TERRA expression. They also exhibit increased γH2A phosphorylation, suggesting that the loss of LeishTER induces DNA damage signaling. Moreover, pro-survival autophagic signals and mitochondrion alterations were shown without any detectable plasma membrane modifications. LmTER-/- retained the ability to transform into metacyclics, but their infectivity capacity was compromised. Furthermore, the overexpression of LeishTER was also deleterious, inducing a dominant negative effect that led to telomere shortening and growth impairments. These findings highlight TER's vital role in parasite homeostasis, opening discussions about its potential as a drug target candidate against Leishmania.

Boehmeria Nivea Extract (BNE-RRC) Reverses Epithelial-Mesenchymal Transition and Inhibits Anchorage-Independent Growth in Tumor Cells.

The epithelial-mesenchymal transition (EMT) phenotype, identified as a significant clinical indicator in regard to cancer, manifests as a biological process wherein cells transition from having epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responses to various types of tissue damage. This study investigated the impact of BNE-RRC on oral cancer cells (KB) and revealed its significant effects on cancer cell growth, migration, invasion, and the EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing the EMT to a mesenchymal-epithelial transition (MET). Extraordinarily, sustained culturing of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting that BNE-RRC is a potential therapeutic agent for cancer. These findings highlight the promise of BNE-RRC as a comprehensive therapeutic agent for cancer treatment that acts by inhibiting cancer cell growth, migration, and invasion while also orchestrating a reversal of the EMT process. In this study, we propose that BNE-RRC could be an effective agent for cancer treatment.

Telomere dynamics as mediators of gut microbiota-host interactions.

The highly proliferative gut tissue exhibits rapid telomere shortening with systemic effects on the host organism. Recent studies have demonstrated a bidirectionality in interactions between intestinal telomere length dynamics and the composition and activity of the gut microbiome thus linking processes of inflammation, dysbiosis and aging across different vertebrate species.

GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba.

The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.