Article
Psychology, Multidisciplinary
Nirodhi Namika Dasanayaka, Nirmala Dushyanthi Sirisena, Nilakshi Samaranayake
Summary: This study found associations between long-term meditation and telomere length, expression of hTERT and hTR genes, and methylation of the promoter region of hTERT gene. Meditators had longer telomeres, higher expression of hTERT and hTR genes, and lower methylation level of the promoter region of hTERT gene compared to non-meditators. These findings suggest that meditation as a lifestyle practice has multi-level beneficial effects on telomere dynamics, potentially promoting healthy aging.
FRONTIERS IN PSYCHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Golam Mustafa, Sajad Shiekh, G. C. Keshav, Sanjaya Abeysirigunawardena, Hamza Balci
Summary: The accessibility of telomeric DNA is influenced by its length, with longer telomeres forming more compact structures that are less accessible to binding molecules. Intermediate regions of telomeric DNA were found to be more accessible compared to the ends, suggesting a gradient of accessibility along the telomere length. These findings highlight the importance of telomere structure in regulating accessibility to critical genomic sites.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Nao Muraki, Mizuki Yamada, Hinako Doki, Riho Nakai, Kazuki Komeda, Daiki Goto, Nozomi Kawabe, Kohei Matsuoka, Miyoko Matsushima, Tsutomu Kawabe, Ichidai Tanaka, Masahiro Morise, Jerry W. W. Shay, John D. D. Minna, Mitsuo Sato
Summary: Mutant KRAS induces senescence in normal epithelial cells, preventing malignant transformation. This study investigates the mechanism of mutant KRAS-induced senescence in normal bronchial epithelial cells with upregulated telomerase and inactivation of the p16/RB pathway.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Substance Abuse
Fatemeh Zahra Darvishi, Mostafa Saadat
Summary: This study found that the mRNA levels of hTERT and TERF2 in cells treated with morphine decrease with increasing exposure time, but this alteration is reversible when morphine is removed from the culture medium. Additionally, there was no reduction in the relative expression of hTERT and TERF2 in cells co-treated with N-acetyl cysteine (NAC) and morphine.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Article
Cell Biology
Siyu Yan, Song Lin, Kexin Chen, Shanshan Yin, Haoyue Peng, Nanshuo Cai, Wenbin Ma, Zhou Songyang, Yan Huang
Summary: In this study, a compound called SC was found to have a dual function of down-regulating hTERT expression and directly affecting telomerase activity, making it an attractive candidate for anti-tumor therapy.
Article
Biochemistry & Molecular Biology
Darryl McLennan, Sonya K. Auer, Simon McKelvey, Lynn McKelvey, Graeme Anderson, Winnie Boner, Jessica S. Duprez, Neil B. Metcalfe
Summary: Restoring nutrients to streams can mitigate the adverse effects of habitat features on cellular ageing in fish. This suggests that increasing food supply through nutrient restoration reduces competition and stress levels in fish, ultimately improving their overall fitness.
Article
Biotechnology & Applied Microbiology
Chenjing Ma, Xian Li, Weifeng Ding, Xin Zhang, Hang Chen, Ying Feng
Summary: In this study, the effects of introducing exogenous hTERT on Periplaneta americana cells were investigated. It was found that hTERT expression promoted cell growth and extended cell lifespan by increasing telomerase activity and elongating telomeres. This suggests that introducing hTERT into insect cells could be an efficient method to establish certain insect cell lines.
Article
Biochemistry & Molecular Biology
Hugo Martin, Marie Doumic, Maria Teresa Teixeira, Zhou Xu
Summary: This study provides a mathematical description of the generation-dependent processes underlying non-terminal arrests in telomerase-negative cells. The research highlights differences in the mechanisms and states between non-terminal and terminal senescence arrests. The findings suggest that these two processes contribute to different consequences of senescence at the population level.
CELL AND BIOSCIENCE
(2021)
Review
Oncology
Gustavo Borges, Melanie Criqui, Lea Harrington
Summary: Telomere maintenance is crucial for the integrity of both normal and cancer cells. The instability of telomeres can lead to genome instability in cancer and aging, but cancer cells can partially overcome this instability by increasing telomerase expression.
MOLECULAR ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Barbara Jacczak, Blazej Rubis, Ewa Toton
Summary: The stability of telomeres is crucial for cell function, and research on telomere biology and telomerase activity has been of great interest in various medical and scientific fields. Maintaining optimal telomere length and telomerase activity is an important step in anti-aging strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Simon Toupance, Anne-Julie Fattet, Simon N. Thornton, Athanase Benetos, Jean-Louis Gueant, Isabelle Koscinski
Summary: Women's fertility is determined by the pool of ovarian follicles, which is influenced by telomere length and ovarian telomerase activity. Conditions like PCOS and POF may be correlated with differences in telomere length and telomerase activity, impacting fertility. Further research aims to explore stimulating ovarian telomerase to preserve the follicular pool without increasing cancer risk.
Article
Biochemistry & Molecular Biology
Atoll Goswami, Nafiul Huda, Tahirah Yasmin, Md. Ismail Hosen, A. K. M. Mahbub Hasan, A. H. M. Nurun Nabi
Summary: This study in Bangladeshi population found that patients with T2D have shorter telomeres compared to healthy individuals, and the genotype rs2853669 is associated with T2D. The research suggests that the TC genotype may have a protective role against the development of type 2 diabetes.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Immunology
Laureline Roger, Kelly Miners, Louise Leonard, Julia Grimstead, David Price, Duncan Baird, Kristin Ladell
Summary: This study used specific markers to separate different subsets of CD8+ memory T cells and measured their telomere lengths. The expression of CD45RA was found to be positively correlated with telomere length, while there was a disconnect between replicative history and cellular differentiation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chih-Yi Gabriela Lin, Anna Christina Naeger, Thomas Lunardi, Aleksandra Vancevska, Gerald Lossaint, Joachim Lingner
Summary: Telomere shortening can lead to diseases and aging, often due to the lack of telomerase in cells. By developing a new isolation protocol, specific proteins associated with telomere replication can be purified, revealing their importance for maintaining telomere stability. This study provides a valuable resource for understanding the dynamic changes of the telomeric proteome during replication.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Haihuan Lin, Juliane Mensch, Maria Haschke, Kathrin Jager, Brigitte Kottgen, Jens Dernedde, Evelyn Orso, Michael Walter
Summary: Establishing five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT demonstrated enhanced proliferative lifespan and reduced senescence signs, with growth increase and phenotype improvement independent of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for phenotype improvement, suggesting implications for therapeutic strategies in HGP and other premature aging syndromes.
Article
Biochemistry & Molecular Biology
Joshua Branter, Maria Estevez-Cebrero, Mohammed Diksin, Michaela Griffin, Marcos Castellanos-Uribe, Sean May, Ruman Rahman, Richard Grundy, Surajit Basu, Stuart Smith
Summary: The lack of treatment options for high-grade brain tumors has led to the exploration of alternative therapeutic modalities, including electrical field therapy. This study demonstrates the effectiveness of electric fields, delivered via TTFields or Deep Brain Stimulation (DBS), in inhibiting the viability of brain tumor cell lines. The study also uncovers potential mechanisms of action, with both treatments affecting cell cycle progression and showing interactions with mitochondrial functioning and endoplasmic reticulum stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Materials Science, Biomaterials
Ali Alazzo, Nurcan Gumus, Pratik Gurnani, Snjezana Stolnik, Ruman Rahman, Keith Spriggs, Cameron Alexander
Summary: Higher molar mass derivatives of poly(lysine) were found to yield smaller polyplexes with greater affinity for siRNA and higher transfection efficiency, although they may come with some cytotoxicity. Histidinylation improved biocompatibility slightly, but did not significantly enhance gene silencing efficiency compared to non-histidinylated derivatives.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Gareth Williams, David Chambers, Ruman Rahman, Francisco Molina-Holgado
Summary: By performing a transcriptional analysis of AM630 activity in different cell lines of glioblastoma, we found significant differences in gene expression profiles between core cells and invasive margin cells. Only the core cells expressed the potential target of AM630, the CB1 receptor, while the HTR2B serotonin receptor was moderately expressed in both cell types. Additionally, the AM630-driven transcriptional response was stronger in core cells, resulting in upregulation of immune response and downregulation of cell cycle and metastatic pathways.
Article
Pharmacology & Pharmacy
Phoebe McCrorie, Jonathan Rowlinson, David J. Scurr, Maria Marlow, Ruman Rahman
Summary: Historically, pre-clinical neuro-oncological drug delivery studies have primarily relied on overall animal survival as a measure of efficacy. However, this study demonstrates the potential of OrbiSIMS, a next-generation analytical instrument, to accurately detect brain penetration of drug compounds and provide imaging capabilities. This method could complement in vivo efficacy studies and assess the distribution and penetration of drugs in the brain.
Article
Multidisciplinary Sciences
Claudio Tomi-Andrino, Alina Pandele, Klaus Winzer, John King, Ruman Rahman, Dong-Hyun Kim
Summary: The heterogeneity of cancer hampers the development of universal cancer treatments, requiring tailored therapies for each type of cancer. Reprogramming cellular metabolism is seen as a potential source of drug targets. More strategies are needed to reduce and prioritize the list of potential candidates for drug repurposing.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
James Wood, Salah Abdelrazig, Sergey Evseev, Catherine Ortori, Marcos Castellanos-Uribe, Sean T. May, David A. Barrett, Mohammed Diksin, Sajib Chakraborty, Dong-Hyun Kim, Richard G. Grundy, Ruman Rahman
Summary: High-grade gliomas are aggressive cancers that require cholesterol for their energy needs. The drug LXR-623 can reduce the levels of cholesterol inside cancer cells and impair their growth. This research provides evidence for using LXR-623 to test its effectiveness in increasing the survival of mice with high-grade gliomas.
Article
Pharmacology & Pharmacy
Paula Muresan, Phoebe McCrorie, Fiona Smith, Catherine Vasey, Vincenzo Taresco, David J. Scurr, Stefanie Kern, Stuart Smith, Pavel Gershkovich, Ruman Rahman, Maria Marlow
Summary: This study developed polymeric microneedle (MN) patches for the treatment of CNS tumors. The results demonstrated successful drug release and penetration, providing a potential solution for local brain drug delivery.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Review
Oncology
Ruman Rahman, Miroslaw Janowski, Clare L. Killick-Cole, William G. B. Singleton, Emma Campbell, Piotr Walczak, Soumen Khatua, Lukas Faltings, Marc Symons, Julia R. Schneider, Kevin Kwan, John A. Boockvar, Steven S. Gill, J. Miguel Oliveira, Kevin Beccaria, Alexandre Carpentier, Michael Canney, Monica Pearl, Gareth J. Veal, Lisethe Meijer, David A. Walker
Summary: Brain tumors are the leading cause of cancer deaths in children and young adults, but drug treatments have had limited success due to the blood-brain barrier. This review explores techniques to enhance drug delivery to brain tumors and discusses preclinical models for translational development. It also highlights the potential of existing approved drugs when combined with efficient delivery methods. This research aims to address the current challenges faced by children with brain tumors and improve treatment outcomes.
Article
Chemistry, Analytical
Wenshi He, Max K. Edney, Simon M. L. Paine, Rian L. Griffiths, David J. Scurr, Ruman Rahman, Dong-Hyun Kim
Summary: This study used the OrbiSIMS technique to investigate the metabolism of brain tumors within their highly heterogeneous microenvironment. The results showed that OrbiSIMS could differentiate morphologically distinct regions within single tumors. Cancer cells from necrotic regions were separated from viable GBM cells based on specific metabolites. In addition, tryptophan metabolism was discovered to be essential for GBM cellular survival. This study demonstrates the potential of OrbiSIMS for understanding tumor heterogeneity and developing targeted therapies.
ANALYTICAL CHEMISTRY
(2023)
Article
Nanoscience & Nanotechnology
Paula Muresan, Stephen Woodhams, Fiona Smith, Vincenzo Taresco, Jaymin Shah, Mei Wong, Victoria Chapman, Stuart Smith, Gareth Hathway, Ruman Rahman, Pavel Gershkovich, Maria Marlow
Summary: We investigated the biodistribution of cannabidiol (CBD) in the central nervous system (CNS) and found that both an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs) were preferentially retained in the spinal cord, with high concentrations reaching the brain within a short time. The CBD nanoemulsion showed faster brain delivery than the CBD PCNPs, with higher retention in the brain. Both formulations exhibited immediate anti-nociceptive effects.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Claudia Martins, Marco Araujo, Alessio Malfanti, Catarina Pacheco, Stuart J. J. Smith, Bernard Ucakar, Ruman Rahman, Jonathan W. W. Aylott, Veronique Preat, Bruno Sarmento
Summary: Report the development of hypothesis-driven stimuli-responsive nanoparticles (NPs) for glioblastoma (GBM) therapy. These NPs have multifunctional features that overcome the insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting, two major challenges in anti-GBM treatments. In preclinical studies, the stimuli-responsive NPs effectively targeted GBM cells, enhanced cell uptake, increased cytotoxicity, improved BBB permeability, and demonstrated antitumor efficacy in GBM models.
Article
Pharmacology & Pharmacy
Adenike O. Adekeye, David Needham, Ruman Rahman
Summary: This study determined LDL receptor (LDLR) expression in high grade gliomas (HGGs) using immunohistochemistry and confirmed its potential as a therapeutic target. The study also analyzed LDLR expression levels in three cell line models, confirming their suitability for testing LDLR-targeted nanoparticle uptake, retention, and cytotoxicity.
Article
Genetics & Heredity
Geoffroy Andrieux, Tonmoy Das, Michaela Griffin, Jakob Straehle, Simon M. L. Paine, Juergen Beck, Melanie Boerries, Dieter H. Heiland, Stuart J. Smith, Ruman Rahman, Sajib Chakraborty
Summary: The study investigated the cell population responsible for 5-aminolevulinic acid (5ALA) metabolism and its role in GBM recurrence. The presence of these cells can serve as an early indicator of recurrence and studying their molecular and cellular features can lead to more effective treatments to delay or block GBM recurrence.
Article
Materials Science, Biomaterials
Cara Moloney, Fatemeh Mehradnia, Robert J. Cavanagh, Asmaa Ibrahim, Amanda K. Pearce, Alison A. Ritchie, Philip Clarke, Ruman Rahman, Anna M. Grabowska, Cameron Alexander
Summary: The therapeutic effectiveness of nanomedicines depends on their access to target sites in the body, which is affected by their size, shape, and transport properties. Designing nanomaterials with optimal physicochemical properties for in vivo efficacy remains a challenge.
BIOMATERIALS SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Vincenzo Taresco, Thais F. Abelha, Robert J. Cavanagh, Catherine E. Vasey, Akosua B. Anane-Adjei, Amanda K. Pearce, Patricia F. Monteiro, Keith A. Spriggs, Philip Clarke, Alison Ritchie, Stewart Martin, Ruman Rahman, Anna M. Grabowska, Marianne B. Ashford, Cameron Alexander
Summary: Amphiphilic block co-polymers can assemble into nanoparticles with different sizes and structures, affecting the internalization rate and cytotoxicity towards breast cancer cells, with the BAB blocks accumulating most in the lungs and liver. Nanoparticles generated by conjugating doxorubicin show higher cytotoxicity compared to the free drug.
ADVANCED THERAPEUTICS
(2021)