Molecular Biology Reports最新文献

The genus Artemisia (family Asteraceae) is widely recognized for its medicinal properties, among which artemisinin is the most notable, historically serving as a key antimalarial agent. Accumulating evidence now highlights the significant anticancer potential of Artemisia species, with bioactive compounds such as artemisinin and its derivatives exhibiting promising activity across multiple cancer types. This review provides a comprehensive overview of the molecular mechanisms underlying the anticancer effects of Artemisia-derived compounds, including apoptosis induction, cell cycle arrest, and oxidative stress modulation. In addition, it examines their therapeutic efficacy in preclinical in vivo models and summarizes findings from early-phase clinical trials. Despite encouraging preclinical results, challenges such as drug resistance, limited bioavailability, and barriers to clinical translation remain.

Telomere maintenance has been portrayed primarily as a problem of DNA-protein architecture and chromatin control, yet a complementary layer has been revealed at the level of RNA chemistry. In this Review, RNA modifications and their writer-reader-eraser and RNA-editing systems are integrated into a framework for chromosome-end homeostasis. Epitranscriptomic regulation of the telomerase ribonucleoprotein is examined, and assembly, activity, and recruitment are shown to be reshaped by chemical marks on TERC, specialized RNA capping, and processing pathways. Telomeric transcripts, particularly TERRA, are discussed as modified substrates whose stability, trafficking, and propensity for telomeric RNA: DNA hybrid formation can be tuned by RNA marks and their readers. Downstream consequences for replication stress, DNA damage signaling, and recombination-driven alternative lengthening of telomeres are summarized, together with emerging examples in which modification of telomere-factor mRNAs has been linked to rewiring of maintenance networks. Across these themes, links to telomeropathies, aging-associated inflammation, environmental stressors, and cancer are collated to connect mechanism to phenotype. Experimental bottlenecks and opportunities-site-resolved mapping, locus-targeted editing, and pharmacologic modulation of RNA-modifying enzymes-are outlined as routes toward causal models and therapeutic utilization.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) has emerged as a significant focus in cancer research due to its dual functionality as both an inhibitor of matrix metalloproteinases and a multifunctional cytokine. Recent studies underscore the pivotal role of TIMP-1 in extracellular matrix remodeling, a process essential for tumor progression and metastasis. Moreover, TIMP-1 performs a variety of functions within the tumor microenvironment that extend beyond its traditional protease-inhibitory role, highlighting its importance in modulating cellular processes such as proliferation, apoptosis, and immune responses. Additionally, TIMP-1 has garnered increasing attention as a prognostic biomarker and a potential therapeutic target in oncology. This review systematically compiles recent advancements in the understanding of TIMP-1's dual functions in cancer, elucidates its mechanistic roles as both a metalloproteinase inhibitor and a cytokine-like factor, and integrates its emerging significance as a biomarker and therapeutic target across diverse cancer types. By synthesizing recent findings, this study seeks to provide novel insights into the translational potential of TIMP-1 in cancer treatment, while examining its prospective implications for therapeutic strategies and clinical interventions.

Ferroptosis is a type of regulated cell death that depends on iron and lipid peroxidation and is considered a key pathological mechanism in a continuum of pathologies, including oncogenic, neurodegenerative, cardiovascular, and metabolic diseases. GPX4 serves as the regulator of ferroptosis, reducing the toxic lipid hydroperoxides to non-toxic lipid alcohols using the glutathione-dependent reaction and maintaining membrane integrity and cellular viability. MicroRNAs, short non-coding RNAs that regulate gene expression in a post-transcriptional manner, have been reported to play an important role in regulating both GPX4 expression and ferroptotic processes. This narrative review specifically focuses on microRNA-mediated regulation of GPX4, a central antioxidant regulator of ferroptosis, and explores the current evidence on miRNAs that modulate GPX4 expression across diverse disease contexts. This follows the miRNAs that directly target GPX4 through binding its 3'UTR, including hsa-miR-214-3p, hsa-miR-188-3p, hsa-miR-1909-5p, hsa-miR-761, hsa-miR-3619-5p, hsa-miR-15, and hsa-miR-324-3p, alongside miRNAs that indirectly modulate GPX4 via intermediate pathways such as Keap1/Nrf2, SLC7A11, and ACSL4. These microRNAs have demonstrated to have both pro-ferroptotic and anti-ferroptotic effects across a variety of disease models through in-silico predictions and experimental validation in each case, depending on the dynamics of their expression. Therapeutic interventions using microRNA-mimics, antagomirs, and adjunct therapeutic methods utilising natural compounds show the potential to control ferroptosis by regulating GPX4, thus providing new opportunities for the treatment of ferroptosis-related diseases.

Normal functioning of the brain consists of a complex set of physiological interactions occurring within specific anatomical sites of the brain. One of the most important areas within the brain responsible for a cohort of these homeostatic actions is the hippocampus. The hippocampus serves as a critical nexus for memory, emotion, and cognition. However, the widespread and often long-term use of psychotropic medications, particularly benzodiazepines, has raised concern regarding their potential structural and functional effects on this vulnerable region. Chronic benzodiazepine use remains common in psychiatric practice despite increasing concern regarding its long-term effects on hippocampal structure and cognitive health. As a neuroanatomical target of psychotropic medications, the hippocampus may be particularly susceptible to sustained pharmacologic modulation. Pharmaceutical drugs designed to modulate these hippocampal functions are not without potentially deleterious side effects. One such medication group, benzodiazepines, has been highlighted for its pleiotropic effects on hippocampal function. Evidence highlights that while chronic benzodiazepine use may diminish hippocampal volume, impair neuroplasticity, and heighten dementia risk, other medications such as lithium, gabapentin, and potential naturalistic treatments appear to counteract these effects by enhancing neurogenesis, synaptic resilience, and structural preservation. These GABAergic modulators, in combination with naturalistic modulators, further emphasize the potential for therapies that protect or even restore hippocampal integrity, offering promising alternatives to conventional treatments regarding chronic benzodiazepine use. Taken together, these findings reinforce the need for judicious prescribing practices and more research into neuroprotective strategies. The long-term structural health of the hippocampus carries direct implications for cognitive vitality and positive psychiatric outcomes. The use of lithium, in particular, may help mitigate benzodiazepine-associated adverse structural changes and potentially reduce the burden of neurodegenerative processes linked to hippocampal dysfunction. This review synthesizes current evidence regarding benzodiazepine-associated hippocampal changes and explores potential neuroprotective interventions that may mitigate structural vulnerability or support cognitive resilience.

Background: This study aimed to investigate the anticancer effects of lobaric acid (LA), a lichen acid, in MCF-7 cells. Our previous study demonstrated that LA exhibits anticancer effects by triggering apoptosis in MCF-7 cells. However, the relationship between this anticancer effect and the oxidative pathway and apoptosis mechanism has not been explained. In this study, the cytotoxic and anticancer effects of LA on MCF-7 cells were investigated through oxidative stress and thioredoxin system pathways.

Methods and results: For this purpose, reactive oxygen species (ROS), reduced glutathione (GSH), and malondialdehyde (MDA) levels were measured in MCF-7 cells exposed to LA at a concentration of 44.21 µg/mL (IC50). Additionally, the activities, gene, and protein levels of SOD, CAT, GPx, GST, GR, and TrxR enzymes were evaluated. In addition, the expression levels of TXN and TXNIP genes were also analyzed. The results showed that LA increased ROS and MDA levels and decreased GSH levels. Antioxidant enzyme activities (SOD, CAT, GR, TrxR) and protein levels decreased compared to the control, while heterogeneous changes were observed in gene expression levels. Despite increased GPX gene expression, a decrease in enzyme activity and protein levels was observed. While no change in TXN gene expression was observed, protein levels were decreased. TXNIP protein levels were also decreased.

Conclusions: The findings provide important data for evaluating lichen-derived compounds as potential anticancer agents targeting redox balance.