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Структурно-ориентированное понимание специфичности 2ДГ-III реберосчег.

Рибосчемы сохраняют некодированные домена РНК, в основном расположенные на 5'-конец бактериальных MRNA, которые служат регулятором генного экспрессии. Недавно третий класс 2Дексигуанозин реберосколка.2'-dG-III) был идентифицирован из семейства рибоколдов, проявляющих сопоставимую связь с 2ДиДжи, Гунанин и гуанозин. Чтобы прояснить уникальный механизм распознавания лиганда, мы раскрыли его кристаллы в комплексе с различными производными пурины, включая 2ДиДжи, Гунанин и гуанозин. Трехсторонняя структура показывает типичную архитектуру, похожую на вилку, с three вырезки, соединяющиеся в центре t

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… Well-diffracted crystals of 2′-dG-III riboswitch bound to 2′-dG grew within 2 days under conditions containing 0.08 M Sodium chloride, 0.012 M Potassium chloride, 0.02 M Magnesium chloride hexahydrate, 0.04 M Sodium cacodylate trihydrate, pH 7.0, 30%–35% v/v (±)-2-Methyl-2,4-pentanediol, and 0.012 M Spermine …

The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility.

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular gro

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… Antitumor agent PX-12 inhibits HIF-1α protein levels through an Nrf2/PMF-1-mediated increase in spermidine/spermine acetyl transferase. Cancer Chemother. Pharmacol. 2011;68:405–413. doi: 10.1007/s00280-010-1500-0. 64. …

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

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… (Sage) | Solvent diffusion technique | FPSP/EO/silver nanoparticles, PSP/silver/EO | PLA-Spermine-PEG-FA (FPSP) copolymer nanoparticles | β-thujone, α-thujone, camphor, 1,8-cineole | Size: 200–300 nm (FPSP/silver/EO ~249 nm); Zeta: -20.6 ± 1.3 mV (FPSP/silver/EO), -18.3 ± 0.7 mV (PSP/silver/EO); Spherical …

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the po

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… Spermine as an autophagy inducer, inhibits autophagy EP300, an endogenous inhibitory factor to delay the progression of some age-related diseases [ 42 ]. …

Микробиота человека в области здравоохранения и отдельные раковые заболевания.

Большинство эпителиальных поверхностей нашего тела, пищеварительный тракт, дыхательные и врожденные системы, колонизируются большим количеством бактерий, археи, грибов, протозоанов и вирусов. Эти микробиота, особенно кишки, играют важную и полезную роль в пищеварении, метаболизме и синтезе витаминов. Их метаболиты стимулируют производство цитокина человеком, которое используется против потенциальных патогенов. На состав микробиоты влияет ряд внутренних и внешних факторов, включая питание, возраст, болезни и образ жизни. Такие изменения, называемые дисбиозом, могут быть связаны с развитием разл

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… The B. fragilis -derived toxin (BFT) produced by these bacteria activates spermine oxidase produced by the host; its activation generates hydrogen peroxide and reactive oxygen species that damage the DNA in epithelial cells, promoting tumorigenesis [ 256 ]. …

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries.

Prostate cancer is the most common cancer in men, with over 52,000 new cases diagnosed every year. Diagnostics and early treatment are potentially hindered by variations in screening protocols, still largely reliant on serum levels of acid phosphatase and prostate-specific antigen, with tumour diagnosis and grading relying on histopathological examination. Current treatment interventions vary in terms of efficacy, cost and severity of side effects, and relapse can be aggressive and resistant to the current standard of care. For these reasons, the scientific community is looking for new chemoth

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… In 2001, a class of alkaloid compounds containing a spermine-like substructure, named motuporamine, were isolated from the marine sponge Xestospongia exigua. These compounds were shown to play a role in the inhibition of invasion of basement membrane gels by PC3 cells [ 71 ]. …

Unlocking the Microbial Symphony: The Interplay of Human Microbiota in Cancer Immunotherapy Response.

IntroductionThe emergence of cancer immunotherapy has revolutionized cancer treatment, offering remarkable outcomes for patients across various malignancies. However, the heterogeneous response to immunotherapy underscores the necessity of understanding additional factors influencing treatment efficacy. Among these factors, the human microbiota has garnered significant attention for its potential role in modulating immune response. Body: This review explores the intricate relationship between the human microbiota and cancer immunotherapy, highlighting recent advances and potential mechanisms u

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… Spermine oxidase mediates Helicobacter pylori-induced gastric inflammation, DNA damage, and carcinogenic signaling. Oncogene. 2020;39:4465–4474. doi: 10.1038/s41388-020-1304-6. 71. Wu M., Tian C., Zou Z., Jin M., Liu H. …

Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.

Alternative splicing (AS) is the central mechanism of transcriptional regulation and generates diverse splice variants that influence protein structure, function, and intracellular activity. AS plays critical roles in tissue differentiation, organ development, and disease progression. This review focuses on the pivotal roles of AS in bone biology, highlighting its regulatory effects on osteoblasts, osteoclasts, chondrocytes, bone matrix remodeling, and bone remodeling, as well as the involvement of AS-related RNA-binding proteins in these processes. We also emphasize bone-specific AS events an

Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

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… By comparing the SAR with the structurally similar guanidine-based alkaloid Ptilomycalin A, it was found that they had a high Pearson correlation (0.638), indicating that the pentacyclic guanidine core skeleton and the spermine fragment at the end are crucial for its anti-tumor activity. …

MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.

Homozygous deletion of the 9p21.3 genomic locus spanning the CDKN2A/B and MTAP genes is an event affecting 15% of cancers. While CDKN2A is a well-established tumor suppressor gene, the role of MTAP in tumorigenesis varies across cancer types. MTAP codes for methylthioadenosine phosphorylase, a key enzyme in the methionine salvage pathway, and its loss has been associated with several downstream synthetic vulnerabilities. Despite multiple efforts to exploit MTAP loss for targeted therapies, none of these efforts have yielded substantial results in clinical trials. In this review, we consolidate

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… Furthermore, MTAP loss triggers activation of ornithine decarboxylase (ODC), the enzyme that catalyzes the conversion of ornithine to putrescine and subsequently spermidine and spermine [ 60 ]. …

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

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… Thiazole orange - Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19 . Eur J Med Chem . 2019 ; 175 : 20 – 33 . 31071547 10.1016/j.ejmech.2019.04.041 42. Biffi G , Tannahill D , Miller J , Howat WJ , Balasubramanian S . …

A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.

Molecular glue degraders (MGDs) constitute a class of innovative therapeutic agents within the field of targeted protein degradation (TPD). In contrast to proteolysis-targeting chimeras (PROTACs), MGDs induce protein degradation by stabilizing the interaction between an E3 ubiquitin ligase and a target protein. They typically exhibit favorable drug-like characteristics, including lower molecular weight and enhanced bioavailability. Although their discovery was historically serendipitous, recent advances in high-throughput screening, bioinformatics, and artificial intelligence are enabling more

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod

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… More advanced platforms incorporating calcium carbonate nanoparticles, folic acid, and supramolecular peptides undergo intracellular self-assembly in spermine-rich tumor cells, forming micrometer-scale aggregates that prolong retention, induce calcium overload, disrupt mitochondrial integrity, and trigger …

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

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… Mechanistically, acetate induces lysine acetylation modification of sp1 transcription factor (SP1) via acyl‐CoA synthetase short chain family member 2 (ACSS2), enhancing its stability and subsequently triggering spermidine/spermine N1‐acetyltransferase 1 (SAT1)‐dependent polyamine metabolism [ 88 ]. …

P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome.

P-glycoprotein (P-gp), a transmembrane efflux pump encoded by the ABCB1/MDR1 gene, is a major contributor to multidrug resistance in hematological malignancies. These malignancies, arising from hematopoietic precursors at various differentiation stages, can manifest in the bone marrow, circulate in the bloodstream, or infiltrate tissues. P-gp overexpression in malignant cells reduces the efficacy of chemotherapeutic agents by actively expelling them, decreasing intracellular drug concentrations, and promoting multidrug resistance, a significant obstacle to successful treatment. This review exa

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues.

Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still t

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… Levels of metabolites associated with prostate function, including citrate, aspartic acid, zinc, and spermine were higher in noncancer epithelium than in tumor. …

m5C RNA methylation in cancer: from biological mechanism to clinical perspectives.

Cancer remains a significant global health threat, characterized by high morbidity and mortality rates. Despite advancements, numerous challenges persist in cancer treatment, underscoring the urgent need for novel therapeutic strategies. As a burgeoning area of cancer research, increasing evidence highlights the critical role of 5-methylcytosine (m5C) methylation in tumorigenesis, progression, and clinical application. In this review, we systematically review the biological mechanism and clinical translational potential of m5C RNA methylation in cancer and analyze in detail the dynamic interac

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… Additionally, YBX1, promotes the progression of esophageal squamous cell carcinoma (ESCC) by stabilizing spermine oxidase (SMOX) mRNA to activate mTORC1 pathway [ 87 ]. …

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… Putrescine is the precursor of polyamines such as spermidine and spermine, which are cationic proteins that control cell functions such as growth, proliferation, differentiation, motility and survival via their interactions with negatively charged macromolecules such as nucleic acids or proteins. …

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discuss

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… Sustained decrease of THF-mediated methylation downregulates an accumulation of spermine and spermidine polyamines in the extracellular fluids and lymphocytes of patients with RA [ 58 , 59 ]. These polyamines are essential cellular growth factors among others in lymphocytes. …