Design of a Magnetic Nanoplatform Based on CD26 Targeting and HSP90 Inhibition for Apoptosis and Ferroptosis-Mediated Elimination of Senescent Cells.

The accumulation of senescent cells, a hallmark of aging and age-related diseases, is also considered as a side effect of anticancer therapies, promoting drug resistance and leading to treatment failure. The use of senolytics, selective inducers of cell death in senescent cells, is a promising pharmacological antiaging and anticancer approach. However, more studies are needed to overcome the limitations of first-generation senolytics by the design of targeted senolytics and nanosenolytics and the validation of their usefulness in biological systems.

New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells.

Mitochondria are considered as promising targets for cancer treatment. In the present study, triphenyl phosphonium cationic group-conjugated fisetin (mito-fisetin) was synthesized, and its anticancer activity was investigated in several cellular models of estrogen receptor (ER)-positive breast cancer in vitro and in vivo in proliferating and tamoxifen-promoted senescent states. Mito-fisetin, when used at low micromolar concentrations, stimulated the dissipation of mitochondrial membrane potential and oxidative stress, and affected mitochondrial function, resulting in apoptosis induction in senescent breast cancer cells.

Anticancer Activity of Encapsulated Pearl Millet Polyphenol-Rich Extract against Proliferating and Non-Proliferating Breast Cancer Cells In Vitro.

Plant-derived polyphenols are bioactive compounds with potential health-promoting properties including antioxidant, anti-inflammatory, and anticancer activity. However, their beneficial effects and biomedical applications may be limited due to their low bioavailability. In the present study, we have considered a microencapsulation-based drug delivery system to investigate the anticancer effects of polyphenol-rich (apigenin, caffeic acid, and luteolin) fractions, extracted from a cereal crop pearl millet (), using three phenotypically different cellular models of breast cancer in vitro, namely triple negative HCC1806, ER-positive HCC1428, and HER2-positive AU565 cells.

Carbon-Coated Iron Oxide Nanoparticles Promote Reductive Stress-Mediated Cytotoxic Autophagy in Drug-Induced Senescent Breast Cancer Cells.

The surface modification of magnetite nanoparticles (FeO NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of FeO NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, FeO NPs coated by dextran (FeO@Dex) and glucosamine-based amorphous carbon coating (FeO@aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells).

Mutation Status and Glucose Availability Affect the Response to Mitochondria-Targeted Quercetin Derivative in Breast Cancer Cells.

Mitochondria, the main cellular power stations, are important modulators of redox-sensitive signaling pathways that may determine cell survival and cell death decisions. As mitochondrial function is essential for tumorigenesis and cancer progression, mitochondrial targeting has been proposed as an attractive anticancer strategy. In the present study, three mitochondria-targeted quercetin derivatives (mitQ3, 5, and 7) were synthesized and tested against six breast cancer cell lines with different mutation and receptor status, namely ER-positive MCF-7, HER2-positive SK-BR-3, and four triple-negative (TNBC) cells, i.

TRDMT1-mediated RNA C-5 methylation as a novel target in anticancer therapy.

Affected landscape of RNA modifications is frequently observed in different cancer cells that can be associated with the development of cancer cell phenotypic traits such as sustained proliferation, migration and invasion, apoptosis resistance and metabolic reprograming. DNMT2/TRDMT1 5-methylcytosine methyltransferase, initially classified as DNA methyltransferase, can methylate both tRNA and mRNA promoting tRNA stability and proper protein synthesis, and orchestrating DNA damage response (DDR) and DNA stability, respectively. TRDMT1 is associated with cancer progression as its levels can be elevated and its mutations can be observed in a number of cancer types.

Electrospun fiber-based micro- and nano-system for delivery of high concentrated quercetin to cancer cells.

The anticancer potential of quercetin (Q), a plant-derived flavonoid, and underlining molecular mechanisms are widely documented in cellular models in vitro. However, biomedical applications of Q are limited due to its low bioavailability and hydrophilicity. In the present study, the electrospinning approach was used to obtain polylactide (PLA) and PLA and polyethylene oxide (PEO)-based micro- and nanofibers containing Q, namely PLA/Q and PLA/PEO/Q, respectively, in a form of non-woven fabrics.

Knockout of TRDMT1 methyltransferase affects DNA methylome in glioblastoma cells.

Purpose: We have previously shown that TRDMT1 methyltransferase is a regulator of chemotherapy-associated responses in glioblastoma cells. Despite the fact that glioblastoma, a common and malignant brain tumor, is widely characterized in terms of genetic and epigenetic markers, there are no data on TRDMT1-related changes in 5-methylcytosine pools in the genome. In the present study, the effect of TRDMT1 gene knockout (KO) on DNA methylome was analyzed.

Telomere loss is accompanied by decreased pool of shelterin proteins TRF2 and RAP1, elevated levels of TERRA and enhanced glycolysis in imatinib-resistant CML cells.

Telomere length may be maintained by telomerase nucleoprotein complex and shelterin complex, namely TRF1, TRF2, TIN2, TPP1, POT1 and RAP1 proteins and modulated by TERRA expression. Telomere loss is observed during progression of chronic myeloid leukemia (CML) from the chronic phase (CML-CP) to the blastic phase (CML-BP). The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), has changed outcome for majority of patients, however, a number of patients treated with TKIs may develop drug resistance.

Non-targeting siRNA-mediated responses are associated with apoptosis in chemotherapy-induced senescent skin cancer cells.

It is widely accepted that siRNA transfection can promote some off-target effects in the genome; however, little is known about how the cells can respond to the presence of non-viral dsRNA. In the present study, non-targeting control siRNA (NTC-siRNA) was used to evaluate its effects on the activity of pathogen and host-derived nucleic acid-associated signaling pathways such as cGAS-STING, RIG-I, MDA5 and NF-κB in A431 skin cancer cells and BJ fibroblasts. NTC-siRNA treatment promoted cytotoxicity in cancer cells.

DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis.

The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may exert an important cytoprotective role by promoting folding of newly synthesized proteins and cancer cell survival. The lack of DNMT2/TRDMT1 methyltransferase-mediated C38 tRNA methylation compromises translational fidelity that may result in the accumulation of misfolded and aggregated proteins leading to proteotoxic stress-related cell death. In the present study, DNMT2/TRDMT1 gene knockout-mediated effects were investigated during doxorubicin (DOX)-induced ER stress and PERK-, IRE1- and ATF6-orchestrated UPR in four genetically different cellular models of cancer (breast and cervical cancer, osteosarcoma and glioblastoma cells).

Synergic Temperature Effect of Star-like Monodisperse Iron Oxide Nanoparticles and Their Related Responses in Normal and Cancer Cells.

Magnetic nanoparticle (MNP) anisotropy has been tailored by the preparation of MNPs having different shapes (star-like, cubic, and polyhedral) using a self-modified rapid hot-injection process. The surface modification of MNPs was performed through etidronic ligand grafting with a strong binding affinity to mixed metal oxides, ensuring sufficient colloidal stability, surface protection, and minimized aggregation and interparticle interactions. The heating effect was induced by contactless external stimulation through the action of an alternating magnetic field and NIR laser radiation (808 nm).

RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines.

Osteosarcoma (OS) is a pediatric malignant bone tumor with unsatisfying improvements in survival rates due to limited understanding of OS biology and potentially druggable targets. The present study aims to better characterize osteosarcoma U-2 OS, SaOS-2, and MG-63 cell lines that are commonly used as models of OS. We focused on evaluating the differences in cell death pathways, redox equilibrium, the activity of proliferation-related signaling pathways, DNA damage response, telomere maintenance, DNMT2/TRDMT1-based responses and RNA 5-methylcytosine status.

Lapatinib- and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status.

Lapatinib (L) and fulvestrant (F) are used in targeted anticancer therapies, in particular, against phenotypically different breast cancer cells. L, a dual inhibitor of EGFR and HER2 tyrosine kinases, is active against HER2-positive breast cancer cells, while F, a selective estrogen receptor degrader (SERD), is active against ER-positive breast cancer cells. However, the action of L and F can be limited due to their relatively low water solubility and bioavailability.

Optical Control of Tissue Regeneration through Photostimulation of Organic Semiconducting Nanoparticles.

Next generation bioengineering strives to identify crucial cues that trigger regeneration of damaged tissues, and to control the cells that execute these programs with biomaterials and devices. Molecular and biophysical mechanisms driving embryogenesis may inspire novel tools to reactivate developmental programs in situ. Here nanoparticles based on conjugated polymers are employed for optical control of regenerating tissues by using an animal with unlimited regenerative potential, the polyp Hydra, as in vivo model, and human keratinocytes as an in vitro model to investigate skin repair.

5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells.

5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options.

Evaluation of Anticancer and Antibacterial Activity of Four 4-Thiazolidinone-Based Derivatives.

Heterocycles are commonly known for their unique features, e.g., antibacterial or anticancer properties.

Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups.

Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such as senescence-associated secretory phenotype (SASP), secondary senescence, and cancer promotion. Targeted elimination of senescent cells can be achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated with kinase inhibitor dasatinib. In the present study, three quercetin derivatives were synthesized and tested for improved senolytic action against etoposide-induced senescent human normal mammary epithelial cells and triple-negative breast cancer cells in vitro.

Deficiency of TRDMT1 impairs exogenous RNA-based response and promotes retrotransposon activity during long-term culture of osteosarcoma cells.

TRDMT1 methyltransferase is postulated to be a novel target in anticancer therapy as TRDMT1-mediated RNA methylation is involved in DNA damage response (DDR) and TRDMT1 deficient cells are sensitive to PARP1 inhibitors. However, the effects of TRDMT1 gene knockout (KO) during cancer cell selection upon drug stimulation and the involvement of exogenous RNA were not addressed. In the present study, osteosarcoma (OS) cells lacking active TRDMT1 gene were subjected to short-term treatment of etoposide in the presence of exogenous RNA and long-term effects were analyzed after drug removal.

Silver birch pollen-derived microRNAs promote NF-κB-mediated inflammation in human lung cells.

The pollen of Betula pendula Roth (silver birch) is considered to be the main cause of allergy-related rhinitis in Europe and its protein-based allergens such as Bet v 1 are well characterized. However, little is known about non-protein components of birch pollen, e.g.

Multimodal polymer encapsulated CdSe/FeO nanoplatform with improved biocompatibility for two-photon and temperature stimulated bioapplications.

Multimodal polymer encapsulated CdSe/FeO nanoplatforms with dual optical and magnetic properties have been fabricated. We demonstrate that CdSe/FeO nanocapsules (NCs) upon excitation with UV radiation or NIR fs-laser excitation exhibit intense one- or two-photon emission at 535 nm, whereas the combination of an alternating magnetic field and 808 nm IR laser excitation results in heat generation. Since anticancer therapies require relatively high doses of FeO nanoparticles (NPs) to induce biologically relevant temperature jumps, the therapeutic effects of 0.

The lack of functional gene modulates cancer cell responses during drug-induced senescence.

Cellular senescence may be a side effect of chemotherapy and other anti-cancer treatments that may promote inflammation and paracrine secondary senescence in healthy tissues. DNMT2/TRDMT1 methyltransferase is implicated in the regulation of cellular lifespan and DNA damage response (DDR). In the present study, the responses to senescence inducing concentrations of doxorubicin and etoposide in different cancer cells with gene knockout were evaluated, namely changes in the cell cycle, apoptosis, autophagy, interleukin levels, genetic stability and DDR, and 5-mC and NSUN1-6 levels.

The Identification of a Novel Fucosidosis-Associated Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns.

Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. mutations lead to severe reduction or even loss of α-L-fucosidase enzyme activity.