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Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.

BackgroundMultiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance.MethodsThis study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO.Resu

Nrf2-Независимое антивоспалительное воздействие диметилфумарата: проблемы и перспективы развития электрофильных Nrf2 активаторов нейродегенеративных заболеваний.

Связанный с NF-E2 путь 2 (Nrf2)-антиоксидантный элемент реакции (ARE) является потенциальной терапевтической целью для заболеваний центральной нервной системы. В настоящем обзоре подчеркивается роль окислительного стресса и нейронного воспаления в нейродегенеративных заболеваниях с уделением особого внимания терапевтическому потенциалу таких активаторов Nrf2, как диметилфумарат (ДМФ). ДМФ, первоначально применяемый для лечения псориаза, продемонстрировал эффективность при множественном склерозе и метаболизируется до монометила фумарата, что может оказывать значительное терапевтическое воздейст

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… The oxidation state of these cysteine residues can affect the activity of ATG4, thereby regulating the cleavage and lipidation of LC3/ATG8, critical steps in autophagosome formation and maturation [ 147 ]. … First, these damaged proteins are marked for degradation through ubiquitination, allowing them to be recognized and transferred into autophagosomes for degradation, thereby maintaining intracellular homeostasis. …

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

Physiological functions and pharmacological targeting of transient receptor potential channels.

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 he

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

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… METTL3 and YTHDF1 enhance Rubicon mRNA stability, inhibiting autophagosome–lysosome fusion and lipid droplet clearance. (C) RNA modifications in ferroptosis. FTO demethylates OTUB1 mRNA, inhibiting ferroptosis and enhancing radioresistance. FTO downregulates SLC7A11, promoting ferroptosis. … Rubicon, in turn, inhibits the fusion process between autophagosomes and lysosomes, obstructing the clearance of LDs. 238 Ferroptosis is an emerging form of programmed cell death characterized by the accumulation of intracellular iron and subsequent peroxidation of lipids 239 (Figure 4C ). …

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

Использование естественных экзоцитозных везикул для борьбы с возрастными заболеваниями: от возрастных драйверов до терапевтических возможностей.

Старение — это сложный биологический процесс, приводящий к увеличению нагрузки возрастных заболеваний (ARD). Клеточная старость, включающая необратимое остановку клеточного цикла и выделение фенотипа секреторной активности при старении (SASP), играет центральную роль в старении и развитии ARD. Естественные экзоцитические везикулы (NEVs) — это везикулы, полученные из клеток, органов и тканей без искусственных вмешательств. В последние годы NEVs привлекли внимание как медиаторы межклеточной коммуникации, и показали многофункциональный потенциал в регулировании клеточной старости и ARD. С одной с

Exploring the Molecular Mechanisms by Which DEHP Promotes the Occurrence and Progression of Kidney Stones Based on Network Toxicology and Experimental Validation.

BACKGROUND: The global burden of kidney stones is increasing, while di(2-ethylhexyl) phthalate (DEHP), a widespread plasticizer and endocrine-disrupting pollutant, has been implicated as a potential environmental risk factor. This study investigated the mechanisms by which DEHP may aggravate calcium oxalate kidney stones through network toxicology, computational analyses, and experimental validation. METHODS: DEHP- and kidney stone-related targets were retrieved from six databases. Shared targets were analyzed using protein-protein interaction networks and Gene Ontology and Kyoto Encyclopedia

Matrine in cancer therapy: antitumor mechanisms and nano-delivery strategies.

Cancer remains one of the leading causes of death worldwide. The severe adverse reactions and toxic side effects associated with conventional treatments such as surgery, radiotherapy, and chemotherapy pose significant challenges for researchers and clinical practitioners. These limitations have driven the pursuit of more advanced and effective therapeutic approaches. In recent years, natural products have attracted considerable attention in the field of disease treatment and have become an important source for new drug development. Matrine, a major active component of the traditional medicinal

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… Arrows indicate promotion and inhibition pathways. 3.3 Induction of autophagy in tumor cells Autophagy is an evolutionarily conserved stress response and degradation mechanism involving the delivery of damaged or dysfunctional intracellular components to lysosomes via double-membrane autophagosomes …

Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types

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… Another essential protein known as p62 or sequestosome 1 (SQSTM1) directly attaches to LC3-II through a particular sequence motif to produce autophagosomes, which then go through self-degradation during autophagy. …

Fucoidan: An Update on Function, Role in Human Health and Applications.

Fucoidan is a polysaccharide bioactive compound, mainly from brown algae, characterized by multiple biological activities, including anti-inflammatory, anticoagulant, anticancer, antioxidant, antiviral, and cardioprotective properties. In addition, growing scientific evidence supports its epigenetic potential and ability to modulate autophagic mechanisms, two crucial aspects for the treatment and prevention of chronic diseases, such as cancer, inflammation, and aging. For this reason, Fucoidan is a promising candidate for a wide range of applications, both as a bioactive component of drug deli

Adoptive immune cell therapy for colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the

Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers

Anticancer peptides as novel immunomodulatory therapeutic candidates for cancer treatment.

Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further n

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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… Common mechanisms for protein stabilization encompass: (1) The role of ribosomes enhances the accurate translation of RNA into proteins, ensuring protein stability [ 30 ]. (2) Lysosomes selectively degrade proteins containing the KEFRQ motif through chaperone-mediated autophagy (CMA) [ 31 ]. (3) The autophagosomes …

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that t

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… GABARAP has been reported to be an important contributor to the autophagosomes mediating autophagy, the process by which lysosomes degrade and recycle damaged organelles as a means for cells to control proliferation and the formation of radical inorganic species ( Liu et al., 2016 ). …

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment.

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs' safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in

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… . | Blockage of autophagy by inhibiting the fusion of autophagosomes with lysosomes. | [ 74 ] Desmethylclomipramine | Inhibits in vitro the E3 ubiquitin ligase Itch. | Inhibits lung cancer stem cells’ growth, decreases their stemness potential, and increases the cytotoxic effect of conventional chemotherapeutic …