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Окисляющий стресс и воспаление в патогенезе неврологических расстройств: механизмы и последствия.

Нейрозащита — это активный подход к защите нервной системы, включая мозг, спинной мозг и периферийные нервы, путем предотвращения или ограничения повреждения нервных клеток и других компонентов. Она защищает центральную нервную систему от повреждений от острых и прогрессивных нейродегенеративных расстройств. Окисляющий стресс, дисбаланс между естественными механизмами защиты тела и образованием реактивных видов кислорода, имеет решающее значение для развития неврологических расстройств. Из-за высокой скорости метаболизма и потребления кислорода мозг особенно уязвим к окисляющему стрессу. Чрезм

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… One such process is cellular senescence, a state of irreversible growth arrest that can be induced by oxidative stress. As a consequence of cellular senescence, cells secrete various SASP factors. … Additionally, an increase in cellular senescence has been observed among these risk factors. …

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells.

: Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperaturesensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 °C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonprolifera

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… Cellular senescence in cancer and aging. Cell. 2007;130:223–233. doi: 10.1016/j.cell.2007.07.003. 41. Sherr C.J., Roberts J.M. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 2004;18:2699–2711. doi: 10.1101/gad.1256504. 42. … Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress. Nucleic Acids Res. 2015;43:6309–6320. doi: 10.1093/nar/gkv573. 43. Wang A.S., Ong P.F., Chojnowski A., Clavel C., Dreesen O. …

Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43

Идентификация и проверка генов, связанных со старением, у пациентов с множественной миеломой.

Это исследование было направлено на выявление и проверку связанных со старением генов (ARGs), связанных с множественной миеломой (MM), что способствовало более глубокому пониманию молекулярных механизмов, лежащих в основе этого заболевания. Для изучения функциональных ролей ARG в MM были проведены генной онтологии и Киото-Энциклопедии по обогащению генов и геномов. Потенциальные гены, выявленные с помощью наименьшего абсолютного сокращения и селекционного оператора (LASSO) логистической регрессии и рекурсивного устранения векторных функций (SVM-RFE), были сопоставлены с помощью диаграммы Венна

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… Activation of JUN has long been considered a hallmark of cellular senescence ( 28 ). The present study confirmed that TXN can serve as a promising diagnostic biomarker for MM, a malignant blood cancer characterized by uncontrolled plasma cell proliferation. … Senescence Trends Cell Biol 2018 28 436 453 2018 10.1016/j.tcb.2018.02.001 29477613 29 Matthews GM de Matos Simoes R Dhimolea E Sheffer M Gandolfi S Dashevsky O Sorrell JD Mitsiades CS NF-κB dysregulation in multiple myeloma Semin Cancer Biol 39 68 76 2016 10.1016/j.semcancer.2016.08.005 27544796 …

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream p

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… Recently, it was reported that Notch signaling ability to control the profile of cytokines secreted by tumor cells may be involved also in cancer cellular senescence. Cancer-associated cellular stress events, such as DNA damage or activation of oncogenes, may result in cellular senescence. … Cellular senescence is a process that leads cells to a permanent proliferative arrest during aging, embryogenesis, and cancer development. …

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

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… Tumour cells undergo irreversible cell cycle arrest due to replication stress‐induced DNA damage, telomere shortening, or exposure to chemotherapeutic drugs, leading to cellular senescence. … Excessive free radicals damage DNA, activate AMPK and upregulate p21, resulting in cell cycle arrest and the induction of cellular senescence. …

Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy.

BackgroundDegenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expressi

Priorities in Cardio-Oncology Basic and Translational Science: GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review.

Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to impro

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… Accordingly, genetic or pharmacologic PI3K-γ loss of function approaches resulted in increased mitophagy and protection against AIC. 13 Investigators from the consortium recently pinpointed a key function for the class II PI3K isoform, PI3K-C2α, in the control of cellular senescence by showing that loss … Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 2017;7:165–176. doi: 10.1158/2159-8290.CD-16-0241. 43. Mercurio V., Pirozzi F., Lazzarini E., et al. Models of heart failure based on the cardiotoxicity of anticancer drugs. …

Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations.

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to

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… Cellular senescence and inflammaging Cellular senescence and inflammaging cellular senescence and inflammaging are closely interconnected processes contributing to age-related diseases and declining tissue function 60 . … These factors can contribute to cellular senescence and inflammaging in the skin microenvironment. …

Does Regular Exercise Counter T Cell Immunosenescence Reducing the Risk of Developing Cancer and Promoting Successful Treatment of Malignancies?

Moderate intensity aerobic exercise training or regular physical activity is beneficial for immune function. For example, some evidence shows that individuals with an active lifestyle exhibit stronger immune responses to vaccination compared to those who are inactive. Encouragingly, poor vaccine responses, which are characteristic of an ageing immune system, can be improved by single or repeated bouts of exercise. In addition, exercise-induced lymphocytosis, and the subsequent lymphocytopenia, is thought to facilitate immune surveillance, whereby lymphocytes search tissues for antigens derived

Drugging the efferocytosis process: concepts and opportunities.

The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infe

Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.

Second primary cancers (SPCs) pose an increasingly significant clinical challenge for survivors of hematologic malignancies, attributed to improved therapeutic outcomes and prolonged survival. The development of SPCs is influenced by a complex interplay of treatment-related factors, genetic susceptibility, immune dysregulation, and microenvironmental remodeling. This narrative review summarizes the epidemiological patterns of SPCs in survivors of hematologic malignancies and discusses the underlying biological mechanisms, including therapy-induced genomic instability, clonal hematopoiesis, inf

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… Based on current evidence, the principal contributors to SPCs risk can be categorized into four domains: cellular senescence associated with aging, metabolic dysregulation, oncogenic viral infections, and immune dysfunction accompanied by chronic inflammation ( Figure 1 ). … Off-target radiation and cytotoxic agents cause DNA single-strand breaks and cellular senescence, while concurrently activating cancer-associated fibroblasts (CAFs) that remodel the bone marrow niche through proinflammatory cytokine secretion and metabolic reprogramming. …

Updates in Anthracycline-Mediated Cardiotoxicity.

Cardiotoxicity is one of the main adverse effects of chemotheraphy, affecting the completion of cancer therapies and the short- and long-term quality of life. Anthracyclines are currently used to treat many cancers, including the various forms of leukemia, lymphoma, melanoma, uterine, breast, and gastric cancers. World Health Organization registered anthracyclines in the list of essential medicines. However, anthracyclines display a major cardiotoxicity that can ultimately culminate in congestive heart failure. Taking into account the growing rate of cancer survivorship, the clinical significa

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… Cardiac Fibroblasts Doxorubicin treatment promotes cellular senescence and induces the differentiation of cardiac fibroblasts to a pro-fibrotic phenotype, myofibroblasts ( Cappetta et al., 2016 ). …

Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.

Multiple myeloma (MM) is a hematological malignancy defined by the abnormal proliferation and accumulation of plasma cells (PC) within the bone marrow (BM). While multiple myeloma impacts the bone, it is not classified as a primary bone cancer. The bone marrow microenvironment significantly influences the progression of myeloma and its treatment response. Mesenchymal stromal cells (MSCs) in this environment engage with myeloma cells and other bone marrow components via direct contact and the secretion of soluble factors. This review examines the established roles of MSCs in multiple facets of

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… In contrast, severe hypoxia (< 1% O₂) triggers oxidative stress, resulting in cellular senescence and diminished regenerative capacity. …

Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.

Cardio-oncology is an emerging field that seeks to enhance quality of life and longevity of cancer survivors. It is pertinent for clinicians to understand the cellular mechanisms of prescribed therapies, as this contributes to robust understanding of complex treatments and off-target effects, improved communication with patients, and guides long term care with the goal to minimise or prevent cardiovascular complications. Our aim is to review the cellular mechanisms of cardiotoxicity involved in commonly used anti-cancer treatments and identify gaps in literature and strategies to mitigate card

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… The link between increased ROS and onset of cellular senescence is firmly established ( 33 , 34 ). Senescence is characterized as a cellular stress response that can elicit cell reactions resulting in temporary adaptations to stressors, induce autophagy, or activate cell death ( 35 ). … Cellular senescence and oxidative and stress remain possible targets for treatment of ACT and are an active area of research with specific targets still under investigation. …

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

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… Senescence The irreversible cell cycle arrest will lead to cellular senescence that can limit the expansion of mutations in cells [ 38 ]. Therefore, senescence is a way to prevent cancer. … Resveratrol metabolites can promote a moderate cellular senescence induction in breast cancer cells, which involves inhibiting cell growth by G 2 /M phase arrest through the p53/p21Cip1/WAF1 pathway [ 180 ]. …

Longevity leap: mind the healthspan gap.

Life expectancy has increased by three decades since the mid-twentieth century. Parallel healthspan expansion has however not followed, largely impeded by the pandemic of chronic diseases afflicting a growing older population. The lag in quality of life is a recognized challenge that calls for prioritization of disease-free longevity. Contemporary communal, clinical and research trends aspiring to extend the health horizon are here outlined in the context of an evolving epidemiology. A shared action integrating public and societal endeavors with emerging interventions that target age-related m

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… The research dimension Targeting senescent cells Cellular senescence and stem cell exhaustion, in conjunction with prime pathological states, such as genomic instability, telomere attrition, and mitochondrial dysfunciton, are hallmarks of aging 58 . … New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 2021;106:e1481–e1487. doi: 10.1210/clinem/dgaa728. 65. Hickson LJ, et al. …

Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

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… In the postmenopausal/aged PMOP state, MSCs exhibit elevated ROS, DNA damage, and cellular senescence, along with downregulation of CXCR4, EBF1, and SLC6A6 expression, impaired BMP signaling, and disrupted oxidative phosphorylation. …

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy.

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and

The integration of machine learning and multi-omics analysis provides a powerful approach to screen aging-related genes and predict prognosis and immunotherapy efficacy in hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is a highly malignant tumor with high incidence and mortality rates. Aging-related genes are closely related to the occurrence and development of cancer. Therefore, it is of great significance to evaluate the prognosis of HCC patients by constructing a model based on aging-related genes.MethodNon-negative matrix factorization (NMF) clustering analysis was used to cluster the samples. The correlation between the risk score and immune cells, immune checkpoints, and Mismatch Repair (MMR) was evaluated through Spearman correlation test. Real Time Quantitati

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… And the main pathways enriched by KEGG analysis are cell cycle, cellular senescence, central carbon metabolism in cancer, and HIF-1 signaling pathway ( Figure 2E ). Figure 1 A flow chart of the manuscript. … Interesting KEGG pathway enrichment included Cell cycle, Cellular senescence, and HIF-1 signaling pathway. …