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Label-Free Impedance-Based Real-Time Cell Analysis Platform: An Advanced Technology Designed to Monitor the Cytotoxic Activity of Natural Killer Cells.

Natural killer (NK) cells play a key role in targeting cancer, virus-infected, and senescent cells through direct cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC). Monitoring NK cell cytotoxicity is crucial for evaluating immune function, tracking disease progression, and assessing therapeutic outcomes, particularly in oncology and immunology. NK cells help manage infections, cancer, and other health conditions through their cytotoxic actions. Changes in NK activity can signal disease states or responses to treatments. NK cell-based therapies require functional assessments to m

Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family.

Cells survive and reproduce by coping with acute or chronic exposure to a fixed elevated temperature or fluctuating temperatures. These properties are one of the main evolutionary forces and involve the heat shock response. This response is characterized by the induction of heat-shock proteins (HSPs) and is mainly regulated by heat-shock transcription factors (HSFs) in vertebrates. A single HSF is present in yeast and invertebrates, such as Caenorhabditis elegans and Drosophila, whereas vertebrates have evolved multiple HSFs. The potential of HSFs to induce HSP expression is linked to the amin

Beyond the hype: the glycolysis-pyroptosis axis in intervertebral disc degeneration and the path to therapeutic translation.

The recent study by Gao et al. (Apoptosis, 2025. https://doi.org/10.1007/s10495-025-02194-x ) proposes a compelling paradigm in which a positive feedback loop between glycolysis and nucleus pulposus cell pyroptosis acts as a central driver of intervertebral disc degeneration. Their work provides a crucial mechanistic link between dysregulated metabolism and inflammatory cell death, building upon long-standing observations of lactic acid accumulation and cellular demise in the degenerative disc. While this refined model represents a significant conceptual advance, our commentary identifies seve

Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging.

The increasing global prevalence of diabetic nephropathy poses substantial health and economic burdens. Currently, effective anti-fibrotic t … umulation and pathological impact. The pathogenic mechanism of corisin involves the acceleration of cellular senescence and the induction of epithelial-mesenchymal transition and apoptosis in kidney cells. These findings underscore the critical role of corisin in progressive diabetic nephropathy and suggest a promising new target for therapeutic intervention.

Arsenic and metabolic diseases: New insights from mesenchymal stem cells.

Arsenic is a common toxic metal contaminant in the environment. Humans are exposed to arsenic through drinking water, air, food, and medical … y of MSCs, leads to changes in the synthesis and secretion of immunomodulatory factors, and induces cellular senescence and apoptosis. Therefore, dysfunction and death of MSCs may be important pathogenesis of arsenic-related metabolic diseases. Future studies on the functional changes of MSCs in arsenic-related metabolic diseases and the role of MSCs in arsenic patho …

Irisin in degenerative musculoskeletal diseases: Functions in system and potential in therapy.

Degenerative musculoskeletal diseases are a class of diseases related to the gradual structural and functional deterioration of muscles, joints, and bones, including osteoarthritis (OA), osteoporosis (OP), sarcopenia (SP), and intervertebral disc degeneration (IDD). As the proportion of aging people around the world increases, degenerative musculoskeletal diseases not only have a multifaceted impact on patients, but also impose a huge burden on the medical industry in various countries. Therefore, it is crucial to find key regulatory factors and potential therapeutic targets. Recent studies ha

Polypyridiniums with Inherent Autophagy-Inducing Activity for Atherosclerosis Treatment by Intracellularly Co-Delivering Two Antioxidant Enzymes.

Atherosclerosis is a chronic inflammatory disease of the arterial intima and is becoming the leading cause of morbidity and mortality worldwide. There is considerable evidence that defective autophagy and overproduction of reactive oxygen species (ROS) are closely involved in the development and progression of atherosclerosis. Here, a polymer is developed with the inherent autophagy-inducing activity to treat atherosclerosis by co-delivering antioxidant enzymes. The lead material P5c screened from a library of polypyridiniums shows robust efficacy in cytosolic protein delivery, and efficiently

Telomerase-targeted therapies in myeloid malignancies.

Human telomeres are tandem arrays that are predominantly composed of 5'-TTAGGG-3' nucleotide sequences at the terminal ends of chromosomes. These sequences serve 2 primary functions: they preserve genomic integrity by protecting the ends of chromosomes, preventing inappropriate degradation by DNA repair mechanisms, and they prevent loss of genetic information during cellular division. When telomeres shorten to reach a critical length, termed the Hayflick limit, cell senescence or death is triggered. Telomerase is a key enzyme involved in synthesizing and maintaining the length of telomeres wit

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… Nonfunctional hTERT causes the shortening of TL with each division and subsequent cellular senescence or apoptosis in both solid tumor and hematologic malignancy cell types. 49 , 50 In this review, we discuss the data that led to the development of an array of therapeutics that are aimed at targeting … senescence? …

WATCH VIDEO ABSTRACT: Dermatoporosis: Strategies for Rebuilding the Extracellular Matrix of the Skin.

Dermatoporosis as a disease entity is relatively newly described, the title conceived as recently as 2007. The background of chronic skin fragility, bruising, and atrophy appears to start in some patients as early as their mid-forties, but is full blown over the age of 65 years. The dehydration and fragility of the skin with recurrent bruising and breakdown were initially attributed to increased vessel fragility and permeability thought to be associated with inherent vascular tissue defects in a milieu of increased inflammation and extracellular matrix (ECM) degradation. It has subsequently be

Sirt3 mediates the benefits of exercise on bone in aged mice.

Exercise in later life is important for bone health and delays the progression of osteoporotic bone loss. Osteocytes are the major bone cells responsible for transforming mechanical stimuli into cellular signals through their highly specialized lacunocanalicular networks (LCN). Osteocyte activity and LCN degenerate with aging, thus might impair the effectiveness of exercise on bone health; however, the underlying mechanism and clinical implications remain elusive. Herein, we showed that deletion of Sirt3 in osteocytes could impair the formation of osteocyte dendritic processes and inhibit bone

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases.

Sirtuins are NAD+ dependent histone deacetylases (HDAC) that play a pivotal role in neuroprotection and cellular senescence. SIRT1-7 are different homologs from sirtuins. They play a prominent role in many aspects of physiology and regulate crucial proteins. Modulation of sirtuins can thus be utilized as a therapeutic target for metabolic disorders. Neurological diseases have distinct clinical manifestations but are mainly age-associated and due to loss of protein homeostasis. Sirtuins mediate several life extension pathways and brain functions that may allow therapeutic intervention for age-r…

Telomere Signaling and Maintenance Pathways in Spermatozoa of Infertile Men Treated With Antioxidants: An in silico Approach Using Bioinformatic Analysis.

Telomere shortening is considered as a marker of cellular senescence and it is regulated by various signaling pathways. Sperm telomere appears to play important role in its longevity and function. Antioxidant intake has been known to prevent the shortening of telomere. In the management of male infertility, antioxidants are commonly used to counterbalance the seminal oxidative stress. It is important to understand how antioxidants treatment may modulate telomere signaling in sperm. In the current study, we have identified 377 sperm proteins regulated by antioxidants based on data mining of pub…

Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways.

Targeted therapy and immunotherapy have greatly improved the prognosis of patients with metastatic melanoma, but resistance to these therapeutic modalities limits the percentage of patients with long-lasting responses. Accumulating evidence indicates that a persisting subpopulation of melanoma cells contributes to resistance to targeted therapy or immunotherapy, even in patients who initially have a therapeutic response; however, the root mechanism of resistance remains elusive. To address this problem, we propose a new model, in which dynamic fluctuations of protein expression at the single-c

Matricellular protein CCN1/CYR61: a new player in inflammation and leukocyte trafficking.

Cystein-rich protein 61 (CYR61/CCN1) is a component of the extracellular matrix, which is produced and secreted by several cell types including endothelial cells, fibroblasts and smooth muscle cells. CCN1 has been implicated in leukocyte migration and the inflammatory process, but it is also involved in cardiovascular development and carcinogenesis. It exerts its functions through binding to multiple integrins present in many different cell types. This multiplicity in function is now known to contribute to the diverse array of cellular processes it can regulate. The expression of CCN1 is tight

A different approach to telomere analysis with ddPRINS in chronic lymphocytic leukemia.

Telomeric sequences, located at the very end of the chromosomes, compensate for the chromosomal shortening as it happens after each round of cell division. Telomeric sequences influence the progress of cellular senescence and cancer progression. It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia (CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in pati…

Helicobacter pylori infection: augmentation of telomerase activity in cancer and noncancerous tissues.

Telomerase adds hexameric repeats of 5'-TTAGGG-3' to the ends of chromosomal DNA (telomere) and has been implicated in cell immortalization and cellular senescence. The aim of this study was to measure quantitatively the telomerase activity and human telomerase RNA component (hTR) content in gastric cancer and to examine the relation between these values and histologic factors including Helicobacter pylori as a risk factor for gastric cancer. Telomerase activity was measured by a modified telomeric repeat amplification protocol in cancerous and noncancerous tissues (intestinal metaplasia, chro…

Calcification of matrix vesicles in human aortic valve and aortic media.

Calcification of human aortic valve and aortic media occurs regularly, increases with age, and is distinctively associated with a zone of lipid accumulation. Ultrastructurally, the accumulated lipids are seen as cellular degradation products derived from senescent and degenerate fibrocytes and smooth muscle cells. The products when deposited in the matrix are morphologically similar to the matrix vesicles described in other calcifying tissues, and serve as the initial site of calcification rather than collagen or elastic fibers. Scattered among the smaller and more typical matrix vesicles, the

Persistent CD8+ T cell-driven immune dysregulation despite normalized CD4+ T cell recovery in ART-treated people living with HIV.

BACKGROUND: Despite successful antiretroviral therapy (ART) that restores CD4+ T cell counts and reduces HIV viral loads to undetectable levels, a substantial proportion of people living with HIV (PLWH) exhibit persistent CD4/CD8 ratio inversion. This abnormal ratio is primarily driven by sustained CD8+ T cell expansion and reflects a state of chronic immune dysregulation and incomplete immune recovery. However, cellular and molecular mechanisms underlying this discordant immune state remain poorly understood. METHODS: We analyzed longitudinal data of 5,416 ART-treated PLWH from Shenzhen Thir

Baicalin alleviates uterine inflammaging and improves eggshell quality in aged laying hens.

Aging is a major contributor to the decline in egg quality, with uterine inflammaging playing a key role in this process. Implementing anti- … cally positive area for the age-related protein p53, a component of the p53/p21 pathway involved in cellular senescence, elevated expression levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and decreased messenger RNA (mRNA) expression of the longevity gene sirtuin 1 (SIRT1) (P < 0.05). Additionally, uterine inflam …

Деменция, расстройства настроения и старение.

С повышением возраста и продолжительности жизни в мире как в развитых, так и в развивающихся странах риск развития когнитивных потерь и расстройств настроения значительно возрастает в той мере, в какой после достижения возраста 65, этот риск почти удваивает каждый 5 Спустя годы. В результате, соответствующий рост неинфекционных заболеваний поразит людей со слабоумием и расстройствами настроения, связанными с болезнью Альцгеймера, множественным склерозом, депрессией и тревогой. На клинической основе многочисленные факторы риска и представления, которые связаны с утратой интеллектуальных способн

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… At this point, cellular replication fails and cellular senescence ensues ( Figure 2 ). 5 , 23 Cognitive loss, behavior disorders, and aging have common mechanistic pathways that are intimately connected to one another. … energy homeostasis is lost, the generation of reactive oxygen species (ROS) ensues with oxidative stress, and mitochondrial dysfunction results. 25 In fact, ROS generation also occurs with TL shortening and the development of cellular senescence. 19 , 23 These pathways of cellular senescence become …