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Plasma endoglin as a marker to predict cardiovascular events in patients with chronic coronary artery diseases.

Recent clinical studies have revealed that the expression of endoglin, an accessory protein for the TGF-β receptor, is increased in patients with atherosclerotic diseases. The plasma endoglin level is thought to represent endothelial activation, inflammation, and senescence. To clarify the significance of plasma endoglin in chronic coronary artery disease. Human umbilical vein endothelial cells (HUVECs) were cultured to examine changes in soluble endoglin (s-endoglin) levels caused by atherogenic stimulation in vitro. We studied 318 patients with stable coronary artery disease who underwent a

Induction of autophagy counteracts the anticancer effect of cisplatin in human esophageal cancer cells with acquired drug resistance.

Cisplatin-based chemotherapy frequently resulted in acquired resistance. The underpinning mechanism of such resistance remains obscure especially in relation to autophagic response. This study thus investigated the role of autophagy in the anticancer activity of cisplatin in human esophageal cancer cells with acquired cisplatin resistance. In response to cisplatin treatment, EC109 cells exhibited substantial apoptosis and senescence whereas cisplatin-resistant EC109/CDDP cells exhibited resistance. In this respect, cisplatin increased ERK phosphorylation whose inhibition by MEK inhibitor signi

RbAp48 is a critical mediator controlling the transforming activity of human papillomavirus type 16 in cervical cancer.

Although human papillomavirus (HPV) infections are the primary cause of cervical cancer, the molecular mechanism by which HPV induces cervical cancer remains largely unclear. We used two-dimensional electrophoresis with mass spectrometry to study protein expression profiling between HPV16-positive cervical mucosa epithelial H8 cells and cervical cancer Caski cells to identify 18 differentially expressed proteins. Among them, retinoblastoma-binding protein 4 (RbAp48) was selected, and its differentiation expression was verified with both additional cervical cancer-derived cell lines and human t

Single-Cell Multiomics Integration Reveals Cell Trajectories and Regulatory Networks in Breast Cancer Progression.

BACKGROUND: Breast cancer is a molecularly heterogeneous disease encompassing distinct subtypes with divergent prognoses and therapeutic responses. Despite extensive bulk genomic characterization, the single-cell transcriptional trajectories, chromatin regulatory landscapes, and intercellular communication networks that drive breast cancer progression from luminal to mesenchymal states remain incompletely understood. Emerging evidence implicates gut microbiome dysbiosis as a systemic modulator of breast cancer risk, immune regulation, and treatment response; however, its coordinated characteri

[Expression profile, immunoregulatory function, and clinical prognostic value of CENPN in breast cancer].

Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic s … small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, …

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics.

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-path

Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge.

The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship is lost when tumorigenic stimuli induce uncontrolled Schwann cell proliferation, generating tumours such us neurofibromas and schwannomas. Schwann cells also re-enter the cell cycle following nerve injury during the process of Wallerian degeneration. In both cases proliferation is finally arrested. We show that in neurofibroma, the induction of Jmjd3 (jumonji domain containing 3, histone lysine demethylase) removes trimethyl groups on lysine-27 of histone-H3 and epigenetically activates the Ink4a/Arf

Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas.

BACKGROUND & AIMS: Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regu

UNC93B1 promotes pancreatic cancer progression through modulation of cGAS-STING signaling.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal solid tumors, largely due to its intricate and immunosuppressive tumor microenvironment (TME). While single-cell sequencing technologies have begun to unravel the cellular heterogeneity of PDAC, a comprehensive understanding of how genetic determinants influence and are influenced by the TME is still lacking. To bridge this knowledge gap, our study employs an integrated multi-omics approach, incorporating single-cell transcriptomics, genomics, and proteomics, complemented by computational biology and machine lear

[Study on the underlying mechanisms of electroacupuncture at "Zusanli" (ST36) in restoring blood glucose homeostasis in prediabetes mice].

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on blood glucose in acute hyperglycemia (AH), low-risk pred … ), eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), p21 (a cell cycle factor in cellular senescence), muscarinic acetylcholine receptor M2 (M2-AchR) and M3-AchR in the pancreatic β-cells were detected using Western blot, and the expression levels of pancreatic and duodenal homeobox factor-1 (PDX-1), beta-cell-specific transcription factor (MAFA) a …

The transcription factor Bhlhb4 is required for rod bipolar cell maturation.

Retinal bipolar cells are essential to the transmission of light information. Although bipolar cell dysfunction can result in blindness, little is known about the factors required for bipolar cell development and functional maturation. The basic helix-loop-helix (bHLH) transcription factor Bhlhb4 was found to be expressed in rod bipolar cells (RB). Electroretinograms (ERGs) in the adult Bhlhb4 knockout (Bhlhb4(-/-)) showed that the loss of Bhlhb4 resulted in disrupted rod signaling and profound retinal dysfunction resembling human congenital stationary night blindness (CSNB), characterized by

Circulating Exosomes Derived-miR-146a from Systemic Lupus Erythematosus Patients Regulates Senescence of Mesenchymal Stem Cells.

The senescence of mesenchymal stem cells (MSCs) plays a crucial role in the development and progression of systemic lupus erythematosus (SLE). Exosomes, small spherical bilayer proteolipid vesicles, contribute to the communication between various cells and their microenvironment by transferring information via their cargo, including the proteins, lipids, and RNAs. While exosomal miRNAs participate in various biological activities, correlations of circulating exosomes with senescent signs of BM-MSCs remain unclear. In our study, we aimed at exploring the roles of circulating exosomal miRNAs in

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… The stimulation of IFN- γ could promote cellular senescence in normal BM-MSCs by activating Jak-Stat signaling [ 9 ]. Similarly, serum from SLE patients obviously promoted umbilical cord (UC) derived-MSCs senescence [ 10 ]. … Activation of nuclear factor-kappa B signalling promotes cellular senescence Oncogene 2011 30 20 2356 2366 2-s2.0-79956148168 10.1038/onc.2010.611 21242976 PMC3080811 28 Wang Y. Zheng F. Gao G. …

Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.

Cancer remains a leading cause of mortality worldwide, with rising incidence and death rates continuing to rise. While conventional treatments such as surgery, radiotherapy, and chemotherapy form the backbone of cancer care, they are often limited by adverse effects, recurrence risk, and incomplete tumor eradication. Tumor immunotherapy-particularly immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapy-has emerged as a transformative approach by activating and reprogramming anti-tumor immune responses. Despite these advances, significant challenges persist, including

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… Notably, cellular senescence in tumor and immune cells critically shapes the immune-resistant TME across these stages. … Combined therapeutic strategies: senolytics and immunotherapy Cellular senescence serves as a double-edged sword in cancer biology. …

Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy.

The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As T cells age, especially within the tumor microenvironment, they undergo significant metabolic shifts that may hinder their proliferation and functionality. This manuscript reviews how metabolic alterations contribute to T cell senescence in cancer and discusses potential therapeutic strategies aimed at reversing these metabolic changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, and lipid metabolism adjustments that co

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… However, the specific mechanisms causing this imbalance in lipid metabolism have not yet been fully elucidated, and the molecular mechanisms by which lipids regulate cellular senescence in T cells also require further exploration. … Janelle V, Neault M, Lebel ME, De Sousa DM, Boulet S, Durrieu L, et al. p16(INK4a) regulates cellular senescence in PD-1-expressing human T cells. Front Immunol. 2021;12:698565. 33. Truong TP, Sakata-Yanagimoto M, Yamada M, Nagae G, Enami T, Nakamoto-Matsubara R, et al. …

Do Cancer and Cancer Treatments Accelerate Aging?

Purpose of reviewThis review focuses on describing the mechanisms and clinical manifestations that underlie accelerated aging associated with cancer and its treatment.Recent findingsThe direct and indirect effects of cancer and its treatment are associated with late occurrence of comorbidities that happen earlier or more frequently in cancer survivors compared to cancer-free individuals, otherwise known as accelerated aging. Use of senolytics and dietary and exercise interventions including prehabilitation, caloric restriction, and rehabilitation are currently under investigation to reverse or

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… Cellular senescence: defined as the stable arrest of the cell cycle. In addition to apoptosis, cellular senescence inhibits unchecked growth of cells. … Campisi J Aging, cellular senescence, and cancer Annu Rev Physiol 2013 75 685 705 23140366 10.1146/annurev-physiol-030212-183653 PMC4166529 17. …

Immunosenescence: signaling pathways, diseases and therapeutic targets.

Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age. Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells. Chronic inflammation contributes to a variety of age-related diseases, such as neurodegenerative disease, cancer, infectious disease, and autoimmune diseases. Although not fully understood, recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellul

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… . 5 , 6 Immune cells are pivotal modulators of cellular senescence. 5 , 7 In this review, we focus on these immune populations, detailing how aging compromises their differentiation and functional capacity, while their dysregulation reciprocally accelerates the senescence process. … senescence 24 . …

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of

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… An integral element of cellular senescence and DOX-related toxicity is DNA damage, the spectrum of which is broad and includes DNA strand breaks, induction of DDR (γ-H2AX), and oxidative modifications [ 233 , 234 ]. … This effect coincided with an induction of cellular senescence, manifested by increased SA-β-Gal, p16, p27, IL-6, and IL-8 [ 244 ]. The current view on the proinflammatory phenotype of DOX-treated SMCs attributes this phenomenon to cellular senescence. …

Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.

Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collect

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… senescence. … Jude Children’s Research Hospital will evaluate two senolytic regimens for their cellular senescence biomarker reduction and frailty improvement in adult survivors of childhood cancer. …

Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan.

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the "geriatric giants", including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation-or "inflammaging"-amplifies systemic decline. Key molecular pathwa

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… A transcriptomic analysis of skeletal muscle revealed that fisetin modulates gene expression linked to cellular senescence, including the downregulation of Cdkn1a and Ddit4 [ 211 ]. … Targeting fundamental aging mechanisms—such as cellular senescence, mitochondrial dysfunction, and immune dysregulation—may yield therapies that not only improve immune function but also extend healthspan and quality of life [ 242 ]. …

Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.

Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer develo

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… This creates a vicious cycle of inflammation and cellular senescence. Prolonged inflammation in organs such as the lungs, liver, and bone marrow can hinder effective clearance, contributing to organ damage and the development of age-related pathologies 16 . … In combination with changes in histone modifications, hypomethylation, especially in repetitive genomic sequences situated within heterochromatic domains, could instigate genomic instability and precipitate early cellular senescence 135 , 136 . …