No – Page 3 – Cell Stress

Endogenous plasma resuspension of peripheral blood mononuclear cells prevents preparative-associated stress that modiﬁes polyA-enriched RNA responses to subsequent acute stressors

INTRODUCTION Cells are impacted by complex and co-occurring stresses throughout a life-course. Our goal was to generate physiologically relevant models of acute cellular stress, initially in relation to 3’ untranslated … Read more

Neuroglobin-enriched secretome provides neuroprotection against hydrogen peroxide and mitochondrial toxin-induced cellular stress

INTRODUCTION Cellular response to stress relies on evolutionary conserved mechanisms aimed at maintaining homeostasis and facilitating adaptation to new cellular environments 1. Under stressful conditions, post-mitotic neurons are hardly replaced. … Read more

Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure

INTRODUCTION Cellular stress is an inherent and inevitable aspect of cell physiology, prompting cells to adapt to environmental changes. Among the distinctive intracellular adaptive responses that have been characterized in … Read more

Dynamics of cell membrane lesions and adaptive conductance under the electrical stress

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reﬂection ﬂuorescence (TIRF) imaging of Ca2+ entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a low 50- to 300-pS conductance, which disappeared instantly once the hyperpolarization was removed. Charging to – 240 mV created high-conductance (> 1 nS) pores which persisted for seconds even at zero membrane potential. With (…)

Saliva, a molecular reﬂection of the human body? Implications for diagnosis and treatment

INTRODUCTION The possibility of using biological fluids such as blood, urine, saliva and other biofluids to diagnose pathologies is a relatively old idea that has taken on a new lease … Read more

CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis?

Metastasis is the leading cause of death in cancer patients. Currently, there are no effective treatments to prevent cancer metastases. Therefore, it is imperative to provide more effective biomarkers and … Read more

Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome

Mechanistic target of rapamycin complex 1 (mTORC1) is a multiprotein complex that serves as a pivotal regulator of cell growth, protein synthesis, metabolism and autophagy [1][2]. This complex compromises mTOR … Read more

The missing hallmark of health: psychosocial adaptation

INTRODUCTION The comprehension of health –defined in a positive fashion rather than as the absence of disease–requires a theory. We recently launched the bases of such a health theory by … Read more

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces (…)

A versatile method for the identification of senolytic compounds

The increased burden of senescent cells is as a well-established hallmark of aging and age-related diseases. This finding sparked significant interest in the identification of molecules capable of selectively eliminating senescent cells, so-called senolytics. Here, we fine-tuned a method for the identification of senolytics that is compatible with high-content fluorescence microscopy. We used spectral detector imaging to measure the emission spectrum of unlabeled control or senescent cells. We observed that senescent cells exhibited higher levels of autofluorescence than their non-senescent counterparts, particularly in the cytoplasmic region. Building on this result, we devised a senolytic assay based on co-culturing quiescent and senescent cells, fluorescently tagged in the nuclear region through the overexpression of H2B-GFP and H2B-RFP, respectively. We validated this approach by showing that first generation senolytics were effective in reducing the (…)