1,721,039 research outputs found
Targeting the Unfolded Protein Response with Natural Products: Therapeutic Potential in ER Stress-Related Diseases
Full text linkThis review delves into the intricate relationship between ER stress, the UPR, and human disease, with a specific focus on the therapeutic potential of natural products. We classify and discuss a wide range of natural compounds based on their unique mechanisms of action, whether they act as UPR inhibitors, activators, or indirectly alleviate ER stress by reducing oxidative burden or improving protein folding. By synthesizing the current literature, this review aims to provide a valuable resource for researchers and clinicians, highlighting the most promising natural products and their potential for development into novel therapeutic agents for treating pathologies driven by ER stress
The Interplay Between Ca2+ Homeostasis, Endoplasmic Reticulum Stress, and the Unfolded Protein Response in Human Diseases
Full text linkThe maintenance of endoplasmic reticulum (ER) Ca2+ homeostasis is intrinsically linked to the fidelity of protein folding, forming a functional tether that, when disrupted, triggers the Unfolded Protein Response (UPR). This bidirectional axis serves as a critical rheostat for cellular viability, yet its chronic dysregulation underpins the molecular etiology of numerous pathologies, including neurodegeneration, heart failure, and malignant transformation. This review provides a comprehensive interrogation of the Ca2+-ER Stress–UPR network, delineating how primary stress sensors—PERK, IRE1alpha, and ATF6—engage in complex feedback loops that either reinstate equilibrium or commit the cell to apoptosis. We specifically examine the PERK-CHOP-SERCA2b inhibitory circuit as a central driver of persistent Ca2+ depletion and discuss the role of Mitochondria-Associated Membranes (MAMs) in governing lethal Ca2+ transfer. Notably, we move beyond the classical paradigm of CHOP as a terminal apoptotic executioner, incorporating emerging evidence of its context-dependent adaptive functions. By synthesizing mechanistic insights across diverse disease models, this work highlights the transition from adaptive to maladaptive UPR as a universal pathological checkpoint. Ultimately, we evaluate the therapeutic potential of ‘axis-targeted’ interventions, such as SERCA activators and selective UPR modulators, aimed at resolving the underlying Ca2+ signaling defects in ER stress-related disorders
Natural compounds and anticancer effects: The whole is greater than the sum of its parts
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Unraveling BOLD-100 synergistic potential in pleural mesothelioma treatment: an in vitro study
Full text linkPleural mesothelioma (PM) is a rare cancer affecting the pleural layer on the body’s serosal surfaces. Exposure to asbestos fibers, a naturally occurring fibrous material with insulating characteristics, contributes to PM’s prevalence. PM has a long latency period, making major surgery ineffective and necessitating systemic treatment. Despite the progress of mesothelioma treatment, the median survival is very poor; so, there is a strong need to explore new therapeutic approaches. This study explores the use of BOLD-100, a novel therapeutic drug that targets GRP78, a protein overexpressed in PM cells. BOLD-100, a ruthenium-based small molecule therapeutic drug, is being investigated for the treatment of advanced gastrointestinal malignancies in conjunction with chemotherapy. Our aim is to investigate cellular responses of several PM cell lines to a regimen that includes BOLD-100 in addition to other commonly used treatments. BOLD-100 is a ruthenium-based anticancer therapeutic
The secretome signature of malignant mesothelioma cell lines
No full textThe secretome is the complex set of molecules secreted by cells; these molecules play a key role in cell signaling, communication and migration. Secretomics has been already used to discover new potential diagnostic biomarkers and therapeutic agents and to elucidate key autocrine pathways. Malignant mesothelioma (MMe), an extremely aggressive tumor, is characterized by a long latency period (20-30years), a poor prognosis, and limited effective therapies. MMe has a highly secretory cell type, and the factors released by cells may act in an autocrine or paracrine fashion on tumor and stroma, where they may modulate the extracellular environment. The aim of this work is to characterize the secretome of two MMe cell lines, MM98 and REN, in comparison with a mesothelial cell line Met5A, in order to evaluate differences and similarities of these two different MMe cancer model systems, and to identify potential biomarkers. We performed quantitative shotgun proteomics using SWATH-MS technology and we identified a total of 421 proteins, 112 expressed in the secretome of REN cells, 208 expressed in the secretome of MM98 cells and 189 secreted by mesothelial cells; 25 proteins are shared by the two mesothelioma cell lines
Correlation between Honey Parameters and Wound Healing Properties: The Case of Piedmont (Italy) Samples
No full textIntroduction: Honey possesses several positive properties, making it effective in wound healing mechanisms. However, very little information is available on the different honey types for wound healing activity. Method: In the first "Academy of Sciences", a public engagement project with high school students, we assessed the properties of thirteen kinds of honey from the Piedmont area (Nord West Italy). In particular, we characterized the color intensity (by Pfund scale), total phenolic content (TPC), total flavonoid content (TFC), H2O2 production, and wound closure rate. Results: Then, we tried to verify the presence of a correlation between these parameters, finding a positive correlation between H2O2 and wound closure rate. Conclusion: These data pave the way to characterize different types of Italian honey to completely understand its potential
SCRATCH-AI: A Tool to Predict Honey Wound Healing Properties
Full text linkIn this work, we propose SCRATCH-AI, a tool which relies on interpretable machine learning (ML) methods (namely, Bayesian networks and decision trees) to classify honey samples into wound healing categories. Classification explores the impact of botanical origins (i.e., honey type) and key chemical–biological characteristics such as antioxidant activity on healing, assessed through wound recovery metrics. The obtained classification performance results are very encouraging. Moreover, the models provide non-trivial insights about the causal dependencies of some specific honey features on wound healing properties and show the effect of different honey types (other than the well known Manuka) on cicatrization. The tool is inherently interpretable (due to the chosen ML techniques) and made user-friendly by a carefully designed graphical interface. We believe that the information provided by our tool will allow biologists and clinicians to better utilize honey, with the ultimate goal of leveraging honey capability to accelerate healing and reduce infection risks in clinical practice
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