Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(4), P. e100104 - e100104

Published: Dec. 1, 2024

Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation well-established key factor, recent evidence highlights critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced injury. This review provides comprehensive analysis complex interactions within hepatic microenvironment ALD. It examines contributions both parenchymal cells, like hepatocytes, non-parenchymal such as stellate Kupffer neutrophils, sinusoidal endothelial driving progression disease. Additionally, we explored involvement mediators, including cytokines, chemokines inflammasomes, which regulate inflammatory responses promote injury fibrosis. A particular focus has been placed on extracellular vesicles (EVs) essential mediators intercellular communication beyond liver. These facilitate transfer signalling molecules, microRNAs proteins, modulate immune responses, fibrogenesis lipid metabolism, thereby influencing progression. Moreover, underscore importance organ-to-organ crosstalk, particularly gut-liver axis, where dysbiosis increased intestinal permeability lead to microbial translocation, exacerbating inflammation. The adipose-liver axis also highlighted, impact adipokines free fatty acids from adipose tissue steatosis inflammation context alcohol consumption.

Language: Английский

---

Pyroptosis in Endothelial Cells and Extracellular Vesicle Release in Atherosclerosis via NF-κB-Caspase-4/5-GSDM-D Pathway

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1568 - 1568

Published: Nov. 22, 2024

Background: Pyroptosis, an inflammatory cell death, is involved in the progression of atherosclerosis. Pyroptosis endothelial cells (ECs) and its underlying mechanisms atherosclerosis are poorly understood. Here, we investigated role a caspase-4/5-NF-κB pathway pyroptosis palmitic acid (PA)-stimulated ECs EVs as players pyroptosis. Methods: Human umbilical vein (HUVECs) were cultured medium, treated with Ox-LDL, PA, caspase-4/5 inhibitor, NF-κB sEV release inhibitor for 24 h, respectively. The cytotoxicity PA was determined using MTT assay, migration scratch-wound-healing morphology bright field microscopy, lipid deposition oil red O staining. mRNA protein expression GSDM-D, CASP4, CASP5, NF-κB, NLRP3, IL-1β, IL-18 RT-PCR Western blot. Immunofluorescence used to determine NLRP3 ICAM-1 expressions. Extracellular vesicles (EVs) isolated exosome isolation kit characterized by blot scanning electron microscopy. Results: stimulation significantly changed HUVECs swelling, plasma membrane rupture, increased LDH release, which features accumulation reduced migration. also triggered inflammation dysfunction, evidenced activation, upregulation (endothelial activation marker), pyroptotic markers (NLRP3, IL-18). Inhibition (Ac-FLTD-CMK) (trifluoroacetate salt (TFA)) resulted significant reduction caspase-4/5, gasdermin D (GSDM-D) PA-treated HUVECs. Furthermore, GW4869, markedly PA-stimulated derived from exacerbated pyroptosis, indicated augmented NF-κB. Conclusions: present study revealed that inflammatory, non-canonical signaling may be one crucial mechanistic pathways associated ECs, facilitated normal during

Language: Английский

---

A Pyroptosis Radiosensitizer Facilitates Hypoxic Tumor Necrosis

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Hypoxia-related tumor radioresistance markedly impairs the efficacy of radiotherapy. Herein, a targeted radiosensitization strategy is introduced, leveraging upregulation gasdermin C (GSDMC) in hypoxic cells, aiming to induce pyroptosis through application cobalt-containing polyoxometalate-based radiosensitizer. This novel radiosensitizer designed for precisely controlled release cobalt ions upon X-ray irradiation, thereby activating caspase-8 and prompting cleavage GSDMC. sequence events selectively triggers directly addressing radioresistance. The ensuing results highlight enhanced radiotherapy necrosis both vitro vivo models. Overall, findings confirm effectiveness this targeting high GSDMC expression tumors precise Such encourage further exploration hypoxia-driven improve cancer treatment outcomes.

Language: Английский

---

Advances in the Regulation of Hematopoietic Homeostasis by Programmed Cell Death Under Radiation Conditions

Stem Cell Reviews and Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Language: Английский

---

Harnessing Viral Proteases for Cellular and Molecular Engineering

Chemistry - Methods, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Viral proteases (VIPs) are naturally evolved enzymes that cleave viral polyproteins into functional proteins with remarkable specificity, orthogonality, and minimal cytotoxicity in mammalian cells. These unique properties have positioned VIPs as indispensable tools synthetic biology, enabling precise programmable control of protein activity. By recognizing defined cleavage sites, VIP‐based systems can facilitate targeted release or degradation, driving innovations the design genetically encoded sensors actuators. Engineered VIP been applied to record dynamic cellular events, modulate signaling pathways, regulate gene expression high precision. Their versatility reliability unlocked transformative applications across diverse fields, including neural circuit mapping, high‐throughput drug discovery, cancer therapies. The exceptional precision, robustness, safety continue advance their role cornerstone technologies thereby empowering creation next‐generation molecular therapeutic innovation.

Language: Английский

---

Potential reverse functions of GOLPH3 and GOLPH3L in pyroptotic cell death, with implications in resistance to radiotherapy and chemotherapy

Human Cell, Journal Year: 2025, Volume and Issue: 38(4)

Published: May 22, 2025

Language: Английский

---

Maresin1 alleviates neuroinflammation by inhibiting caspase-3/ GSDME-mediated pyroptosis in mice cerebral ischemia-reperfusion model

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2024, Volume and Issue: 33(8), P. 107789 - 107789

Published: May 22, 2024

To explore the mechanism of Maresin1 in reducing cerebral ischemia-reperfusion injury.

Language: Английский

---

Regulator of G protein signaling 20 contributes to radioresistance of non-small cell lung cancer cells by suppressing pyroptosis

Radiation Medicine and Protection, Journal Year: 2024, Volume and Issue: 5(3), P. 178 - 184

Published: May 23, 2024

Radioresistance is a major challenge for radiotherapy of lung cancer. Pyroptosis novel form immunogenic cell death. This study investigated the potential role regulator G protein signaling 20 (RGS20) in radioresistance non-small cancer (NSCLC) by alleviating GSDMD-mediated pyroptosis. A total 35 adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA), who underwent radiotherapy, were enrolled and divided into radiosensitive (n=16) radioresistant (n=19) groups based on clinical prognosis. expression prognosis RGS20 analyzed Gene Expression Profiling Interactive Analysis (GEPIA) database. line (A549R) was constructed irradiating A549 cells with 6 Gy X-ray/day 10 fractions. Cell survival measured colony formation assay. regulatory effect pyroptosis verified LDH release western blot assay, underlying mechanism introducing siRNA inhibitor. 2181 differentially expressed genes (DEGs) identified analyzing data individuals TCGA-LUAD dataset. These DEGs enriched alpha (z) signalling events Reactome exhibited significant upregulation among DEGs, its higher predicted poor LUAD patients. In vitro, increased irradiation cells, whereas it remained at much high levels A549R regardless irradiation. GSDMD‐dependent markedly lower than that cells. Furthermore, knockdown gene significantly radiosensitivity suppression contributes to NSCLC which might be target radiotherapy.

Language: Английский

---

Pore formation at the lytic synapse triggers the canonical pyroptotic cell death pathway

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

Prokaryotic pore-forming toxins drive inflammasome activation and pyroptosis through K+-dependent of the canonical NLRP3/caspase-1/gasdermin D signaling axis. In this study, we hypothesized that perforin, a eukaryotic protein released into lytic synapse by antigen-specific cytotoxic T lymphocytes (CTLs) upon cognate antigen recognition, mimics pro-pyroptotic activity ancestral toxins, complementing its role as conduit for granzymes. Utilizing imaging molecular approaches, demonstrate perforation target cells CTL attack elicits swift K+ efflux followed NLRP3-dependent proinflammatory caspase-1 major substrate, pyroptotic executioner gasdermin (GSDMD). Acute cell death is gasdermin-dependent demonstrates morphological features pyroptosis, including body formation, bloating, plasma membrane rupture, release intracellular contents; contrast, sustained interaction with CTLs unmasks delayed apoptotic phenotype in remaining cells. Perforation soluble perforin sufficient to trigger rapid efflux, activation, pyroptosis. Our results reveal novel mechanism engagement machinery attack, which itself can autonomously engage programmed (PCD), highlighting complexity diversity arsenal.

Language: Английский

---

Inhibition of GZMB activity ameliorates cognitive dysfunction by reducing demyelination in diabetic mice

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

---