Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(17)

Published: Aug. 31, 2023

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes these populations vary depending on their spatial distribution within the tissue immunopathologic cues contributing to progression. addition roles structurally supporting organs remodeling tissue, mediate critical interactions immune cells. These have important implications for defining mechanisms identifying potential therapeutic targets. respiratory tract, particular, determine severity outcome numerous acute chronic lung diseases, including asthma, obstructive pulmonary disease, distress syndrome, idiopathic fibrosis. Here, we review studies spatiotemporal identity lung-derived by which regulate responses insult exposures highlight past, current, future targets relevance fibroblast biology context human diseases. This perspective highlights importance fibroblast-immune crosstalk paves way approaches benefit patients disorders.

Language: Английский

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Advances in nanomaterial-targeted treatment of acute lung injury after burns

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 18, 2024

Abstract Acute lung injury ( ALI ) is a common complication in patients with severe burns and has complex pathogenesis high morbidity mortality rates. A variety of drugs have been identified the clinic for treatment ALI, but they toxic side effects caused by easy degradation body distribution throughout body. In recent years, as understanding mechanism underlying improved, scholars developed new nanomaterials that can be safely effectively targeted ALI. Most these methods involve such lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles other nanomaterials, which are to reach tissues perform their functions through active targeting passive targeting, process involves cells organelles. this review, first, mechanisms pathophysiological features occurrence after burn reviewed, potential therapeutic targets summarized, existing classified, possible problems challenges discussed provide reference development

Language: Английский

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The PI3K/Akt-Nrf2 Signaling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4258 - 4276

Published: Jan. 1, 2024

Oxidative stress is a major pathogenic factor in many intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). The Nrf2 signaling pathway mitophagy can reduce reactive oxygen species (ROS) alleviate oxidative stress, but their relationship unclear. Hydroxytyrosol (HT), polyphenolic compound abundant olive oil, has strong antioxidant activity may help treat these diseases. We used pigs model to investigate HT's effect on damage its mechanisms. Diquat (DQ) induced impaired barrier function, which HT mitigated. Mechanistic studies IPEC-J2 cells showed that protected against by activating the PI3K/Akt-Nrf2 promoting mitophagy. Our study highlighted synergistic between mediating effects. Inhibition confirmed disrupting either compromised protective Maintaining redox balance through important for eliminating excess ROS. increases enzymes clear existing ROS, while removes damaged mitochondria reduces ROS generation. This demonstrates pathways collaboratively modulate effects of HT, with neither being dispensable. Targeting could be promising strategy treating stress-related potential treatment.

Language: Английский

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Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review the concepts redox biology and its translational strategy. Glutathione (GSH) is body’s primary detoxifier antioxidant, oxidized form (GSSG) been considered as marker oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure male mice by electrophilic modification dynamin-related protein (Drp1). In healthy exercised hearts, redox-sensitive Cys644 Drp1 highly S-glutathionylated. Nearly 40% normally polysulfidated, which preferential target for GSSG-mediated S-glutathionylation. S-glutathionylation resistant depolysulfidation-dependent mitochondrial hyperfission myocardial dysfunction caused hypoxic stress. MD simulation structure site-directed mutagenetic analysis reveal functional interaction between critical phosphorylation site Ser637, through Glu640. Bulky at via polysulfidation or reduces activity disrupting Ser637-Glu640-Cys644 interaction. Disruption nullifies cardioprotective effect GSSG against after infarction. Our findings suggest therapeutic potential supersulfide-based Cys bulking on disease.

Language: Английский

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GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors

Cancer Research, Journal Year: 2022, Volume and Issue: 82(18), P. 3223 - 3235

Published: July 27, 2022

Abstract Hepatocellular carcinoma (HCC) is one of the primary liver malignancies with a poor prognosis. Glutamic-oxaloacetic transaminase 2 (GOT2) highly tissue-specific gene in liver, but roles GOT2 plays progression HCC remain unclear. Here, we report that downregulated tumor tissues and low expression associated advanced In cells, knockdown promoted proliferation, migration, invasion. mouse models HCC, loss growth as well hematogenous intrahepatic metastasis. Mechanistically, silencing enhanced glutaminolysis, nucleotide synthesis, glutathione synthesis by reprogramming glutamine metabolism to support cellular antioxidant system, which activated PI3K/AKT/mTOR pathway contribute progression. Furthermore, was dependent on sensitive glutaminase inhibitor CB-839 vitro vivo. Overall, involved metabolic promote may serve therapeutic diagnostic target for HCC. Significance: Altered induced supports metastasis confers targetable vulnerability inhibitors.

Language: Английский

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The Multifunctional Family of Mammalian Fatty Acid–Binding Proteins

Annual Review of Nutrition, Journal Year: 2023, Volume and Issue: 43(1), P. 25 - 54

Published: May 19, 2023

Fatty acid-binding proteins (FABPs) are small lipid-binding abundantly expressed in tissues that highly active fatty acid (FA) metabolism. Ten mammalian FABPs have been identified, with tissue-specific expression patterns and conserved tertiary structures. were initially studied as intracellular FA transport proteins. Further investigation has demonstrated their participation lipid metabolism, both directly via regulation of gene expression, signaling within cells expression. There is also evidence they may be secreted functional impact the circulation. It shown FABP ligand binding repertoire extends beyond long-chain FAs properties involve systemic This article reviews present understanding functions apparent roles disease, particularly metabolic inflammation-related disorders cancers.

Language: Английский

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Chemistry and biology of enzymes in protein glutathionylation

Current Opinion in Chemical Biology, Journal Year: 2023, Volume and Issue: 75, P. 102326 - 102326

Published: May 26, 2023

Language: Английский

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Photo‐Activated Oxidative Stress Amplifier: A Strategy for Targeting Glutathione Metabolism and Enhancing ROS‐Mediated Therapy in Triple‐Negative Breast Cancer Treatment

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 3, 2024

Abstract Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple‐negative breast cancer (TNBC). Therefore, development innovative nanomedicines that disrupt redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme CaP mineralized layer, loaded with GSH inhibitor L‐buthionine sulfoximine (BSO), further surface‐modified hyaluronic acid target CD44, is introduced. acidic microenvironment, Ca 2+ initially released, thereby leading to mitochondrial dysfunction eventually triggering apoptosis. Additionally, BSO suppresses synthesis intracellular reduced amplifies level in cells. Furthermore, be activated by near‐infrared light induce photothermal photodynamic effects, causing burst ROS simultaneously promoting cell apoptosis via provoking immunogenic death. The high‐performance effects based on synergistic effect aforementioned multiple damage ablation, are validated TNBC animal models, declaring its potential safe effective anti‐tumor agent. proposed approach offers new perspectives precise efficient treatment

Language: Английский

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Immunotherapy strategies and prospects for acute lung injury: Focus on immune cells and cytokines

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 22, 2022

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a disastrous condition, which can be caused by wide range of diseases, such as pneumonia, sepsis, traumas, and the most recent, COVID-19. Even though we have gained an improved understanding acute pathogenesis treatment mechanism, there still no effective for syndrome, partly responsible unacceptable mortality rate. In injury, inflammatory storm main pathological feature. More more evidences show that immune cells cytokines secreted play irreplaceable role in injury. Therefore, here mainly reviewed various injury from perspective immunotherapy, elaborated crosstalk cytokines, aiming to provide novel ideas targets

Language: Английский

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The Water Extract of Ampelopsis grossedentata Alleviates Oxidative Stress and Intestinal Inflammation

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 547 - 547

Published: Feb. 21, 2023

Oxidative stress is recognized as a significant contributor to the development and progression of inflammation disruptions in balance gut microflora, commonly referred intestinal dysbiosis. It crucial that safe effective antioxidant anti-inflammatory agents are identified address these conditions. Ampelopsis grossedentata, natural plant abundant flavonoids primarily found southern China, has demonstrated potent properties. However, extent which A. grossedentata impact alter composition microbiome remains be fully understood. The purpose this study was explore potential benefits using an agent context inflammation, both vitro vivo. We first conducted initial comparison effects dihydromyricetin (DMY), alcohol extract (AEA, 82% total flavonoids), water (WEA, 57% flavonoids) on cell viability barrier integrity porcine epithelial cells IPEC-J2. Although flavonoid content much lower WEA than AEA, results show they have similar effects. Subsequently, properties were compared with those utilized antioxidants vitro. Lastly, WEA, well its impacts microbiota, evaluated animal models, including mice Drosophila. In summary, our indicate due properties, exhibits protective effect function line Additionally, demonstrates positive correlation DPPH, ABTS radical scavenging rate, FRAP, reducing power under settings. Furthermore, shown effectively alleviate oxidative models by levels pro-inflammatory cytokines increasing enzyme activity liver, activating Nrf2 signaling pathway duodenum. able regulate promoting growth beneficial bacteria inhibiting harmful microbes, extending lifespan Overall, findings suggest may serve valuable dietary supplement for addressing through prebiotic effects, conferred via Nrf2/Keap1 pathway.

Language: Английский

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