Inhibition of interleukin-6 trans-signaling improves survival and prevents cognitive impairment in a mouse model of sepsis DOI Creative Commons

Sufang Jiang,

Dandan Shi,

Long Bai

и другие.

International Immunopharmacology, Год журнала: 2023, Номер 119, С. 110169 - 110169

Опубликована: Апрель 12, 2023

Sepsis-associated encephalopathy (SAE) manifests clinically as acute and chronic cognitive impairments, which is associated with increased morbidity mortality. Interleukin-6 (IL-6), a pro-inflammatory cytokine, consistently up-regulated in sepsis. IL-6 initiates proinflammatory effects after binding to soluble receptor (IL-6R) through trans-signalling, requires the transducer gp130. In this study, we investigated whether inhibition of trans-signalling putative therapeutic target for sepsis SAE. Twenty-five patients (12 septic 13 non-septic patients) were recruited study. A significant increase IL-6, IL-1β, IL-10, IL-8 was observed 24 h ICU admission. animal cecal ligation puncture (CLP) used induce male C57BL/6J mice. One hour before or inducing sepsis, mice treated sgp130, selective trans-signaling inhibitor, respectively. Survival rate, cognition, levels inflammatory cytokines, integrity blood-brain barrier (BBB), oxidative stress assessed. addition, immune cells activation transmigration evaluated peripheral blood brains. Sgp130 improved survival rate functions, reduced including TNF-α, MCP-1, plasma hippocampus (hipp), mitigated BBB disruption, ameliorated sepsis-induced stress. also affected monocytes/macrophages lymphocytes Our results indicate that by sgp130 exerts protective against SAE mouse model suggesting potential strategy.

Язык: Английский

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update DOI Creative Commons
Peter F. Surai, Ivan I. Kochish, В.И. Фисинин

и другие.

Antioxidants, Год журнала: 2019, Номер 8(7), С. 235 - 235

Опубликована: Июль 22, 2019

Poultry in commercial settings are exposed to a range of stressors. A growing body information clearly indicates that excess ROS/RNS production and oxidative stress major detrimental consequences the most common stressors poultry production. During evolution, antioxidant defence systems were developed survive an oxygenated atmosphere. They include complex network internally synthesised (e.g., enzymes, (glutathione) GSH, (coenzyme Q) CoQ) externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants work cooperatively as team maintain optimal redox balance cell/body. This is key element providing necessary conditions for cell signalling, vital process regulation expression various genes, adaptation homeostasis maintenance body. Since considered be important signalling molecules, their concentration strictly regulated by conjunction with transcription factors vitagenes. activation vitagenes via such Nrf2 leads additional synthesis array protective molecules which can deal increased Therefore, it challenging task develop system supplementation help growing/productive birds effective defences On one hand, antioxidants, vitamin or minerals Se, Mn, Cu Zn) compulsory part pre-mixes poultry, and, cases, adequate meet physiological requirements these elements. other due aforementioned commercially relevant stressors, there need support poultry. new direction improving related opportunity activate (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH thioredoxin, Heat shock protein (HSP)/heat factor (HSP), sirtuins, maximise internal AO protection maintenance. development vitagene-regulating nutritional supplements on agenda many companies worldwide.

Язык: Английский

Процитировано

480

Heme Oxygenase-1 Signaling and Redox Homeostasis in Physiopathological Conditions DOI Creative Commons
Valeria Consoli, Valeria Sorrenti,

Salvo Grosso

и другие.

Biomolecules, Год журнала: 2021, Номер 11(4), С. 589 - 589

Опубликована: Апрель 16, 2021

Heme-oxygenase is the enzyme responsible for degradation of endogenous iron protoporphyirin heme; it catalyzes reaction's rate-limiting step, resulting in release carbon monoxide (CO), ferrous ions, and biliverdin (BV), which successively reduced bilirubin (BR) by reductase. Several studies have drawn attention to controversial role HO-1, inducible isoform, pointing out its implications cancer other diseases development, but also underlining importance antioxidant activity. The contribution HO-1 redox homeostasis leads a relevant decrease cells oxidative damage, can be reconducted cytoprotective effects explicated alongside mechanisms involving genes like TIGAR (TP53-induced glycolysis apoptosis regulator), therapeutic functions heme main transformation products, especially has been shown effective on GSH levels implementation sustaining body's response stress. aim this review was collect most knowledge from literature, analyzing different perspectives try put forward hypothesis revealing yet unknown HO-1-involved pathways that could useful promote development new therapeutical strategies, lay foundation further investigation fully understand important system.

Язык: Английский

Процитировано

184

Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy DOI Creative Commons
Cui Liu, Xiangji Yan, Yujie Zhang

и другие.

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Апрель 29, 2022

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing remitting course. The current therapeutics are only modestly effective carry risks for unacceptable adverse events, thus more approaches to treat UC clinically needed.For this purpose, turmeric-derived nanoparticles with specific population (TDNPs 2) were characterized, their targeting ability therapeutic effects against investigated systematically. hydrodynamic size TDNPs 2 was around 178 nm, zeta potential negative (- 21.7 mV). Mass spectrometry identified containing high levels lipids proteins. Notably, curcumin, bioactive constituent turmeric, evidenced in 2. In lipopolysaccharide (LPS)-induced acute inflammation, showed excellent anti-inflammatory antioxidant properties. mice models, we demonstrated that orally administrated could ameliorate accelerate resolution via regulating expression pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, gene, HO-1. Results obtained from transgenic NF-κB-RE-Luc indicated 2-mediated inactivation NF-κB pathway might partially contribute protective effect these particles colitis.Our results suggest edible turmeric represent novel, natural colon-targeting may prevent promote wound repair while outperforming artificial terms low toxicity ease large-scale production.

Язык: Английский

Процитировано

154

The molecular mechanisms of ferroptosis and its role in cardiovascular disease DOI Open Access
Yang Zhang, Laiyun Xin, Mi Xiang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 145, С. 112423 - 112423

Опубликована: Ноя. 17, 2021

Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. shows unique characteristics in biology, chemistry, gene levels, compared to other forms. The metabolic disorder intracellular LOOH catalyzed iron causes the inactivity GPX4, disrupts balance, triggers death. Metabolism amino acid, iron, lipid, including associated pathways, considered as specific hallmark ferroptosis. Epidemiological studies animal experiments have shown that ferroptosis plays an important character pathophysiology cardiovascular disease such atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, abdominal aortic aneurysm (AAA). This review systematically summarized latest research progress on mechanisms Then we report contribution diseases. Finally, discuss analyze therapeutic approaches targeting for with

Язык: Английский

Процитировано

121

Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets DOI Open Access
Konrad Teodor Sawicki, Adam De Jesus, Hossein Ardehali

и другие.

Circulation Research, Год журнала: 2023, Номер 132(3), С. 379 - 396

Опубликована: Фев. 2, 2023

The cardiovascular system requires iron to maintain its high energy demands and metabolic activity. Iron plays a critical role in oxygen transport storage, mitochondrial function, enzyme However, excess is also cardiotoxic due ability catalyze the formation of reactive species promote oxidative damage. While mammalian cells have several redundant import mechanisms, they are equipped with single iron-exporting protein, which makes particularly sensitive overload. As result, levels tightly regulated at many homeostasis. dysregulation ranges from deficiency overload seen types disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, Friedreich's ataxia. Recently, use intravenous therapy has been advocated patients failure certain criteria for deficiency. Here, we provide an overview systemic cellular homeostasis context physiology, deficiency, current therapeutic strategies, future perspectives.

Язык: Английский

Процитировано

68

Long-Term Effects of Polystyrene Nanoplastics in Human Intestinal Caco-2 Cells DOI Creative Commons
Josefa Domenech,

Mariana de Britto,

Antonia Velázquez

и другие.

Biomolecules, Год журнала: 2021, Номер 11(10), С. 1442 - 1442

Опубликована: Окт. 1, 2021

The increasing presence of micro- and nanoplastics (MNPLs) in the environment, their consequent accumulation trophic niches, could pose a potential health threat to humans, especially due chronic ingestion. In vitro studies using human cells are considered pertinent approaches determine risks humans. Nevertheless, most such have been conducted short exposure times high concentrations. Since MNPLs is supposed be chronic, there lack information regarding effects under conditions. To this aim, we assessed outcomes polystyrene nanoparticles (PSNPs), as model MNPLs, undifferentiated Caco-2 (as models cell target ingestion exposures) relevant long-term scenario, consisting eight weeks sub-toxic PSNPs conditions, culture-media was changed every 2–3 days maintain constant exposure. different analyzed endpoints were cytotoxicity, dysregulation stress-related genes, genotoxicity, oxidative DNA damage, intracellular ROS levels. These that showed sensitive enough studies. obtained results attest accumulate through time, inducing changes at ultrastructural molecular minor evaluated genotoxicity-related biomarkers observed. This would indicate no damage or stress observed intestinal after PSNPs. first study dealing with on cultured cells.

Язык: Английский

Процитировано

102

HO-1 Contributes to Luteolin-Triggered Ferroptosis in Clear Cell Renal Cell Carcinoma via Increasing the Labile Iron Pool and Promoting Lipid Peroxidation DOI Creative Commons
Shangting Han, Fangyou Lin, Yucheng Qi

и другие.

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 26

Опубликована: Апрель 25, 2022

Ferroptosis, a novel form of regulated cell death characterized by disrupted iron metabolism and the accumulation lipid peroxides, has exhibited enormous potential in therapy cancer particularly clear renal carcinoma (ccRCC). Luteolin (Lut), natural flavonoid widely existing various fruits vegetables, been proven to exert potent anticancer activity vitro vivo. However, previous studies on mechanism Lut have shown apoptosis but not ferroptosis. In present study, we identified that substantially inhibited survival ccRCC vivo, this phenomenon was accompanied excessively increased intracellular Fe2+ abnormal depletion GSH. addition, induced imbalance mitochondrial membrane potential, classical morphological alterations ferroptosis, generation ROS, occurrence peroxidation an iron-dependent manner cells. these could be reversed some extent ion chelator deferiprone or ferroptosis inhibitor ferrostatin-1, indicating cells treated with underwent Mechanistically, molecular docking further established probably promoted heme degradation labile pool (LIP) upregulating HO-1 expression, which led Fenton reaction, GSH depletion, ccRCC, whereas blocking signaling pathway evidently rescued Lut-induced inhibiting Altogether, current study shows compound monomer exerted efficacy expression activating LIP trigger promising drug candidate for treatment.

Язык: Английский

Процитировано

66

Roles of Heme Oxygenase-1 in Neuroinflammation and Brain Disorders DOI Creative Commons
Yi‐Hsuan Wu, Hsi‐Lung Hsieh

Antioxidants, Год журнала: 2022, Номер 11(5), С. 923 - 923

Опубликована: Май 8, 2022

The heme oxygenase (HO) system is believed to be a crucial mechanism for the nervous under stress conditions. HO degrades carbon monoxide, iron, and biliverdin. These degradation products are involved in modulating cellular redox homeostasis. first identified isoform of system, HO-1, an inducible protein that highly expressed peripheral organs barely detectable brain normal conditions, whereas HO-2 constitutive brain. Several lines evidence indicate HO-1 dysregulation associated with inflammation neurodegeneration, including Parkinson’s Alzheimer’s diseases. In this review, we summarize essential roles plays ensuring health molecular through which dysfunction leads neurodegenerative diseases disruption We also provide summary herbal medicines regulation expression explore current situation regarding remedies disorders.

Язык: Английский

Процитировано

54

Lycopene alleviates di(2-ethylhexyl) phthalate-induced splenic injury by activating P62-Keap1-NRF2 signaling DOI
Xueyan Dai,

Shi‐Yong Zhu,

Jian Chen

и другие.

Food and Chemical Toxicology, Год журнала: 2022, Номер 168, С. 113324 - 113324

Опубликована: Июль 31, 2022

Язык: Английский

Процитировано

48

Isoliquiritin apioside relieves intestinal ischemia/reperfusion-induced acute lung injury by blocking Hif-1α-mediated ferroptosis DOI

Zhou Zhongyin,

Wei Wang,

Juan Xiong

и другие.

International Immunopharmacology, Год журнала: 2022, Номер 108, С. 108852 - 108852

Опубликована: Май 18, 2022

Язык: Английский

Процитировано

44