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

Oral Nanotherapeutics of Andrographolide/Carbon Monoxide Donor for Synergistically Anti-inflammatory and Pro-resolving Treatment of Ulcerative Colitis DOI
Ying Zhou, Mei Yang, Xiangji Yan

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2023, Номер 15(30), С. 36061 - 36075

Опубликована: Июль 18, 2023

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology affecting the colon and rectum. Current therapeutics are focused on suppressing inflammation but ineffective. Combining anti-inflammatory therapeutic approaches with pro-resolution might be superior strategy for UC treatment. Andrographolide (AG), an active compound from plant Andrographis paniculata, presented effects in various diseases. Gaseous mediators, such as carbon monoxide (CO), have role resolution. Herein, we developed dextran-functionalized PLGA nanocarrier efficient delivery AG donor (CORM-2) synergistically anti-inflammatory/pro-resolving treatment (AG/CORM-2@NP-Dex) based good biocompatibility, slow drug release, targeting, biodegradability. The resulting had nano-scaled diameter ∼200 nm spherical shape. After being coated dextran (Dex), AG/CORM-2@NP-Dex could efficiently internalized by Colon-26 Raw 264.7 cells vitro preferentially localized to inflamed chitosan/alginate hydrogel protection gavage. performed eliminating over-production pro-inflammatory mediator, nitric oxide (NO), down-regulating expression cytokines (TNF-α, IL-1β IL-6), while it showed pro-resolving function accelerating M1 M2 macrophage conversion up-regulating resolution-related genes (IL-10, TGF-β, HO-1). In model, oral administration also effects, therefore relieving effectively. Without appreciable systemic toxicity, this bifunctional represents novel approach expected achieve long-term remission.

Язык: Английский

Процитировано

30

Plant-derived vesicle-like nanoparticles: A new tool for inflammatory bowel disease and colitis-associated cancer treatment DOI

Xue‐Chun Fang,

Junjie Feng,

Xingcheng Zhu

и другие.

Molecular Therapy, Год журнала: 2024, Номер 32(4), С. 890 - 909

Опубликована: Фев. 18, 2024

Язык: Английский

Процитировано

14

The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy DOI
Xin Jiang, Min Yu,

Wei‐Kai Wang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(11), С. 2229 - 2240

Опубликована: Июль 17, 2024

Язык: Английский

Процитировано

14

A targeted proteomics approach reveals a serum protein signature as diagnostic biomarker for resectable gastric cancer DOI Creative Commons
Qiujin Shen, Karol Połom,

Coralie Williams

и другие.

EBioMedicine, Год журнала: 2019, Номер 44, С. 322 - 333

Опубликована: Май 28, 2019

Gastric cancer (GC) is the third leading cause of death. Early detection a key factor to reduce its mortality.We retrospectively collected pre- and postoperative serum samples as well tumour tissues adjacent normal from 100 GC patients. Serum non-cancerous patients were served controls (n = 50). A high-throughput protein technology, multiplex proximity extension assays (PEA), was applied measure levels over 300 proteins. Alteration each analysed by univariate analysis. Elastic-net logistic regression performed select proteins into diagnostic model.We identified 19 (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCP1, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, ADAMTS-15) that together distinguish cases with sensitivity 93%, specificity 100%, area under receiver operating characteristic curve (AUC) 0·99 (95% CI: 0·98-1). Moreover, 19-serum signature provided an increased capacity in at TNM I-II stage (sensitivity 89%, AUC 0·99) high microsatellite instability (MSI) (91%, 98%, compared individual These promising results will inspire large-scale independent cohort study be pursued for validating proposed signature.Based on targeted proteomics elastic-net regression, we which could contribute clinical diagnosis, especially early those MSI. FUND: This supported European H2020-Marie Skłodowska-Curie Innovative Training Networks grant (316,929, GastricGlycoExplorer). Funder had no influence trial design, data evaluation, interpretation.

Язык: Английский

Процитировано

66

Farrerol attenuates β-amyloid-induced oxidative stress and inflammation through Nrf2/Keap1 pathway in a microglia cell line DOI Open Access
Bei Cui, Suli Zhang, Yutao Wang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2018, Номер 109, С. 112 - 119

Опубликована: Ноя. 2, 2018

Farrerol, an important bioactive constituent of rhododendron, exhibits broad activities such as anti-oxidative and anti-inflammatory effects. Recent studies showed that farrerol possesses neuroprotective activity, however, the mechanism has not been reported. The aim present study was to investigate protective effect on β-amyloid (Aβ)-induced mouse microglial BV-2 cells underlying mechanism. were pretreated with for 1 h then subjected Aβ. MTT assay performed measure mitochondrial metabolic activity in cells. production reactive oxygen species (ROS) malondialdehyde (MDA) superoxide dismutase (SOD) detected reflect oxidative stress status. secretion mRNA levels interleukin (IL)-1β (IL-1β), IL-6 tumor necrosis factor-α (TNF-α) measured by ELISA qRT-PCR. expressions NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD (P) H: quinone oxidoreductase (NQO1), Kelch-like ECH-associated protein (Keap1) western blot. Our results improved Aβ-induced Aβ induced ROS MDA, inhibited SOD expression SOD1 SOD2 mRNA, while effects attenuated farrerol. Farrerol also induction IL-6, IL-1β, TNF-α. In addition, enhanced activation Nrf2/Keap1 pathway Knockdown Nrf2 small interfere RNA (siRNA) targeting (si-Nrf2) abolished conclusion, inflammation through enhancing pathway. findings indicated could be considered a therapeutic approach treatment Alzheimer's disease (AD).

Язык: Английский

Процитировано

64

Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus DOI Creative Commons
Chaker El Kalamouni, Étienne Frumence, Sandra Bos

и другие.

Viruses, Год журнала: 2018, Номер 11(1), С. 2 - 2

Опубликована: Дек. 20, 2018

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced response to wide range stress conditions. HO-1 exerts antiviral activity against broad viruses, including Hepatitis C virus, human immunodeficiency and dengue virus by inhibiting viral growth. It has been reported that displays Zika (ZIKV) but mechanisms inhibition remain largely unknown. Using ZIKV RNA replicon with Green Fluorescent Protein (GFP) as reporter protein, we were able show expression resulted replication. Conversely, observed decrease cells replicating replicon. The study infected showed level was significantly lower once replication established, thereby limiting effect HO-1. Our work highlights capacity thwart anti-replicative cells. Therefore, modulation novel therapeutic strategy infection may display limited effect.

Язык: Английский

Процитировано

61

Role of Carbon Monoxide in Host–Gut Microbiome Communication DOI
Christopher Hopper,

Ladie Kimberly De La Cruz,

Kristin V. Lyles

и другие.

Chemical Reviews, Год журнала: 2020, Номер 120(24), С. 13273 - 13311

Опубликована: Окт. 22, 2020

Nature is full of examples symbiotic relationships. The critical relation between host and mutualistic bacteria attracting increasing attention to the degree that gut microbiome proposed by some as a new organ system. exerts its systemic effect through diverse range metabolites, which include gaseous molecules such H2, CO2, NH3, CH4, NO, H2S, CO. In turn, human can influence these well in reciprocal manner. Among molecules, CO occupy special place because their widely known physiological functions overlap similarity both targets functions. roles NO H2S play have been extensively examined others. Herein, host-gut communication are discussion (1) production function CO, (2) available donors research tools, (3) from diet bacterial sources, (4) on including sensing, (5) There large amount literature suggesting "messenger" role communication. However, much more work needed begin achieving systematic understanding this issue.

Язык: Английский

Процитировано

60

Therapeutic Potential of Heme Oxygenase-1 and Carbon Monoxide in Acute Organ Injury, Critical Illness, and Inflammatory Disorders DOI Creative Commons
Stefan W. Ryter

Antioxidants, Год журнала: 2020, Номер 9(11), С. 1153 - 1153

Опубликована: Ноя. 19, 2020

Heme oxygenase-1 (HO-1) is an inducible stress protein that catalyzes the oxidative conversion of heme to carbon monoxide (CO), iron, and biliverdin (BV), latter which converted bilirubin (BR) by reductase. HO-1 has been implicated as a cytoprotectant in various models acute organ injury disease (i.e., lung, kidney, heart, liver). Thus, may serve general therapeutic target inflammatory diseases. function pleiotropic modulator signaling, via removal heme, generation its enzymatic degradation-products. Iron release from HO activity exert pro-inflammatory effects unless sequestered, whereas BV/BR have well-established antioxidant properties. CO, derived activity, identified endogenous mediator can influence mitochondrial and/or cellular signal transduction programs culminate regulation apoptosis, proliferation, inflammation. Much research focused on application low concentration whether administered gaseous form inhalation, or use CO-releasing molecules (CORMs), for benefit disease. The development novel CORMs their translational potential remains active area investigation. Evidence accumulated both CO diseases associated with critical care, including lung injury/acute respiratory distress syndrome (ALI/ARDS), mechanical ventilation-induced injury, pneumonias, sepsis. benefits extend other involving aberrant processes such transplant-associated ischemia/reperfusion chronic graft rejection, metabolic Current planned clinical trials explore ARDS

Язык: Английский

Процитировано

60

Heme Oxygenase-1 in liver transplant ischemia-reperfusion injury: From bench-to-bedside DOI
Hirofumi Hirao, Kenneth J. Dery, Shoichi Kageyama

и другие.

Free Radical Biology and Medicine, Год журнала: 2020, Номер 157, С. 75 - 82

Опубликована: Фев. 19, 2020

Язык: Английский

Процитировано

56

Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway DOI
Xiangyun Li, Jianbo Yu, Lirong Gong

и другие.

Free Radical Biology and Medicine, Год журнала: 2021, Номер 165, С. 243 - 253

Опубликована: Янв. 23, 2021

Язык: Английский

Процитировано

55