sr9009

Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecular mechanisms underlying the interplay between the circadian clock and the immune system in modulating infection processes are incompletely understood. Here, we demonstrate that NLRP6, a novel nucleotide-oligomerization domain (NOD)-like receptor (NLR) family member highly expressed in the intestine, is closely associated with the differential day-night response to Salmonella infection...

AIM: Rev-erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev-erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev-erbα in experimental RAP and to explore the relationship between Rev-erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments...

Because inflammation in chondrocytes contributes to the induction of osteoarthritis (OA), regulation of their activity is essential. A previous study showed that stimulation of the reverse erythroblastosis virus (REV-ERB) nuclear receptors in spinal glial cells elicits anti-inflammatory and antinociception effects in animal models of chronic pain. However, the involvement of REV-ERBs in chondrocyte functions and OA pathologies remains to be elucidated. In the current study, we found that pretreatment with the REV-ERB agonist SR9009 significantly blocked the increases in inflammatory molecules [(matrix metalloproteinase (MMP) 3, MMP9, and MMP13] and cytokines (interleukin-1β and tumor necrosis factor) in primary cultured chondrocytes following treatment with lipopolysaccharide...

BACKGROUND: Proteasome inhibitors, such as bortezomib, have demonstrated efficacy in the therapeutic management of multiple myeloma (MM). However, it is important to note that these inhibitors also elicit endoplasmic reticulum stress, which subsequently triggers the unfolded protein response (UPR) and autophagy, which have been shown to facilitate the survival of tumor cells. The disruption of the circadian clock is considered a characteristic feature of cancer. However, how disrupted circadian clock intertwines with tumor metabolism and drug resistance is not clearly clarified...

BACKGROUND: The dysregulation of local circadian clock has been implicated in the pathogenesis of a broad spectrum of diseases. However, the pathophysiological role of intrinsic circadian clocks Rev-Erbα in ischemia-reperfusion (IR)-induced acute lung injury (ALI) remains unclear. METHODS: The IR-ALI model was established by subjecting isolated perfused rat lungs to 40 min of ischemia followed by 60 min of reperfusion. Rats were randomly assigned to one of six groups: control, control + SR9009 (Rev-Erbα agonist, 50 mg/kg), IR, and IR + SR9009 at one of three dosages (12...

BACKGROUND: Ulcerative colitis (UC) is a chronic, incurable condition characterized by mucosal inflammation and intestinal epithelial cell (IEC) damage. The circadian clock gene NR1D1, implicated in UC and the critical mitophagy process for epithelial repair, needs further exploration regarding its role in mitophagy regulation in UC. METHODS: We created a jet lag mouse model and induced colitis with dextran sulfate sodium (DSS), investigating NR1D1's role. Intestinal-specific Nr1d1 knockout mice were also generated...

Trophoblast plays a crucial role in gestation maintenance and embryo implantation, partly due to the synthesis of progesterone. It has been demonstrated that hypoxia regulates invasion, proliferation, and differentiation of trophoblast cells. Additionally, human trophoblasts display rhythmic expression of circadian clock genes. However, it remains unclear if the circadian clock system is present in goat trophoblast cells (GTCs), and its involvement in hypoxia regulation of steroid hormone synthesis remains elusive...

UNLABELLED: Potentiating antitumor immunity is a promising therapeutic approach for treating a variety of cancers, including breast cancer. One potential strategy to promote antitumor immunity is targeting DNA damage response. Given that the nuclear receptor NR1D1 (also known as REV-ERBα) inhibits DNA repair in breast cancer cells, we explored the role of NR1D1 in antitumor CD8+ T-cell responses. First, deletion of Nr1d1 in MMTV-PyMT transgenic mice resulted in increased tumor growth and lung metastasis...

The REV-ERBα nuclear receptor is a key component of the molecular machinery of circadian oscillators in mammals. While the rhythmic expression of this receptor has been described in teleosts, several critical aspects of its regulation remain unknown, such as which synchronizers entrain its rhythm, and whether it can modulate the expression of other clock genes. The objective of this study was to gain deeper understanding of the role of REV-ERBα in the fish circadian system. To this end, we first investigated the cues that entrain the rhythm of rev-erbα expression in the goldfish (Carassius auratus) liver and hypothalamus...

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by excessive scarring of the lungs that can lead to respiratory failure and death. Lungs of patients with IPF demonstrate excessive deposition of extracellular matrix (ECM) and an increased presence of pro-fibrotic mediators such as transforming growth factor-beta 1 (TGFβ1), which is a major driver of fibroblast-to-myofibroblast transition (FMT). Current literature supports that circadian clock dysfunction plays an essential role in the pathophysiology of various chronic inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease, and IPF...

PURPOSE: To explore the role of circadian clock gene NR1D1 (REV-erbα) in bladder cancer (BC). METHODS: Firstly, the association of NR1D1 level with clinical characteristics and prognosis was investigated among patients diagnosed with BC. Secondly, CCK-8, transwell, and colony formation experiments were performed among BC cells treated with Rev-erbα agonist (SR9009), as well as lentivirus and siRNA, for which NR1D1 were overexpressed (OE) and knocked down (KD), respectively...

The circadian clock is involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), and the target pathways of many NASH candidate drugs are controlled by the circadian clock. However, the application of chronopharmacology in NASH is little considered currently. Here, the time-dependent effect of REV-ERBα agonist SR9009 on diet-induced NASH and microbiota was investigated. C57BL/6J mice were fed a high-cholesterol and high-fat diet (CL) for 12 weeks to induce NASH and then treated with SR9009 either at Zeitgeber time 0 (ZT0) or ZT12 for another 6 weeks...

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients...

Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathways that control susceptibility, injury, and recovery in the neurological disorders. Emerging evidence suggest that Rev-erbα plays a key role in the inflammation and oxidative stress, two pivotal mechanisms in the pathogenesis, progression, and recovery process of ischemic stroke. However, it remains inconclusive whether Rev-erbα activation is protective against ischemic brain damage...

Renewal of retinal photoreceptor outer segments is conducted through daily shedding of distal photoreceptor outer segment tips and subsequent their phagocytosis by the adjacent retinal pigment epithelium (RPE) monolayer. Dysregulation of the diurnal clearance of photoreceptor outer segment tips has been implicated in age-related retinal degeneration, but it remains to be clarified how the circadian phagocytic activity of RPE cells is modulated by senescence. In this study, we used the human RPE cell line ARPE-19 to investigate whether hydrogen peroxide (H2 O2 )-induced senescence in ARPE-19 cells alters the circadian rhythm of their phagocytic activity...

Molecular clock REV-ERBα is central to regulating lung injuries, and decreased REV-ERBα abundance mediates sensitivity to pro-fibrotic insults and exacerbates fibrotic progression. In this study, we determine the role of REV-ERBα in fibrogenesis induced by bleomycin and Influenza A virus (IAV). Bleomycin exposure decreases the abundance of REV-ERBα, and mice dosed with bleomycin at night display exacerbated lung fibrogenesis. Rev-erbα agonist (SR9009) treatment prevents bleomycin induced collagen overexpression in mice...

BACKGROUND: Doxorubicin-induced cardiotoxicity has been closely concerned in clinical practice. Rev-erb α is a transcriptional repressor that emerges as a drug target for heart diseases recently. This study is aimed at investigating the role and mechanism of Rev-erb α in doxorubicin-induced cardiotoxicity. METHODS: H9c2 cells were treated with 1.5  μ M doxorubicin, and C57BL/6 mice were treated with a 20 mg/kg cumulative dose of doxorubicin to construct doxorubicin-induced cardiotoxicity models in vitro and in vivo...

BACKGROUND: In-stent restenosis hardly limits the therapeutic effect of the percutaneous vascular intervention. Although the restenosis is significantly ameliorated after the application of new drug-eluting stents, the incidence of restenosis remains at a high level. OBJECTIVE: Vascular adventitial fibroblasts (AFs) play an important role in intimal hyperplasia and subsequent restenosis. The current study was aimed to investigate the role of nuclear receptor subfamily 1, group D, member 1 (NR1D1) in the vascular intimal hyperplasia...

Subarachnoid hemorrhage (SAH) is associated with circadian rhythm abnormalities, in which REV-ERBα plays a major regulatory role. Our ambition was to investigate the capacity of REV-ERBα to inhibit neuronal neuroapoptosis induced by early brain injury (EBI) after SAH. The endovascular perforation model was used to produce experimental SAH in Sprague-Dawley rats. Specific small-interfering RNA was used to downregulate the expression REV-ERBα while SR9009 was used to upregulate the expression before assessments...

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-β1 (TGF-β1) were used to establish models of cardiac fibrosis...