Txnip AND nrf2

ETHNOPHARMACOLOGICAL RELEVANCE: Exocarpium Citri Grandis (ECG), the epicarp of C. grandis 'Tomentosa' which is also known as Hua-Ju-Hong in China, has been widely used for thousands of years to treat inflammatory lung disorders such as asthma, and cough as well as dispelling phlegm. However, its underlying pharmacological mechanisms in acute lung injury (ALI) remain unclear. AIM OF THE STUDY: To explore the therapeutic effect of ECG on ALI and reveal the potential mechanisms based on experimental techniques in vivo and in vitro...

Pyroptosis, a type of programmed cell death, is characterized by cell swelling with bubbles, and the release of inflammatory cell cytokines. Piperlongumine (PL) is a natural bioactive product extracted from Piper longum L, which can effectively exert anti-tumor activities in cancer. However, the effects and the exact molecular mechanisms of PL in esophageal squamous carcinoma (ESCC) remain unclear. This research aimed to investigate the role and mechanism of PL on ESCC in vitro and in vivo. In vitro, the MTT results showed that the IC50 of PL in ESCC cells was 28...

The review considers modern data on the mechanisms of activation and redox regulation of the NLRP3 inflammasome and gasdermins, as well as the role of selenium in these processes. Activation of the inflammasome and pyroptosis represent an evolutionarily conserved mechanism of the defense against pathogens, described for various types of cells and tissues (macrophages and monocytes, microglial cells and astrocytes, podocytes and parenchymal cells of the kidneys, periodontal tissues, osteoclasts and osteoblasts, as well as cells of the digestive and urogenital systems, etc...

Cisplatin (Cis) is among the most powerful antineoplastic medications, nevertheless, its serious side effects; particularly nephrotoxicity designates a major concern. Previous studies reported that ezetimibe (Eze), a well-known antihyperlipidemic drug, exerts additional trivial pharmacological effects. In this work, we displayed Eze as an intriguing protective candidate in a cisplatin-induced nephrotoxicity rat model through AMPK activation. Eze (10 mg/kg, p.o.) was administered for two weeks and Cis (10 mg/kg, i...

Cholera is an exceptionally aggressive infectious disease characterized by the potential to induce acute, copious, watery diarrhea of considerable severity and renal inflammation. Diabetic nephropathy is a serious complication of diabetes mellitus that can lead to kidney failure through inflammation; thus, anti-inflammatory agents are promising therapies for diabetic nephropathy. Previous studies have shown that the essential oil of Zanthoxylum myriacanthum var. pubescens Huang, Maqian essential oil (MQEO), exhibits potent antibacterial, anti-inflammatory, and renoprotective activities in diabetic mice and has emerged as a potential therapeutic drug for the treatment of diabetic nephropathy complications...

OBJECTIVE: Mitochondrial oxidative stress is an important factor in infertility. The mitochondrial thioredoxin system plays an important role in this condition. N-acetyl-5-methoxy tryptamine (melatonin) plays a role in reducing oxidative stress and apoptosis in spermatogonial stem cells (SSCs). In this study, we explore the probable protective effects of melatonin on the mitochondrial thioredoxin system [thioredoxin 2 (Trx2)/Txnip] in SSCs under oxidative stress. MATERIALS AND METHODS: In this experimental study, SSCs were co-cultured two-dimensionally (2D) with Sertoli cells in DMEM culture medium that contained 10% fetal bovine serum (FBS), 1% antibiotics, and 10 ng/ml glial cell-derived neurotrophic factor (GDNF) for 30 days...

Bardoxolone methyl, which triggers nuclear factor erythroid 2-related factor (Nrf2), has therapeutic effects against myocardial infarction, heart failure, and other diseases. Nrf2 can inhibit the activation of the thioredoxin-interacting protein (TXNIP)/NLR family pyrin domain-containing protein 3 (NLRP3) pathway. Doxorubicin is an anthracycline chemotherapeutic drug associated with cardiotoxicity, limiting its clinical use. In this study, we explored the specific mechanism of the Nrf2-TXNIP-NLRP3 pathway in doxorubicin-induced cardiotoxicity using bardoxolone methyl in animal and cell models...

Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, plays a crucial role in controlling inflammation and neovascularization. However, the potential role of Gal-1 in preventing myocarditis remains uncertain. We aimed to explore the functions and mechanisms of Gal-1 in preventing myocarditis. In vivo, C57/BL6 mice were pre-treated with or without Gal-1 and then exposed to lipopolysaccharide (LPS) to induce myocarditis. Subsequently, cardiac function, histopathology, inflammation, oxidative stress, and apoptosis of myocardial tissues were detected...

Thioredoxin-interacting protein (TXNIP) is sensitive to oxidative stress and is involved in the pathogenesis of various metabolic, cardiovascular, and neurodegenerative disorders. Therefore, several studies have suggested that TXNIP is a promising therapeutic target for several diseases, particularly cancer and diabetes. However, the regulation of TXNIP expression under amino acid (AA)-restricted conditions is not well understood. In the present study, we demonstrated that TXNIP expression was promoted by the deprivation of AAs, especially arginine, glutamine, lysine, and methionine, in non-small cell lung cancer (NSCLC) cells...

BACKGROUND: Maresin1 (MaR1) is a potent lipid mediator that exhibits significant anti-inflammatory activity in the context of several inflammatory diseases. A previous study reported that MaR1 could suppress MSU crystal-induced peritonitis in mice. To date, the molecular mechanism by which MaR1 inhibits MSU crystal-induced inflammation remains poorly understood. METHODS: Mousebone marrow-derived macrophages (BMDMs) were pretreated with MaR1 and then stimulated with FAs (palmitic, C16:0 and stearic, C18:0) plus MSU crystals (FAs + MSUc)...

BACKGROUND: Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown. METHODS: In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18...

Apoptotic death of retinal ganglion cells (RGCs) is a common pathologic feature in different types of optic neuropathy, including ischemic optic neuropathy and glaucoma, ultimately leading to irreversible visual function loss. Potent and effective protection against RGC death is determinative in developing a successful treatment for these optic neuropathies. This study evaluated the neuroprotective effect of a HECT domain-E3 ubiquitin ligase inhibitor, M01, on retinal ganglion cells after ischemic injury. Experimental anterior ischemic optic neuropathy (AION) was induced by photothrombotic occlusion of microvessels supplying optic nerve in rats...

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens in the global swine industry over the past three decades. There is no licensed antiviral medication that can effectively control this infection. In the present study, the structure of SP-1 isolated and purified from Sargassum weizhouense was analyzed, and its antioxidant capacity and antiviral effect in MARC-145 cells against PRRSV were investigated. The results showed that SP-1 is a novel polysaccharide which mainly is composed of →4)-β-D-ManpA-(1→, →4)-α-L-GulpA-(1→ and a small amount of →4)-β-D-GalpA-(1→...

Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1β, GM-CSF, and 8-OHdG...

Our previous data have revealed TCP particles caused cell death of osteocytes, comprising over 95% of all bone cells, which contribute to periprosthetic osteolysis, joint loosening and implant failure, but its mechanisms are not fully understood. Here, we reported that TCP particles inhibited cell viability of osteocytes MLO-Y4, and caused cell death. TCP particles caused mitochondrial impairment and increased expressions of LC-3 II, Parkin and PINK 1, accompanied by the elevation of autophagy flux and intracellular acidic components, the accumulation of LC-3II, PINK1 and Parkin in damaged mitochondria, and p62 reduction...

Low back pain is usually caused by intervertebral disc degeneration (IVDD), during which the involvement of oxidation system imbalance and inflammasome activation cannot be neglected. In this study, we aimed to validate the expression level of TXNIP in IVDD and investigate the function and potential mechanism of action of verapamil. TXNIP is upregulated in the degenerate nucleus pulposus in both humans and rats, as well as in tert-butyl hydroperoxide (TBHP)-stimulated nucleus pulposus cells. Administration of verapamil, a classic clinical drug, mitigated the TBHP-induced overproduction of reactive oxygen species and activation of the NLRP3 inflammasome, thus protecting cells from pyroptosis, apoptosis, and extracellular matrix degradation...

[This retracts the article DOI: 10.1155/2022/9088727.].

Pesticide mixtures can reduce pest resistance, however, their overuse severely threatens aquatic animal survival and public health. Avermectin (AVM) and imidacloprid (IMI) are potent insecticides often employed in agriculture. By inducing oxidative stress, these chemicals can induce cell death. Here, we evaluated the combined toxicity of AVM and IMI on EPC cells based on the concept of toxicity units (TU). We established EPC cell models exposed to AVM and IMI alone and in combination. The results showed that AVM and IMI had additive effects on the toxicity of EPC cells...

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria-coptis herb couple (SC) is a classic herbal pair used in many Traditional Chinese Medicine (TCM) formulations in the treatment of endocrine and metabolic deseases. Diabetes mellitus and non-alcoholic steatohepatitis (NASH) are both endocrine and metabolic diseases. Previous studies have shown that SC has anti-diabetic effects. However, the effect and mechanism of SC against NASH remains unclear. AIM OF THE STUDY: This study aimed to demonstrate the effect and mechanism of SC against NASH through the nuclear factor-erythroid 2-related factor 2 (Nrf2) and farnesoid X receptor (FXR) dual signaling pathways in vivo and in vitro...

Copper (Cu) is one of the most significant trace elements in the body, but it is also a widespread environmental toxicant health. Ferroptosis is a newly identified programmed cell death, which involves various heavy metal-induced organ toxicity. Nevertheless, the role of ferroptosis in Cu-induced hepatotoxicity remains poorly understood. In this study, we found that 330 mg/kg Cu could disrupt the liver structure and cause characteristic morphological changes in mitochondria associated with ferroptosis. Additionally, Cu treatment increased MDA (malondialdehyde) and LPO (lipid peroxide) production while reducing GSH (reduced glutathione) content and GCL (glutamate cysteine ligase) activity...