Iron overload-dependent ferroptosis is believed to contribute to the brain injury of ischemia/reperfusion (I/R), whereas toll-like receptor 4 (TLR4) can exert pro-ferroptosis effect via inhibiting the glutathione peroxidase 4 (GPX4) level, but the mechanisms behind these phenomenon are not fully elucidated. Tumor necrosis factor receptor correlated factor 3-interaction Jun amino-terminal kinase [JNK]-activating modulator (T3JAM) can activate specific molecule and its downstream signaling pathways, including TLR4. This study aims to explore whether targeting T3JAM can reduce I/R-induced ferroptosis in brain via downregulating TLR4.
View Article and Find Full Text PDFLi Qi Huo Xue Di Wan (LQHXDW), a Chinese herbal medicine, is commonly used to treat symptoms such as palpitations, chest tightness, chest pain, and shortness of breath. However, its potential to reduce ischemia or hypoxia-induced cardiac injury and remodeling, along with the precise mechanisms involved, remains unclear. This study aims to investigate the effects of LQHXDW on cardiac injury and remodeling induced by ischemia or hypoxia, both in vivo and in vitro, and to elucidate the underlying mechanisms.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
September 2024
Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. The mice received a single injection of DOX (15 mg/kg, i.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
November 2023
Copper is a trace element essential for the maintenance of normal physiological functions in cardiovascular system, and its transport and metabolisms are regulated by various copper proteins such as copper-based enzymes, copper chaperones and copper transporters. The disturbance of copper level or abnormal expression of copper proteins are closely associated with the development of cardiovascular diseases such as atherosclerosis, hypertension, ischemic heart disease, myocardial hypertrophy and heart failure. Thus, intervention of copper ion signaling pathways is expected to be an effective measure for treating cardiovascular diseases.
View Article and Find Full Text PDFBreast cancer and osteosarcoma are common cancers in women and children, respectively, but ideal drugs for treating patients with breast cancer or osteosarcoma remain to be found. Micafungin is an antifungal drug with antitumor activity on leukemia. Based on the notion of drug repurposing, this study aims to evaluate the antitumor effects of micafungin on breast cancer and osteosarcoma in vitro and in vivo, and to elucidate the underlying mechanisms.
View Article and Find Full Text PDFMitochondrial dynamics homeostasis is sustained by continuous and balanced fission and fusion, which are determinants of morphology, abundance, biogenesis and mitophagy of mitochondria. Optic atrophy 1 (OPA1), as the only inner mitochondrial membrane fusion protein, plays a key role in stabilizing mitochondrial dynamics. The disturbance of mitochondrial dynamics contributes to the pathophysiological progress of cardiovascular disorders, which are the main cause of death worldwide in recent decades and result in tremendous social burden.
View Article and Find Full Text PDFCarbapenems have been considered to be the preferred antibiotics against thus far. However, carbapenem-resistant (CRAB) has gradually escalated worldwide, and it frequently causes respiratory and bloodstream infections. Its resistance may lead to high mortality.
View Article and Find Full Text PDFSonic hedgehog (SHH) signaling is vital for cell differentiation and proliferation during embryonic development, yet its role in cardiac, cerebral, and vascular pathophysiology is under debate. Recent studies have demonstrated that several compounds of SHH signaling regulate ion channels, which in turn affect the behavior of target cells. Some of these ion channels are involved in the cardio-cerebrovascular system.
View Article and Find Full Text PDFMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis.
View Article and Find Full Text PDFImpaired endothelium-dependent vasodilation in atherosclerosis is a high-risk factor for myocardial infarction and ischemic stroke, and inflammation, necroptosis and apoptosis contribute to endothelial dysfunction in atherosclerosis. Although DL-3-n-butylphthalide (NBP) has been widely used in treating ischemic stroke, its effect on endothelium-dependent vasodilation remains unknown. This study aims to explore whether NBP is able to improve endothelium-dependent vasodilation in atherosclerosis and the underlying mechanisms.
View Article and Find Full Text PDFThe dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and/or solute carrier family 7 member 11 (SLC7A11) is believed to contribute to ferroptosis in the hearts suffered ischemia/reperfusion (I/R), but the mechanisms behind the dysregulation of them are not fully elucidated. Mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) can function as a paracaspase to cleave specified substrates and it is predicted to interact with Nrf2. This study aims to explore whether targeting MALT1 can reduce I/R-induced ferroptosis via enhancing the Nrf2/SLC7A11 pathway.
View Article and Find Full Text PDFMetal homeostasis is critical to normal neurophysiological activity. Metal ions are involved in the development, metabolism, redox and neurotransmitter transmission of the central nervous system (CNS). Thus, disturbance of homeostasis (such as metal deficiency or excess) can result in serious consequences, including neurooxidative stress, excitotoxicity, neuroinflammation, and nerve cell death.
View Article and Find Full Text PDFInflammopharmacology
April 2023
Neurological symptoms are prevalent in both the acute and post-acute phases of coronavirus disease 2019 (COVID-19), and they are becoming a major concern for the prognosis of COVID-19 patients. Accumulation evidence has suggested that metal ion disorders occur in the central nervous system (CNS) of COVID-19 patients. Metal ions participate in the development, metabolism, redox and neurotransmitter transmission in the CNS and are tightly regulated by metal ion channels.
View Article and Find Full Text PDFArch Biochem Biophys
February 2023
Necroptosis has been demonstrated to contribute to brain injury in ischemic stroke, whereas A20 can exert anti-necroptosis effect via deubiquitinating receptor-interacting protein kinase (RIPK3) at k63 and it can be cleaved by MALT1. This study aims to explore whether MALT1 is upregulated in the brain during ischemic stroke and promotes brain cell necroptosis through enhancing the degradation of A20. Ischemic stroke model was established in Sprague Dawley rats by occlusion of the middle cerebral artery (MCA) for 2 h, followed by 24 h reperfusion, which showed brain injury (increase in neurological deficit score and infarct volume) concomitant with an upregulation of MALT1, a decrease in A20 level, and increases in necroptosis-associated protein levels [RIPK3, mixed lineage kinase domain-like protein (MLKL) and p-MLKL] and k63-ubiquitination of RIPK3 in brain tissues.
View Article and Find Full Text PDFGlutamate receptor ionotropic NMDA 2B (GluN2B) plays an essential role in calcium overload during excitotoxicity. Reverse-phase nano-liquid chromatography-tandem mass spectrometry has revealed an interaction between GluN2B and HECT domain E3 ubiquitin protein ligase 4 (HECTD4), an E3 ubiquitin ligase highly expressed in the brain. As a potential substrate for HECTD4, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) acts as a scaffold with hydrolysis activity.
View Article and Find Full Text PDFFerroptosis is an iron-dependent cell death and contributes to doxorubicin-induced cardiotoxicity, but the mechanisms behind intracellular iron overload in cardiomyocyte after administration of doxorubicin remain largely unknown. Ferritinophagy is a selective type of autophagy and could be a novel source for intracellular free iron. Spermatogenesis-associated protein 2 (SPATA2), a member of the TNF signaling pathway, can recruit cylindromatosis (CYLD, a deubiquitinating enzyme) to regulate cell death.
View Article and Find Full Text PDFAims: Vascular peroxidase 1 (VPO1) plays an important role in mediation of vascular remodeling with pulmonary arterial hypertension (PAH). This study aims to determine whether VPO1 can promote phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanisms.
Main Methods: Sprague-Dawley (SD) rats were exposed to 10 % O for 21 days to establish the model of vascular remodeling in pulmonary arterial hypertension.
Right ventricular (RV) remodeling is a major feature of pulmonary arterial hypertension (PAH). Vascular peroxidase 1 (VPO1) is reported to participate in the process of PAH. This study aims to explore whether VPO1 contributes to hypoxia-induced cardiac hypertrophy and the underlying mechanisms.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
December 2022
Background: Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression.
Objective: The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression.
Methods: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b.
Endosomal sorting complex required for transport III (ESCRT-III) machinery is a key component to counteract the mixed lineage kinase domain-like pseudokinase (MLKL)-induced plasma membrane broken in cells undergoing necroptosis. Based on the bioinformatics analysis, polymyxin B, a polypeptide antibiotic, is predicted to simultaneously interact with ESCRT-III subunits and necroptosis-relevant proteins. This study aims to explore whether polymyxin B could reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and/or suppressing the RIPK1/RIPK3/MLKL pathway.
View Article and Find Full Text PDFBiochem Pharmacol
April 2022
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a multifunctional protein. MALT1 functions as an adaptor protein to assemble and recruit proteins such as B-cell lymphoma 10 (BCL10) and caspase-recruitment domain (CARD)-containing coiled-coil protein 11 (CARD11). Conversely it also acts as a paracaspase to cleave specified substrates.
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