CIRCUSP42 AMELIORATES LPS-INDUCED HUMAN RENAL EPITHELIAL CELLS IN VITRO BY REGULATING THE MIR-182-5P/DUSP1 AXIS.

Background: Sepsis is a life-threatening systemic inflammatory disease that can cause many diseases, including acute kidney injury (AKI). Increasing evidence showed that a variety of circular RNAs were considered to be involved in the development of the disease. In this study, we aimed to elucidate the role and potential mechanism of circUSP42 in sepsis-induced AKI.

Mechanism of fibroblast growth factor 21 in cardiac remodeling.

Cardiac remodeling is a basic pathological process that enables the progression of multiple cardiac diseases to heart failure. Fibroblast growth factor 21 is considered a regulator in maintaining energy homeostasis and shows a positive role in preventing damage caused by cardiac diseases. This review mainly summarizes the effects and related mechanisms of fibroblast growth factor 21 on pathological processes associated with cardiac remodeling, based on a variety of cells of myocardial tissue.

VDAC1 promotes cardiomyocyte autophagy in anoxia/reoxygenation injury via the PINK1/Parkin pathway.

Ischemia/reperfusion (I/R) is a well-known injury to the myocardium, but the mechanism involved remains elusive. In addition to the well-accepted apoptosis theory, autophagy was recently found to be involved in the process, exerting a dual role as protection in ischemia and detriment in reperfusion. Activation of autophagy is mediated by mitochondrial permeability transition pore (MPTP) opening during reperfusion.

Downregulation of TSPO expression inhibits oxidative stress and maintains mitochondrial homeostasis in cardiomyocytes subjected to anoxia/reoxygenation injury.

Translocator protein (TSPO) is highly expressed in the cardiovascular system, exerting crucial effects on both myocardial damage and protection. However, the role and mechanism of TSPO in myocardial ischemia/reperfusion (I/R) injury remains elusive. In the current study, we subjected H9c2 cardiomyocytes to anoxia/reoxygenation (A/R) and knocked down TSPO expression by RNA interference to investigate the possible mechanism of TSPO on I/R injury.

Resveratrol protects cardiomyocytes against anoxia/reoxygenation via dephosphorylation of VDAC1 by Akt-GSK3 β pathway.

Our previous studies showed that the effect of resveratrol preventing mitochondrial permeability transition pore (mPTP) opening in myocardial ischemia/reperfusion injury was achieved by regulating voltage-dependent anion channel 1 (VDAC1). However, the underlying mechanism remains unclear. Previous studies demonstrated that the activity and function of VDAC1 are highly regulated by post-translational modification.

Dual action of vitamin C in iron supplement therapeutics for iron deficiency anemia: prevention of liver damage induced by iron overload.

Vitamin C, an excellent reducing agent, aids in increasing absorbable ferrous iron in iron deficiency anemia. As an efficient antioxidant, it is still unknown whether vitamin C exerts protective effects against liver damage caused by iron excess and whether mitochondria are the target effectors of the above effects. In this study, 48 mice were randomly divided into a control group, iron-overload group, TAU-treated + iron-overload group and vitamin C-treated + iron-overload group with 12 mice per group.

Capsaicin Protects Cardiomyocytes against Anoxia/Reoxygenation Injury via Preventing Mitochondrial Dysfunction Mediated by SIRT1.

Capsaicin (Cap) has been reported to have beneficial effects on cardiovascular system, but the mechanisms underlying these effects are still poorly understood. Apoptosis has been shown to be involved in mitochondrial dysfunction, and upregulating expression of SIRT1 can inhibit the apoptosis of cardiomyocytes induced by anoxia/reoxygenation (A/R). Therefore, the aim of this study was to test whether the protective effects of Cap against the injury to the cardiomyocytes are mediated by SIRT1.

VDAC1 deacetylation is involved in the protective effects of resveratrol against mitochondria-mediated apoptosis in cardiomyocytes subjected to anoxia/reoxygenation injury.

We have recently demonstrated that Voltage-dependent anion channel 1 (VDAC1), a protein located in the mitochondrial outer membrane, is involved in the effects of resveratrol on the mitochondrial permeability transition pore (mPTP). However, the underlying mechanism of action remains to be elucidated. In the present study, we demonstrated that resveratrol promoted VDAC1 deacetylation in cardiomyocytes in response to anoxia/reoxygenation (A/R) injury.

Sasanquasaponin induces increase of Cl‑/HCO3‑ exchange of anion exchanger 3 and promotes intracellular Cl‑ efflux in hypoxia/reoxygenation cardiomyocytes.

Anion exchanger 3 (AE3) is known to serve crucial roles in maintaining intracellular chloride homeostasis by facilitating the reversible electroneutral exchange of Cl‑ for HCO3‑ across the plasma membrane. Our previous studies reported that sasanquasaponin (SQS) can inhibit hypoxia/reoxygenation (H/R)‑induced elevation of intracellular Cl‑ concentration ([Cl‑]i) and elicit cardioprotection by favoring Cl‑/HCO3‑ exchange of AE3. However, the molecular basis for SQS‑induced increase of Cl‑/HCO3‑ exchange of AE3 remains unclear.

Neutrophil Elastase Regulates Emergency Myelopoiesis Preceding Systemic Inflammation in Diet-induced Obesity.

Inflammation plays a significant role in the development of obesity-related complications, but the molecular events that initiate and propagate such inflammation remain unclear. Here, we report that mice fed a high-fat diet (HFD) for as little as 1-3 days show increased differentiation of myeloid progenitors into neutrophils and monocytes but reduced B lymphocyte production in the bone marrow. Levels of neutrophil elastase (NE) and the nuclear factors CCAAT/enhancer-binding protein α (C/EBPα) and growth factor-independent 1 (GFI-1) are elevated in hematopoietic stem and progenitor cells from HFD-fed mice, but mice lacking either NE or C/EBPα are resistant to HFD-induced myelopoiesis.

Involvement of DJ‑1 in ischemic preconditioning‑induced delayed cardioprotection in vivo.

DJ‑1 protein, as a multifunctional intracellular protein, has been demonstrated to serve a critical role in regulating cell survival and oxidative stress. To provide in vivo evidence that DJ‑1 is involved in the delayed cardioprotection induced by ischemic preconditioning (IPC) against oxidative stress caused by ischemia/reperfusion (I/R), the present study subjected male Sprague‑Dawley rats to IPC (3 cycles of 5‑min coronary occlusion/5‑min reperfusion) 24 h prior to I/R (30‑min coronary occlusion/120‑min reperfusion). A lentiviral vector containing short hairpin RNA was injected into the left ventricle three weeks prior to IPC, to knockdown DJ‑1 in situ.

Sasanquasaponin-induced cardioprotection involves inhibition of mPTP opening via attenuating intracellular chloride accumulation.

Sasanquasaponin (SQS) has been reported to elicit cardioprotection by suppressing hypoxia/reoxygenation (H/R)-induced elevation of intracellular chloride ion concentration ([Cl]). Given that the increased [Cl] is involved to modulate the mitochondrial permeability transition pore (mPTP), we herein sought to further investigate the role of mPTP in the cardioprotective effect of SQS on H/R injury. H9c2 cells were incubated for 24h with or without 10μM SQS followed by H/R.

Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading.

Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU).

Sasanquasaponin promotes cellular chloride efflux and elicits cardioprotection via the PKCε pathway.

Sasanquasaponin (SQS) is an active component of Camellia oleifera Abel. A recent study by our group demonstrated that SQS was able to inhibit ischemia/reperfusion‑induced elevation of the intracellular chloride ion concentration ([Cl‑]i) and exerted cardioprotective effects; however, the underlying intracellular signal transduction mechanisms have yet to be elucidated. As protein kinase C ε (PKCε) is able to mediate Cl‑ homeostasis, the present study investigated its possible involvement in the effects of SQS on cardiomyocytes subjected to ischemia/reperfusion injury.

Kaempferol protects cardiomyocytes against anoxia/reoxygenation injury via mitochondrial pathway mediated by SIRT1.

Mitochondria-mediated apoptosis is a critical mechanism of anoxia/ reoxygenation (A/R)-induced injury in cardiomyocytes. Kaempferol (Kae) is a natural polyphenol and a type of flavonoid, which has been demonstrated to protect myocardium against ischemia/reperfusion (I/R) injury. However, the mechanism is still not fully elucidated.

DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway.

DJ-1 protein, as a multifunctional intracellular protein, has an important role in transcriptional regulation and anti-oxidant stress. A recent study by our group showed that DJ-1 can regulate the expression of certain anti‑oxidant enzymes and attenuate hypoxia/re‑oxygenation (H/R)‑induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2‑like 2 (Nrf2) is an essential transcription factor that regulates the expression of several anti‑oxidant genes via binding to the anti‑oxidant response element (ARE).

DJ-1 Mediates the Delayed Cardioprotection of Hypoxic Preconditioning Through Activation of Nrf2 and Subsequent Upregulation of Antioxidative Enzymes.

We have recently shown that DJ-1 is implicated in the delayed cardioprotective effect of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R) injury as an endogenous protective protein. This study aims to further investigate the underlying mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress. Using a well-characterized cellular model of HPC from rat heart-derived H9c2 cells, we found that HPC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein-1 (Keap1) dissociation and resulted in increased nuclear translocation, antioxidant response element-binding, and transcriptional activity of Nrf2 24 hours after HPC, with subsequent upregulation of manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1), which provided delayed protection against H/R-induced oxidative stress in normal H9c2 cells.

Long-term oral resveratrol intake provides nutritional preconditioning against myocardial ischemia/reperfusion injury: involvement of VDAC1 downregulation.

Scope: This study elucidates the effects of long-term nutritional preconditioning by resveratrol on ischemia/reperfusion (I/R) injury and its underlying mechanisms.

Methods And Results: Mice were treated with resveratrol at 2.0 mg/kg/day by gastric gavages for 6 wk.

Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model.

We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production.

14-3-3γ protein attenuates lipopolysaccharide-induced cardiomyocytes injury through the Bcl-2 family/mitochondria pathway.

Previous studies have indicated that 14-3-3γ is upregulated by stress in LPS-induced cardiovascular injury. In this study, we investigated the interaction of 14-3-3γ and Bcl-2 family members in the control of the mitochondrial permeability transition (MPT) to test the hypothesis that abundant levels of 14-3-3γ can protect against LPS-induced injury via a Bcl-2 family/mitochondria pathway. The cardiomyocytes were treated with LPS (1mg l(-1)) for 6h; the interaction between 14-3-3γ and phospho-Bad(S112) was detected by co-immunoprecipitation (co-IP); the levels of Bcl-2 family members in the cytosolic and mitochondrial fractions were examined by Western blot; the apoptosis and mitochondrial membrane potential (ΔΨm) were detected by flow cytometry; and the mitochondrial permeability transition pore (mPTP) opening was tested by mitochondrial swelling.

Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for hypoxic preconditioning-mediated delayed cardioprotection.

It has been well demonstrated that hypoxic preconditioning (HPC) can attenuate hypoxia/reoxygenation (H/R)-induced oxidant stress and elicit delayed cardioprotection by upregulating the expression of multiple antioxidative enzymes such as heme oxygenase-1 (HO-1), manganese superoxide dismutase (MnSOD) and so on. However, the underlying mechanisms of HPC-induced upregulation of antioxidative enzymes are not fully understood. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that regulates expression of several antioxidant genes via binding to the antioxidant response element (ARE) and plays a crucial role in cellular defence against oxidative stress.

Mechanism of chronic dietary iron overload-induced liver damage in mice.

Chronic iron overload may result in hepatic fibrosis and even neoplastic transformation due to a burst of reactive oxygen species (ROS). Mitochondria have been proposed to be important in the production of ROS. The purpose of this study was to investigate the role of the mitochondrial permeability transition pore (mPTP) in the burst of ROS, and to clarify the mechanism whereby ROS induced by iron overload results in hepatic damage.

The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs.

Aim: To investigate the protective effects of preconditioning human umbilical vein endothelial cells (HUVECs) with Polygonum multiflorum stilbeneglycoside (PMS) under anoxia/reoxygenation (A/R), and the mechanism of protection.

Methods: Prior to A/R, HUVECs were incubated with PMS (0.6 x 10(-11), 1.

Cardioprotective effect of sasanquasaponin preconditioning via bradykinin-NO pathway in isolated rat heart.

Sasanquasaponin (SQS) is an effective component of Camellia oleifera Abel. This study was designed to investigate the cardioprotective effect of SQS against ischemia-reperfusion (I/R) injury and the possible mechanism in isolated rat hearts. These hearts were pretreated by SQS only or SQS and HOE140 in different groups, and then subjected to I/R injury.