Astragaloside IV intervenes multi-regulatory cell death forms against doxorubicin-induced cardiotoxicity by regulating AMPKα2 pathway.

The clinical use of doxorubicin has been severely limited by doxorubicin-induced cardiotoxicity (DIC). Its mechanism is extremely complex and involves reactive oxygen species overgeneration, DNA damage, and aberrant inflammatory activity, which also involves multi-regulatory cell death mechanisms, including apoptosis, autophagy, and pyroptosis. These mechanisms overlap and crosstalk, resulting in the poor intervention of DIC injury.

Salidroside pretreatment alleviates ferroptosis induced by myocardial ischemia/reperfusion through mitochondrial superoxide-dependent AMPKα2 activation.

Background: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Feaccumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood.

Endurance exercise preconditioning alleviates ferroptosis induced by doxorubicin-induced cardiotoxicity through mitochondrial superoxide-dependent AMPKα2 activation.

Doxorubicin-induced cardiotoxicity (DIC) adversely impacts patients' long-term health and quality of life. Its underlying mechanism is complex, involving regulatory cell death mechanisms, such as ferroptosis and autophagy. Moreover, it is a challenge faced by patients undergoing cardiac rehabilitation.

Renoprotective effects of ferulic acid mediated by AMPKα1 against lipopolysaccharide-induced damage.

The kidney is susceptible to lipopolysaccharide (LPS)-induced damage with sepsis, and renal dysfunction is a leading cause of mortality in patients with sepsis. However, the renoprotective effects of ferulic acid (FA) during sepsis and the underlying mechanism remain unclear. This study explored these renoprotective effects using NRK-52E cells and mice with LPS-induced renal damage.

TanshinoneⅡA inhibits excessive autophagy and protects myocardium against ischemia/reperfusion injury via 14-3-3η/Akt/Beclin1 pathway.

Excessive autophagy induced by reperfusion is one of the causes of severe myocardial injury. Tanshinone IIA (TSN) protects the myocardium against ischemia/reperfusion (I/R) injury. The mechanism by which the inhibition of excessive autophagy contributes to the myocardial protection by TSN is unclear.

Luteoloside pretreatment attenuates anoxia-induced damage in cardiomyocytes by regulating autophagy mediated by 14-3-3η and the AMPKα-mTOR/ULK1 pathway.

The relation between ischemia and heart failure is well demonstrated, and several studies suggested that realizing the physiological role of autophagy will be of great importance. Luteoloside (Lut) is one of the main components of Lonicera japonica flos and exhibits antioxidant, anti-inflammatory, and cardioprotective properties. To determine if Lut pretreatment enhanced autophagy by 14-3-3η expression and the AMPKα-mTOR/ULK1 pathway and protected the neonatal rat cardiomyocytes (NRCMs) against anoxia damage, NRCMs were treated using 20 μM Lut for 36 h, and the anoxia damage model was established using NRCMs.

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPK1 Expression.

Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5' adenosine monophosphate-activated protein kinase 1 (AMPK1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed.

Puerarin activates adaptive autophagy and protects the myocardium against doxorubicin-induced cardiotoxicity via the 14-3-3γ/PKCε pathway.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) seriously threatens the health of related patients. Studies have confirmed that 14-3-3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is a bioactive ingredient isolated from the root of Pueraria lobata.

Taurine Ameliorates Iron Overload-Induced Hepatocyte Injury via the Bcl-2/VDAC1-Mediated Mitochondrial Apoptosis Pathway.

Iron overload can induce reactive oxygen species (ROS) burst and liver damage. Taurine can reduce ROS production and ameliorate liver injury caused by iron overload; however, the underlying molecular mechanism remains elusive. Herein, L02 cells treated with 120 M iron dextran for 48 h showed marked oxidative stress damage and significantly increased apoptosis.

Puerarin attenuates lipopolysaccharide-induced myocardial injury via the 14-3-3γ/PKCε pathway activating adaptive autophagy.

Studies have confirmed that the heart is the main target organ of lipopolysaccharide (LPS) attacks, and 14-3-3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is the major bioactive ingredient isolated from the root of Pueraria lobata. It possesses many pharmacological properties, which has been widely used in the treatment and adjuvant therapy of cardio- and cerebrovascular diseases and cancer, etc.

Ferulic acid protects renal tubular epithelial cells against anoxia/reoxygenation injury mediated by AMPKα1.

Anoxia/reoxygenation (A/R) injury causes dysfunction of rat renal tubular epithelial cells (NRK-52E), which is associated with excess reactive oxygen species (ROS) generation and eventually leads to apoptosis. Ferulic acid (FA), a phenolic acid, which is abundant in fruits and vegetables. FA possesses the properties of scavenging free radicals and cytoprotection against oxygen stress.

Poncirin ameliorates cardiac ischemia-reperfusion injury by activating PI3K/AKT/PGC-1α signaling.

Poncirin, a flavonoid glycoside derivative extracted from the fruits of Poncirus trifoliata (trifoliate orange or Chinese bitter orange), has a variety of documented bioactivities, including anti-tumor, anti-inflammatory, and antioxidant effects. Oxidative stress is a major underlying factor in the pathogenesis of cardiac ischemia-reperfusion (I/R) injury. Therefore, we investigated the protective efficacy of poncirin on primary cardiomyocytes subjected to anoxia-reoxygenation (A/R) injury in vitro, and on rat hearts subjected to ischemia-reperfusion (I/R) injury in vivo.

Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy.

Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets.

Vinegar/Tetramethylpyrazine Induces Nutritional Preconditioning Protecting the Myocardium Mediated by VDAC1.

Vinegar is good for health. Tetramethylpyrazine (TMP) is the main component of its flavor, quality, and function. We hypothesized that vinegar/TMP pretreatment could induce myocardial protection of "nutritional preconditioning (NPC)" by low-dose, long-term supplementation and alleviate the myocardial injury caused by anoxia/reoxygenation (A/R).

Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation.

The myocardium is susceptible to lipopolysaccharide (LPS)-induced damage in sepsis, and cardiac dysfunction is a leading cause of mortality in patients with sepsis. The changes in cardiomyocyte autophagy in sepsis and the effects and mechanism of action of capsaicin (Cap) remain unclear. The potential pathway of 14-3-3γ-dependent autophagy and the effects and mechanisms of Cap were studied in LPS-induced injury to primary cultured neonatal rat cardiomyocytes.

Silencing of the ARK5 gene reverses the drug resistance of multidrug-resistant SGC7901/DDP gastric cancer cells.

For several years, the multidrug resistance (MDR) of gastric cancer cells has been a thorny issue worldwide regarding the chemotherapy process and needs to be solved. Here, we report that the ARK5 gene could promote the multidrug resistance of gastric cancer cells in vitro and in vivo. In this study, LV-ARK5-RNAi lentivirus was used to transfect the parental cell line SGC7901 and MDR cell line SGC7901/DDP to construct a stable model of ARK5 interference.

Capsaicin Alleviates the Deteriorative Mitochondrial Function by Upregulating 14-3-3 in Anoxic or Anoxic/Reoxygenated Cardiomyocytes.

Reactive oxygen species (ROS) are byproducts of a defective electron transport chain (ETC). The redox couples, GSH/GSSG and NAD/NADH, play an essential role in physiology as internal defenses against excessive ROS generation by facilitating intracellular/mitochondrial (mt) redox homeostasis. Anoxia alone and anoxia/reoxygenation (A/R) are dissimilar pathological processes.

Kaempferol protects mitochondria and alleviates damages against endotheliotoxicity induced by doxorubicin.

Kaempferol (Kae), a flavonoid, has been found in fruits and other vegetables, possesses many biological activities. 14-3-3 protein exerts protection on various types of injured tissues and cells. Doxorubicin (Dox) causes excessive reactive oxygen species (ROS) generation, which induces endotheliotoxicity and cardiotoxicity.

Tetramethylpyrazine alleviates iron overload damage in vascular endothelium via upregulating DDAHII expression.

Iron overload causes vascular endothelium damage. It has been thought to relate excessive reactive oxygen species (ROS) generation. Tetramethylpyrazine (TMP), an active ingredient of Ligusticum chuanxiong Hort, protects various cells by inhibiting oxidative stress and cascade reaction of apoptosis.

Nobiletin Regulates ROS/ADMA/DDAHII/eNOS/NO Pathway and Alleviates Vascular Endothelium Injury by Iron Overload.

Iron overload is harmful to health and associates with intracellular excessive reactive oxygen species (ROS) generation. Nobiletin (Nob) is known to be antioxidant and anti-inflammatory. However, whether Nob can protect endothelial cells against iron overload has not been studied, and the specific mechanism has not yet been elucidated.

Doxorubicin Induces Endotheliotoxicity and Mitochondrial Dysfunction ROS/eNOS/NO Pathway.

Doxorubicin (Dox) can induce endotheliotoxicity and damage the vascular endothelium (VE). The most principle mechanism might be excess reactive oxygen species (ROS) generation. Nevertheless, the characteristics of ROS generation, downstream mechanisms, and target organelles in Dox-induced endotheliotoxicity have yet to be elucidated.

Tetramethylpyrazine Attenuates the Endotheliotoxicity and the Mitochondrial Dysfunction by Doxorubicin 14-3-3/Bcl-2.

Doxorubicin (Dox) with cardiotoxicity and endotheliotoxicity limits its clinical application for cancer. The toxicitic mechanism involves excess ROS generation. 14-3-3s have the protective effects on various injured tissues and cells.

Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway.

The aberrant accumulation of iron causes vascular endothelium damage, which is thought to be associated with excess reactive oxygen species (ROS) generation. Quercetin (Que), as a flavonoid, has a certain ability to scavenge free radicals. Therefore, we aimed to explore the protective mechanism of Que on iron overload induced HUVECs injury focused on ROS/ADMA/DDAHⅡ/eNOS/NO pathway.

Metabolomics study of serum and urine samples reveals metabolic pathways and biomarkers associated with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common medical condition among women and involves complicated diagnostics and controversial surgical management. The exact molecular mechanism underlying POP is poorly understood, especially at the metabolism level. To explore the metabolic mechanism underlying POP and discover potential biomarkers for POP diagnosis, we applied a non-targeted metabolomics approach using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS).

Iron Overload Damages the Endothelial Mitochondria the ROS/ADMA/DDAHII/eNOS/NO Pathway.

It has been recognized that iron overload may harm the body's health. Vascular endothelial cells (VECs) are one of the main targets of iron overload injury, and the mechanism involved was thought to be related to the excessive generation of reactive oxygen species (ROS). However, the subcellular and temporal characteristics of ROS generation, potential downstream mechanisms, and target organelles in VECs injured by iron overload have not been expounded yet.