Electrostatic Charge‐Mediated Apoptotic Vesicle Biodistribution Attenuates Sepsis by Switching Neutrophil NETosis to Apoptosis DOI
Qianmin Ou,

Lingping Tan,

Yi-ting Shao

и другие.

Small, Год журнала: 2022, Номер 18(20)

Опубликована: Апрель 15, 2022

Abstract Mesenchymal stem cell (MSC) therapy can attenuate organ damage and reduce mortality in sepsis; however, the detailed mechanism is not fully elucidated. In this study, it shown that MSC‐derived apoptotic vesicles (apoVs) ameliorate multiple dysfunction improve survival septic mice. Mechanistically, found tail vein‐infused apoVs mainly accumulate bone marrow of mice via electrostatic charge interactions with positively charged neutrophil extracellular traps (NETs). Moreover, switch neutrophils NETosis to apoptosis apoV‐Fas ligand (FasL)‐activated Fas pathway. summary, these findings uncover a previously unknown role sepsis treatment an charge‐directed target therapeutic mechanism, suggesting death associated disease development therapy.

Язык: Английский

DNA-PKcs promotes sepsis-induced multiple organ failure by triggering mitochondrial dysfunction DOI Creative Commons
Rongjun Zou, Jun Tao, Junxiong Qiu

и другие.

Journal of Advanced Research, Год журнала: 2022, Номер 41, С. 39 - 48

Опубликована: Янв. 31, 2022

Multiple organ failure is the commonest cause of death in septic patients. This study was undertaken an attempt to elucidate functional importance DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on mitochondrial dysfunction associated with development and progression sepsis-related multiple syndrome (MODS). Cardiomyocyte-specific DNA-PKcs knockout (DNA-PKcsCKO) mice, liver-specific (DNA-PKcsLKO) kidney tubular cell-specific (DNA-PKcsTKO) mice were used generate LPS-induced sepsis model. Echocardiography, serum biochemistry, tissue microscopy analyze damage morphological changes induced by sepsis. Mitochondrial function dynamics determined qPCR, western blotting, ELISA, mt-Keima immunofluorescence assays following siRNA-mediated DNA-PKCs knockdown cardiomyocytes, hepatocytes, cells. deletion attenuated sepsis-mediated myocardial through improving metabolism. Loss protected liver against inhibition oxidative apoptosis. deficiency sustained upon LPS stress normalization fission/fusion events, mitophagy, biogenesis. We conclude that strategies targeting expression or activity may be valuable therapeutic options prevent reduce sepsis-induced MODS.

Язык: Английский

Процитировано

64
Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia-Reperfusion Injury DOI Creative Commons
Hang Zhu, Hao Zhou

Oxidative Medicine and Cellular Longevity, Год журнала: 2021, Номер 2021(1)

Опубликована: Янв. 1, 2021

Impaired function of the endoplasmic reticulum (ER) is followed by evolutionarily conserved cell stress responses, which are employed cells, including cardiomyocytes, to maintain and/or restore ER homeostasis. activates unfolded protein response (UPR) degrade and remove abnormal proteins from lumen. Although UPR an intracellular defense mechanism sustain cardiomyocyte viability heart function, excessive activation initiates ER‐dependent apoptosis. Myocardial ischemia/reperfusion (I/R) injury a pathological process occurring during or after revascularization ischemic myocardium. Several molecular mechanisms contribute pathogenesis cardiac I/R injury. Due dual protective/degradative effects on it interest understand basic concepts, regulatory signals, processes involved in following myocardial In this review, therefore, we present recent findings related novel components activation. The complex whether they mitigate exacerbate summarized serve as basis for research into potential therapies cardioprotection through control

Язык: Английский

Процитировано

62
Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options DOI Creative Commons
Teresa Salvatore, Raffaele Galiero, Alfredo Caturano

и другие.

Biomedicines, Год журнала: 2022, Номер 10(9), С. 2274 - 2274

Опубликована: Сен. 14, 2022

Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of combination altered vasomotion and long-term structural change to arterioles leading impaired regulation blood flow in response changing cardiomyocyte oxygen requirements. The pathogenesis this complication is complex not completely known, involving several alterations among which hyperglycemia insulin resistance play particularly central roles oxidative stress, inflammatory activation barrier function endothelium. CMD significantly contributes cardiac events such as angina or infarction without obstructive artery disease, well heart failure, especially the phenotype associated with preserved ejection fraction, greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target vascular damage, but recent experimental studies some clinical investigations have produced data favor potential beneficial effects on micro vessels caused two classes glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy inhibitors sodium-glucose cotransporter-2 (SGLT2). purpose review describe pathophysiological mechanisms, manifestations particular reference diabetes, summarize protective antidiabetic drugs myocardial compartment.

Язык: Английский

Процитировано

54
The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways DOI Creative Commons

Wenzhen Xu,

Han Lu, Yuan Yuan

и другие.

Foods, Год журнала: 2022, Номер 11(16), С. 2439 - 2439

Опубликована: Авг. 13, 2022

Accumulating evidence shows that oxidative stress and inflammation contribute to the development of cardiovascular disease. It has been suggested propolis possesses antioxidant anti-inflammatory activities. In this study, effects main flavonoids (chrysin, pinocembrin, galangin, pinobanksin) extract were researched. The results showed cellular ROS (Reactive oxygen species) levels, enzymes, Nrf2 (Nuclear factor erythroid 2-related 2) nuclear translocation, expression NQO1 (NAD(P)H:quinone oxidoreductase 1) HO-1 (heme oxygenase regulated by different concentrations individual extract, which good pro-oxidant effects. For example, levels decreased; SOD CAT activities increased; protein was increased chrysin. demonstrated NO (Nitric Oxide), NOS Oxide Synthase), activation NF-κB signaling pathway inhibited in a dose-dependent manner extract. Moreover, revealed phytochemicals presented at lower but stronger higher concentrations. To maintain balance effects, it is possible activate kappa B) pathway.

Язык: Английский

Процитировано

45
Electrostatic Charge‐Mediated Apoptotic Vesicle Biodistribution Attenuates Sepsis by Switching Neutrophil NETosis to Apoptosis DOI
Qianmin Ou,

Lingping Tan,

Yi-ting Shao

и другие.

Small, Год журнала: 2022, Номер 18(20)

Опубликована: Апрель 15, 2022

Abstract Mesenchymal stem cell (MSC) therapy can attenuate organ damage and reduce mortality in sepsis; however, the detailed mechanism is not fully elucidated. In this study, it shown that MSC‐derived apoptotic vesicles (apoVs) ameliorate multiple dysfunction improve survival septic mice. Mechanistically, found tail vein‐infused apoVs mainly accumulate bone marrow of mice via electrostatic charge interactions with positively charged neutrophil extracellular traps (NETs). Moreover, switch neutrophils NETosis to apoptosis apoV‐Fas ligand (FasL)‐activated Fas pathway. summary, these findings uncover a previously unknown role sepsis treatment an charge‐directed target therapeutic mechanism, suggesting death associated disease development therapy.

Язык: Английский

Процитировано

43