AMPK: The key to ischemia‐reperfusion injury Cai, Jie; Chen, Xinyue; Liu, Xingyu ...
Journal of cellular physiology,
November 2022, 2022-11-00, 20221101, Letnik:
237, Številka:
11
Journal Article
Recenzirano
Ischemia‐reperfusion injury (IRI) refers to a syndrome in which tissue damage is further aggravated and organ function further deteriorates when blood flow is restored after a period of tissue ...ischemia. Acute myocardial infarction, stress ulcer, pancreatitis, intestinal ischemia, intermittent claudication, acute tubular necrosis, postshock liver failure, and multisystem organ failure are all related to reperfusion injury. AMP‐activated protein kinase (AMPK) has been identified in multiple catabolic and anabolic signaling pathways. The functions of AMPK during health and diseases are intriguing but still need further research. Except for its conventional roles as an intracellular energy switch, emerging evidence reveals the critical role of AMPK in IRI as an energy‐sensing signal molecule by regulating metabolism, autophagy, oxidative stress, inflammation, and other progressions. At the same time, drugs based on AMPK for the treatment of IRI are constantly being researched and applied in clinics. In this review, we summarize the mechanisms underlying the effects of AMPK in IRI and describe the AMPK‐targeting drugs in treatment, hoping to increase the understanding of AMPK in IRI and provide new insights into future clinical treatment.
With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further ...explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications.
we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects.
In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.
Based on the concept of the preformed failure plane, this paper conducted a series of clay-interface tests using a modified triaxial apparatus that can directly measure the interface pore pressure, ...to investigate the shear rate and interface roughness effect on the deviator stress, interface excess pore pressure, interface stress path, and interface friction angle in both consolidated undrained (CU) and consolidated partially drained (CPD) interface drainage conditions. In general, the specimen with the clay-steel interface had a lower shear strength than the pure clay specimen under the same testing conditions. In CU tests, the total and effective interface friction angles increase approximately linearly with the shear rate in the semi-logarithmic scale, while in CPD tests, both the total and effective interface friction angles decrease with increasing shear rate. Moreover, the increased surface roughness is found to enhance the interface shear strength and the maximum interface pore pressure at a given shear rate and confining pressure. In CU tests, both the normalized efficiency parameter E and the corresponding interface friction angle increase with the average roughness (Ra) in a logarithmic relationship, but it is difficult to describe the positive correlation perfectly in CPD tests.
•The triaxial apparatus has been modified to study the mechanical properties of the clay-steel structure interface.•The pore pressure at the clay-structure interface has been measured directly and fully investigated.•Two interface drainage conditions have been considered: consolidated undrained (CU) and consolidated partially drained (CPD).•The roughness effect and shear rate effect on the clay-steel structure interface were evaluated.
Herein, we report a visible light-enabled radical trihalomethylation/cyano-migration/carbonylation cascade reaction of 2-hydroxy-2-hex-5-enenitrile with CX3SO2Cl as the CX3-source (X = F, Cl) to ...obtain 5-oxo-2-(2,2,2-trihaloethyl)pentanenitrile compounds in the absence of a photocatalyst, transition metal and base. This reaction system is also effective to convert (benzodthiazol-2-yl)-pent-4-enol to the corresponding 4-(benzodthiazol-2-yl)-6,6,6-trihalo-hexanone products. These reactions occur under mild conditions, tolerate a wide range of functional groups, and provide alternative approaches for the 1,2-bifunctionalization reaction of unactivated olefins.
•Focus on clay-suction caisson interface undrained properties.•Investigating the overconsolidation ratios effect on interface undrained strength.•Evaluating the shear rate effect on interface ...undrained strength.•Evaluating the shear rate effect on internal and interface friction angles.
The interface resistance during installation is crucial for the stability and safety of suction caisson in offshore geotechnical engineering, which is strongly affected by the penetration rate and soil–structure interface mechanical properties. This research conducts a series of clay–structure interface shear tests using modified direct simple shear device to fully study the mechanical behavior of clay–suction caisson interface. The effect of shear rate, over consolidation ratios (OCRs), interface boundary conditions, stress levels, and interface roughness were considered. Results show that as the OCR increases, the strength of both the clay and interface increase but show distinct patterns under constant volume (CV) and constant normal load (CNL) boundary condition. It was found that the interface strength is positively related to interface roughness and shear rate impact both the clay and corresponding interface strength. Under CNL conditions, the strength of normally consolidated (NC) clay decreases with rising shear rate, while the over consolidated (OC) clay demonstrate a opposite trend. In contrast, the effect of shear rate on interface behavior gets complicated owing to the combination of roughness, stress levels, and OCRs. Under CV conditions, the shear strength of clay and interface exhibits a logarithmic growth relationship with shear rates. The result of this work can provide a basis for interface resistance evaluation for suction caisson installation in clay.
A method has been developed for the simultaneous determination of 23 antibiotics (four categories) and 3 β-agonists in livestock drinking water using solid-phase extraction and ultra performance ...liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS). The samples were adjusted pH to 5. 0, added Na2EDTA, enriched and cleaned-up by an HLB solid-phase extraction cartridge. The target compounds were confirmed and quantified by UPLC-ESI MS/MS with external standard method for the anti- biotics and internal standard method for the β-agonists. The recoveries were assessed by using lab tap water as matrix. The average recoveries of the 23 antibiotics and the 3 β-agonists were in the range of 50. 7%-104. 6% and the relative standard deviations (RSDs) were 2. 6%-8. 8% (n= 3). Under the optimal conditions, the calibration curves of the 23 antibiotics and the 3 β-agonists showed good linearity with the correlation coefficients better than 0. 994. The limits of detection (LODs,
Copper is a vital mineral, and an optimal amount of copper is required to support normal physiologic processes in various systems, including the cardiovascular system. Over the past few decades, ...copper-induced cell death, named cuproptosis, has become increasingly recognized as an important process mediating the pathogenesis and progression of cardiovascular disease (CVD), including atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. Therefore, an in-depth understanding of the regulatory mechanisms of cuproptosis in CVD may be useful for improving CVD management. Here, we review the relationship between copper homeostasis and cuproptosis-related pathways in CVD, as well as therapeutic strategies addressing copper-induced cell death in CVD.
With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor ...enriched exosome from finbrin gel was a promising strategy to promote wound healing.
To address this unsolved problem, we developed clinical-grade platelets exosome product (PEP), which was incorporate with injectable surgical fibrin sealant (TISSEEL), to promote chronic wound healing and complete skin regeneration. The PEP characterization stimulated cellular activities and
rabbit ischemic wound healing capacity of TISSEEL-PEP were performed and analyzed.
PEP, enriched with transforming growth factor beta (TGF-β), possessed exosomal characteristics including exosome size, morphology, and typical markers including CD63, CD9, and ALG-2-interacting protein X (Alix).
, PEP significantly promoted cell proliferation, migration, tube formation, as well as skin organoid formation. Topical treatment of ischemic wounds with TISSEEL-PEP promoted full-thickness healing with the reacquisition of hair follicles and sebaceous glands. Superior to untreated and TISSEEL-only treated controls, TISSEEL-PEP drove cutaneous healing associated with collagen synthesis and restoration of dermal architecture. Furthermore, PEP promoted epithelial and vascular cell activity enhancing angiogenesis to restore blood flow and mature skin function. Transcriptome deconvolution of TISSEEL-PEP versus TISSEEL-only treated wounds prioritized regenerative pathways encompassing neovascularization, matrix remodeling and tissue growth.
This room-temperature stable, lyophilized exosome product is thus capable of delivering a bioactive transforming growth factor beta to drive regenerative events.
Chinese mitten crab (Eriocheir sinensis) as a commercially important species is widely cultured in China. However, E. sinensis is prone to agonistic behavior, which causes physical damage and wastes ...energy resources, negatively impacting their growth and survival. Therefore, understanding the regulatory mechanisms that underlie the switching of such behavior is essential for ensuring the efficient and cost-effective aquaculture of E. sinensis. The 5-HT2B receptor is a key downstream target of serotonin (5-HT), which is involved in regulating animal behavior. In this study, the full-length sequence of 5-HT2B gene was cloned. The total length of the 5-HT2B gene was found to be 3127 bp with a 236 bp 5'-UTR (untranslated region), a 779 bp 3'-UTR, and a 2112 bp open reading frame encoding 703 amino acids. Phylogenetic tree analysis revealed that the 5-HT2B amino acid sequence of E. sinensis is highly conserved with that of Cancer borealis. Using in vitro co-culture and luciferase assays, the miR-143 targets the 5-HT2B 3'-UTR and inhibits 5-HT2B expression was confirmed. Furthermore, RT-qPCR and Western blotting analyses revealed that the miR-143 mimic significantly inhibits 5-HT2B mRNA and protein expression. However, injection of miR-143 did not decrease agonistic behavior, indicating that 5-HT2B is not involved in the regulation of such behavior in E. sinensis.
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