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Ischemia‐reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase‐3β (GSK‐3β) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK‐3β provides protection against IRI, making it a viable target for drug development. Though numerous GSK‐3β inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK‐3β roles in IRI. First, we provide an overview of GSK‐3β's basic background. Subsequently, we briefly review the pathological mechanisms of GSK‐3β in accelerating IRI, and highlight the latest progress of GSK‐3β in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK‐3β inhibitors in various organ IRI, offering a thorough and insightful reference for GSK‐3β as a potential target for future IRI therapy. [ABSTRACT FROM AUTHOR]

Pterostilbene (PTE, trans‐3,5‐dimethoxy‐4′‐hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2O2)‐induced oxidative stress HL‐1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real‐time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2O2‐injured HL‐1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE‐mediated pleiotropic effects. Significance statement: Oxidative stress causes detrimental effects on cellular components, further promoting the generation of free radicals and intracellular oxidative stress. Pterostilbene (PTE) is a natural plant polyphenol, and has a variety of pharmacological effects. In this study, we proved in vitro evidence of the cardioprotective effects of PTE against oxidative stress injury, primarily through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Furthermore, GAS6/Axl axis is the surprisingly prominent in the PTE‐mediated pleiotropic effects. [ABSTRACT FROM AUTHOR]

Cerebral injury is closely associated with enhanced oxidative stress. A newly discovered secretory adipocytokine, intelectin‐1 (ITLN‐1), has been shown to have beneficial effects in neuroprotection in epidemiological studies. However, the specific molecular mechanism of ITLN‐1 in protecting against cerebral oxidative stress needs further investigation. In this study, we hypothesize that ITLN‐1 plays a protective role against oxidative stress injury through the SIRT1/PGC1‐α signaling pathway in neuromatocytes. We used hydrogen peroxide (H2O2) as a oxidative stress model to simulate oxidative stress injury. Then, small interfering RNAs (siRNAs) was used to knock down SIRT1 in N2a cells with or without ITLN overexpression, followed by H2O2‐induced injury. We observed that H2O2 injury significantly decreased the levels of ITLN‐1, SIRT1, and PGC‐1α. However, ITLN overexpression reversed H2O2‐induced decline in cell viability and rise in apoptosis and intracellular ROS levels in N2a cells, while ITLN siRNA worsened the neurocyte injury. Furthermore, SIRT1 knockdown reversed the positive effect of ITLN overexpression on oxidative stress injury in N2a cells. Taken together, these findings suggest that ITLN‐1 exerts neuroprotective effects against oxidative stress injury primarily through the SIRT1/PGC‐1α axis. [ABSTRACT FROM AUTHOR]

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti‐inflammatory, anti‐vitiligo, anti‐bacterial, and anti‐viral effects. Growth arrest‐specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor‐related factor 2 (Nrf‐2), NAD(P)H dehydrogenase quinone‐1 (NQO1), heme oxygenase‐1 (HO‐1), silent information regulator 1 (SIRT1), peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B‐cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR‐induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling. [ABSTRACT FROM AUTHOR]

Liver X receptor α (LXRα; also known as NR1H3), an isoform of LXRs, is a member of the nuclear receptor family of transcription factors and plays essential roles in the transcriptional control of cholesterol homeostasis. Previous in‐depth phenotypic analyses of mouse models with deficient LXRα have also demonstrated various physiological functions of this receptor within inflammatory responses. LXRα activation exerts a combination of metabolic and anti‐inflammatory actions resulting in the modulation and the amelioration of inflammatory disorders. The tight "repercussions" between LXRα and inflammation, as well as cholesterol homeostasis, have suggested that LXRα could be pharmacologically targeted in pathologies such as atherosclerosis, acute lung injury, and Alzheimer's disease. This review gives an overview of the recent advances in understanding the roles of LXRα in inflammation and inflammation‐associated diseases, which will help in the design of future experimental researches on the potential of LXRα and advance the investigation of LXRα as pharmacological inflammatory targets. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6), a vitamin K-dependent secretory protein, promotes cell proliferation and inhibits inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors., Objectives: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial IR injury., Methods: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury., Results: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR) injury. GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade., Conclusions: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H 2 O 2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H 2 O 2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects., (© 2024 John Wiley & Sons Ltd.)

Inflammation underlies a wide variety of physiological and pathological processes, and plays a pivotal role in controlling pathogen infection. C1q/tumor necrosis factor (TNF) related proteins (CTRPs), a newly discovered adipokine family with conservative structure and wide distribution, has attracted increasing attention. The CTRP family consists of more than 15 members which fall into the characteristic C1q domain. Increasing studies have demonstrated that CTRPs are involved in the onset and development of inflammation and metabolism as well as related diseases, including myocardial infarction, sepsis and tumors. Here, we first clarified the characteristic domains of CTRPs, and then elucidated their roles in inflammatory-related diseases. Taken together, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.