The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

Zhao, Huijie; Yang, Yihan; Si, Xinya; Liu, Huiyang; Wang, Honggang

doi:10.3390/biom12071010

Cited by 20 publications

(8 citation statements)

References 102 publications

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“…B355252 suppressed TLR4, NLRP3, caspase-1, IL-1β, and IL-18 in LPS-injected animals, demonstrating that B355252 is capable of inhibiting the LPS-activated pyroptosis signaling pathway. Pyroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, metabolic diseases, and neurological diseases (for reviews, see [42][43][44][45][46][47][48]). In the nervous system, pyroptosis is associated with Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and cerebral stroke.…”

Section: Discussionmentioning

confidence: 99%

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

He,

Qi,

Ibeanu

et al. 2024

Brain Sciences

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B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1β, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

He,

Qi,

Ibeanu

et al. 2024

Brain Sciences

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“…Normally, autophagy is related to apoptosis as well as the mechanism of cell death. 28 , 29 There is a complex cross-regulation between autophagy and apoptosis, involving a variety of common regulatory factors and signal transduction pathways. 30 The initiation of autophagy protects cells from apoptosis in IVDD, highlighting its major cytoprotective role.…”

Section: Autophagy Biologymentioning

confidence: 99%

Role of Autophagy and Pyroptosis in Intervertebral Disc Degeneration

Wang,

Li,

et al. 2024

JIR

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Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.

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“…Some studies indicated that MSCs could attenuate the ischemia-reperfusion injury (IRI), which is a common complication of LT serving as a key limiting factor for a good outcome in the patients. Some studies revealed that MSCs could modulate oxidative stress, autophagy, and apoptosis that were closely associated with the pathogenesis of IRI [40, 41]. For instance, Wang et al [42] indicated that BM-MSCs could protect the rats against IRI by enhancing the autophagy mediated by HO-1 (heme oxygenase-1).…”

Section: Immunomodulatory Role Of Mscs In Ltmentioning

confidence: 99%

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

Li,

Yu,

Chen

et al. 2023

Dig Dis

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Background: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants. Summary: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT. Key messages: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

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The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

Cited by 20 publications

References 102 publications

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

Role of Autophagy and Pyroptosis in Intervertebral Disc Degeneration

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

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