RIPK1 Pre-design Chimera RNAi
- Known as:
- RIPK1 Pre-design Chimera RNAi
- Catalog number:
- H00008737-R02
- Product Quantity:
- 20 nmol
- Category:
- -
- Supplier:
- Abno
- Gene target:
- RIPK1 Pre-design Chimera RNAi
Related genes to: RIPK1 Pre-design Chimera RNAi
- Gene:
- RIPK1 NIH gene
- Name:
- receptor interacting serine/threonine kinase 1
- Previous symbol:
- -
- Synonyms:
- RIP
- Chromosome:
- 6p25.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-07
- Date modifiied:
- 2015-11-17
Related products to: RIPK1 Pre-design Chimera RNAi
Related articles to: RIPK1 Pre-design Chimera RNAi
- Licoricidin (LCD), a natural isoflavonoid compound extracted from Glycyrrhiza species, has been extensively demonstrated to possess diverse biological activities, including anti-inflammatory and potent anti-cancer effects. However, the precise mechanism underlying LCD action against hepatocellular carcinoma (HCC) remains unclear, particularly regarding its regulation of cell death. In this study, we comprehensively explored the effects of LCD on HCC cells and investigated its role and mechanism of action in the induction of PANoptosis. Our results reveal that LCD exhibited potent anti-HCC activities by decreasing cell viability and significantly inhibiting clonogenic survival in HCC cell lines. Our results demonstrate that LCD triggered a substantial accumulation of reactive oxygen species and induced depolarization of the mitochondrial membrane, leading to profound mitochondrial dysfunction. We further confirmed that LCD activated a comprehensive PANoptosis program by synchronously upregulating the expression of apoptotic proteins (Bax, c-CASP3, and c-PARP1), pyroptotic proteins (c-CASP 1 and c-GSDMD), and the phosphorylation of necroptotic executioners (p-MLKL and p-RIPK1). Treatment with the ROS inhibitor (NAC), apoptosis inhibitor (ZVAD), or necroptosis inhibitor (Nec-1) significantly reduced the expression of PANoptosis-related proteins in LCD-treated cells. Furthermore, molecular docking simulations and cellular thermal shift assay (CETSA) assay confirmed the direct and stable binding of LCD to PANoptosis-related proteins. In summary, we show for the first time that LCD exerts favorable anti-HCC activities via the induction of PANoptosis through a ROS-dependent mechanism and potntial direct modulation of core executive proteins. This multi-target action suggests that LCD could be a novel candidate for the management of hepatocellular carcinoma. - Source: PubMed
Publication date: 2026/07/13
Hung Ming-ChunChiou Hui-LingHsieh Yi-HsienChen Pei-NiYu Yung-LuenLee Hsiang-Lin - Recurrence and metastasis are the leading causes of mortality in renal cell carcinoma (RCC), and its intrinsic drug resistance further limits effective therapeutic options. Synergistic activation of multiple regulated cell death pathways has recently emerged as a novel approach to overcome therapeutic resistance. Here, we developed two mitochondria-targeted iridium(III) photosensitizers, Ir-MT1 and Ir-MT2, for synergistic photoimmunotherapy of RCC. Upon white-light irradiation, Ir-MT1/2 induced severe mitochondrial damage and dysfunction, leading to massive release of mitochondrial contents. Mitochondrial DNA leakage activated the cGAS-stimulator of interferon genes pathway and caspase-1-mediated pyroptosis cascade, whereas excessive Ca efflux promoted RIPK1/RIPK3 phosphorylation and induced necroptosis. These death signals facilitated pore formation by gasdermin D and mixed lineage kinase domain-like protein in the plasma membrane, resulting in membrane rupture, release of damage-associated molecular patterns, and immunogenic cell death synergistically. In vivo, Ir-MT1/2 not only effectively suppressed primary tumor growth but also eliminated distant tumors through activation of anti-tumor immunity, exhibiting potent therapeutic efficacy and favorable biosafety. Overall, our work provides the evidence that a single iridium complex can simultaneously trigger pyroptosis-necroptosis synergy, overcoming intrinsic drug resistance and offering a promising strategy for multi-network systemic therapy of RCC. - Source: PubMed
Publication date: 2026/07/28
Qin XinChen Meng-DiGao WenqiWang YipingLiu Lin-QingTeng ZhenQi TienanWang QiyuanWang YuxuanLi DaoxiangYan KeqiangPan LingZhao ZhongweiZhao ShuoWang Kang-NanFu ShuaiYu Nengwang - Cell death is a key effector mechanism of the innate immune system for host defense. While it is beneficial for pathogen clearance, excess lytic cell death is linked to inflammation, pathology, and disease. Therefore, tight regulation of cell death execution is critical. PANoptosis is an innate immune, lytic, and inflammatory cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs, with roles in infection, inflammatory disease, and cancer. During PANoptosis, caspases and RIPKs within PANoptosome complexes activate multiple executioner proteins, including gasdermin (GSDM) family proteins and mixed lineage kinase domain-like pseudokinase (MLKL). These executioners form membrane pores that lead to membrane lysis and the release of DAMPs and cytokines. Although multiple executioners are activated during PANoptosis, the requirement for individual executioners in driving the lytic cell death remains unclear. To address this, we performed a comprehensive genetic analysis of GSDMD, GSDME, and MLKL using single, double, and triple knockout primary macrophages across triggers known to activate distinct PANoptosomes. Deletion of individual executioners did not reduce the activation of caspases or other executioners and did not fully block PANoptosis, suggesting these executioner molecules often act in a compensatory manner to execute PANoptosis. Furthermore, combined deletion of all three executioners provided greater protection than any single or double deletion. However, residual cell death still occurred even after genetic deletion of all three executioner proteins, suggesting the involvement of additional executioners that remain to be identified. Overall, our study suggests that targeting individual executioners will not be sufficient in disease contexts where PANoptosis drives pathology, and targeting the full executioner network or upstream molecules, such as sensors or essential PANoptosome complex components, will be needed for therapeutic efficacy in infection, inflammatory disease, and cancer. - Source: PubMed
Publication date: 2026/07/28
Indari OmkarGiri PrashantTweedell Rebecca EKanneganti Thirumala-Devi - In numerous demyelinating diseases, brain tissue exhibits excessive inflammatory responses that promote the activation of immune cells, thereby exacerbating cellular damage and amplifying inflammatory cascades. Emerging evidence highlights receptor-interacting protein kinase 1 (RIPK1) is a pivotal regulator of neuroinflammation, and its dysregulation contributes to the pathogenesis of various central nervous system (CNS) disorders. While our previous work established that RIPK1 kinase inhibition promotes remyelination in acute demyelinating models, however, the precise mechanisms of RIPK1 in microglial activation remain unclear. Here, to investigate RIPK1's role in microglial polarization, we employed lipopolysaccharide (LPS)-stimulated BV2 cells and the lysolecithin (LPC)-induced demyelination mouse model. By combining RIPK1 kinase-dead knock-in mice and the pharmacological inhibitor Nec-1s，we performed experiments in both in vitro and in vivo models. We demonstrated that RIPK1 inhibition significantly attenuates M1 microglial polarization and pro-inflammatory cytokine production. Mechanistically, we identified that RIPK1 orchestrates the expression of colony-stimulating factor 3 (Csf3), which subsequently activates the JAK2/STAT3 signaling pathway. Pharmacological inhibition of RIPK1 decreased Csf3 expression, leading to reduced phosphorylation of JAK2/STAT3 and subsequent suppression of M1 polarization. Our findings reveal a novel RIPK1-Csf3-JAK2/STAT3 signaling axis governing microglial polarization and highlight its potential as a therapeutic target for demyelinating diseases. - Source: PubMed
Publication date: 2026/07/26
Yang ShuyingZhou XinZhang JingPan NaLiu MengtingSong Haibo - Autoimmune diseases (AIDs) are chronic inflammatory disorders in which loss of self-tolerance intersects with tissue stress and damage. Increasing evidence indicates that regulated cell death (RCD) can act as an upstream amplifier in selected autoimmune settings, while in other settings it may mainly report downstream collateral injury caused by cytotoxic lymphocytes, immune complexes, complement activation, or tissue hypoxia. Accordingly, this review distinguishes causal death execution from associative pathway signatures and highlights the types of longitudinal, cell-type-resolved, and perturbational evidence needed to make that distinction. We summarize how apoptosis, necroptosis, pyroptosis, and ferroptosis operate as an interlocking network in autoimmune microenvironments, frequently co-existing as context-dependent mixed-death states driven by shared triggers such as cytokines, PRR ligands, and oxidative stress, and governed by decision hubs including RIPK1 and caspase-8. We highlight integrated concepts such as PANoptosis to explain pathway convergence and compensatory switching into parallel lytic branches when a single node is constrained. The review further connects mechanistic insights to translational priorities, emphasizing biomarker strategies that report pathway engagement, targeted modulation of executors or upstream sensing and cytokine circuits, and lesion-localized delivery approaches to improve the therapeutic window. Finally, we outline key gaps that must be addressed to enable precision interventions, including spatial and cell-type resolved validation of death programs, longitudinal profiling across flare-remission trajectories, and harmonized composite panels capable of capturing mixed-death dynamics in heterogeneous AIDs. - Source: PubMed
Publication date: 2026/07/25
Cai XiaoyuYao Yao