Inflammation, Journal Year: 2024, Volume and Issue: unknown
Published: May 13, 2024
Language: Английский
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Jan. 18, 2024
The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, process critical to the body’s immune response, particularly combatting bacterial infections, impeding tumor invasion, and contributing pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting effector cells, creating an microenvironment, initiating pyroptosis. This article serves as introduction GSDM protein-mediated pyroptosis providing overview GSDMs’ involvement immunity. Additionally, we explore potential applications GSDMs both innovative established antitumor strategies.
Language: Английский
Citations
10
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Aug. 30, 2024
Due to low success rates and long cycles of traditional drug development, the clinical tendency is apply omics techniques reveal patient-level disease characteristics individualized responses treatment. However, heterogeneous form data uneven distribution targets make discovery precision medicine a non-trivial task. This study takes pyroptosis therapy for triple-negative breast cancer (TNBC) as paradigm uses mining large TNBC cohort databases establish biofactor-regulated neural network rapidly screening optimizing compound pairs. Subsequently, biomimetic nanococrystals are prepared using preferred combination mitoxantrone gambogic acid rational delivery. The unique mechanism obtained regulating genes through ribosomal stress triggering cascade immune effects revealed in models. In this work, target omics-based intelligent framework explores an innovative development paradigm, which repurposes existing drugs enables precise treatment refractory diseases.
Language: Английский
Citations
10
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7)
Published: March 22, 2024
Abstract SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis tumour cells. However, underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three cell lines were treated with CCK‐8 assessed cytotoxicity. Transcriptome was performed on Illumina platform verified qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T‐SOD), Fe, glutathione (GSH) oxidized (GSSG) measured. induced death time‐ dose‐dependent, a more significant inhibitory effect MDA‐MB‐231 Fer‐1, GSH Vitamin C attenuated effects but not erastin. RNA‐Seq analysis revealed that treatment significantly enriched differentially expressed genes related ferroptosis. Furthermore, increased intracellular MDA, iron ion, GSSG levels while decreasing T‐SOD, (T‐GSH), levels.SBFI26 dose‐dependently up‐regulates expression HMOX1 ALOX12 at both gene levels, promoting Similarly, it increases SAT1, ALOX5, ALOX15, ALOXE3 CHAC1 that, downregulating NFE2L2 inhibit leads cellular accumulation fatty acids, triggers excess ferrous ions subsequent lipid peroxidation for inducing
Language: Английский
Citations
9
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116254 - 116254
Published: Feb. 16, 2024
Language: Английский
Citations
8
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 130825 - 130825
Published: March 15, 2024
Language: Английский
Citations
8
Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(44)
Published: May 25, 2024
Abstract The vigorous development of cancer nanomedicine has revolutionized traditional oncology medicine, but it is also limited by the continuous mutation cunning cells, leading to apoptosis insensitivity and therapeutic disappointment. Inflammatory‐regulated cell death (RCD), especially pyroptosis‐related death, demonstrates huge potential for sensitization due its unique biochemical characteristics. aim this research present a thorough synopsis current knowledge on pyroptosis‐associated inflammatory including pyroptosis, cuproptosis, PANoptosis, synergistic function in nano therapy. Paradigm studies death‐mediated apoptosis‐sensitizing tumor nanotherapeutics are introduced detail, coordination mechanisms based nanomaterials discussed. In addition, multi‐angle analysis future prospects pyroptosis‐sensitized various emphasized further expand application scope RCD. It believed that emerging auxiliary treatments RCD will greatly promote progress nanomedicine.
Language: Английский
Citations
7
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: April 20, 2024
Abstract Pyroptosis, a novel type of programmed cell death (PCD), which provides feasible therapeutic option for the treatment tumors. However, due to hypermethylation promoter, critical protein Gasdermin E (GSDME) is lacking in majority cancer cells, cannot start pyroptosis process and leads dissatisfactory effects. Additionally, quick clearance, systemic side effects, low concentration at tumor site conventional reagents restrict their use clinical therapy. Here, we described combination therapy that induces via ultrasound-targeted microbubble destruction (UTMD) with DNA demethylation. The combined application UTMD hydralazine-loaded nanodroplets (HYD-NDs) can lead rapid release HYD (a demethylation drug), cause up-regulation GSDME expression, produce reactive oxygen species (ROS) by cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs ultrasound (US) group had strongest inhibition effect, rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US 32.73%±7.72%), indicating strategy more significant synergistic anti-tumor effect. In addition, as new drug delivery carrier, have great biosafety, targeting, imaging performance. According results, reasonably regulated pyroptosis, offered optimizing GSDME-silenced solid
Language: Английский
Citations
6
Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(8), P. 3856 - 3876
Published: May 18, 2024
Abstract Enhancement of malignant cell immunogenicity to relieve immunosuppression lung cancer microenvironment is essential in treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind phytopharmaceutical, effective inhibiting cells and boosting their immunogenicity, while the initial target DHA's intracellular action poorly understood. The present in‐depth analysis aims reveal influence DHA on highly expressed TOM70 mitochondrial membrane cancer. affinity was analyzed by microscale thermophoresis (MST), pronase stability, thermal stability. functions underlying mechanism were investigated using western blots, qRT‐PCR, flow cytometry, rescue experiments. inhibition resulted mtDNA damage translocation cytoplasm from mitochondria due disruption homeostasis. Further ex vivo findings also showed cGAS/STING/NLRP3 signaling pathway activated thereby underwent pyroptosis, leading enhanced presence DHA. Nevertheless, DHA‐induced mobilization synchronously attenuated when replenished. Finally, possess potent anti‐lung efficacy vitro vivo. Taken together, these data confirm an important for disturb homeostasis, which further activates STING arouses pyroptosis strengthen against thereupon. study provides vital clues phytomedicine‐mediated anti‐tumor therapy.
Language: Английский
Citations
6
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Nov. 2, 2023
Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by swelling, cytomembrane perforation lysis, chromatin DNA fragmentation, the release intracellular proinflammatory contents, such as Interleukin (IL) 8, IL-1β, ATP, IL-1α, high mobility group box 1 (HMGB1). Our understanding pyroptosis has increased over time with an increase in research on subject: gasdermin-mediated lytic PCD usually, but not always, requires cleavage caspases. Moreover, new evidence suggests that induction tumor cells results strong inflammatory response significant cancer regression, which stimulated great interest among scientists for its potential application clinical therapy. It’s worth noting side effects chemotherapy radiotherapy can be triggered pyroptosis. Thus, intelligent use pyroptosis, double-edged sword tumors, will enable us to understand genesis development cancers provide methods develop anticancer drugs based Hence, this review, we systematically summarize molecular mechanisms latest available supporting antitumor properties summary various medicines targeting signaling pathways.
Language: Английский
Citations
16
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1285 - 1285
Published: Jan. 9, 2023
Pyroptosis is a programmed cell death characterized by the rupture of plasma membranes and release cellular content leading to inflammatory reaction. Four mechanisms inducing pyroptosis have been reported thus far, including (i) caspase 1-mediated canonical, (ii) 4/5/11-mediated non-canonical, (iii) 3/8-mediated (iv) caspase-independent pathways. Although discovered as defense mechanism protecting cells from infections intracellular pathogens, plays roles in tumor initiation, progression metastasis tumors, well treatment response antitumor drugs and, consequently, patient outcome. induction following therapies has several types, lung, colorectal gastric cancer, hepatocellular carcinoma melanoma. This review provides an overview pathways discusses therapeutic potential particularly
Language: Английский
Citations
15