Nrf2/UBE3B protects against acute lung injury by inhibiting ferritinophagy through the ubiquitination of NCOA4 DOI Creative Commons

Yanjun Wang,

Hui Dong, Yunfan Gu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Iron overload and ferroptosis are associated with intestinal ischemia reperfusion (II/R)-induced acute lung injury (ALI). However, the mechanisms underlying regulation of iron homeostasis remain unclear. Nrf2 regulates cellular homeostasis; however, its impact on ALI pathology mechanism action requires further investigation. Ubiquitin ligase E3B (UBE3B) plays a critical role in proteasome pathway, which is essential for protein turnover ubiquitin-mediated signaling. A recent study found that UBE3B oxidative stress; it remains unknown whether related to Nrf2. Furthermore, exact largely uncharacterized. In present study, immunohistochemical analysis expression type II alveolar epithelial cells (AECII) was conducted be increased II/R-ALI. Western blot indicated hyperactivation may alleviate stress, thereby protecting against ALI. Moreover, involved metabolism dysfunction ferroptosis. deficiency enhanced process nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy ferrous ion content, whereas overexpression reversed harmful effects knockdown AECⅡ, promote AECⅡ This highlights Nrf2/UBE3B/NCOA4 axis II/R-ALI pathogenesis, suggesting activation promising strategy treatment.

Language: Английский

Protein modification and degradation in ferroptosis DOI Creative Commons

Yuan Wang,

Yan Ding, Jinbao Liu

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103259 - 103259

Published: June 27, 2024

Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, modification. modifications play pivotal roles in regulating protein stability, activity, localization, interactions, ultimately influencing both the buildup iron lipid peroxidation. In mammalian cells, regulators ferroptosis typically degradation via two principal pathways: ubiquitin-proteasome which handles majority degradation, autophagy, primarily targeting long-lived or aggregated This comprehensive review aims to summarize recent advances modification linked ferroptosis. It also discusses strategies for modulating systems, providing new insights into potential therapeutic applications cancer non-neoplastic diseases.

Language: Английский

Citations

16
Artemisinin and Its Derivatives as Potential Anticancer Agents DOI Creative Commons

L Y Wen,

Ben Chung-Lap Chan, Ming‐Hua Qiu

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(16), P. 3886 - 3886

Published: Aug. 16, 2024

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. (qinghao). and its derivatives share an unusual endoperoxide bridge are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin have been reported exhibit promising anticancer effects in recent decades. this review, we focused on research progress of with potential activities. The pharmacological effects, mechanisms, clinical trials cancer therapy were discussed. This review may facilitate future exploration as effective agents.

Language: Английский

Citations

8
EPAS1, a hypoxia‐ and ferroptosis‐related gene, promotes malignant behaviour of cervical cancer by ceRNA and super‐enhancer DOI Creative Commons
Xiaoqin Lu, Wenyi Zhang, Jingyan Zhang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(9)

Published: May 1, 2024

Abstract Hypoxia and Ferroptosis are associated with the malignant behaviour of cervical cancer. Endothelial PAS domain‐containing protein 1 (EPAS1) contributes to progression EPAS1 plays important roles in hypoxia ferroptosis. Using GEO dataset, machine‐learning algorithms were used screen for hypoxia‐ ferroptosis‐related genes (HFRGs) was identified as hub gene. qPCR WB investigate expression normal cancer tissues. The proliferation, invasion migration cells HeLa SiHa cell lines detected using CCK8, transwell wound healing assays, respectively. Apoptosis by flow cytometry. A dual‐luciferase assay analyse MALAT1‐miR‐182‐5P‐EPAS1 mRNA axis core promoter elements super‐enhancer. significantly overexpressed could increase invasion, reduce apoptosis cell. According double‐luciferase assay, regulated MALAT1‐Mir‐182‐5p‐EPAS1 axis. is super‐enhancers. Double‐luciferase showed that super‐enhancer E1 E3. EPAS1, an HFRG, promotes cells. super‐enhancers MALAT1‐miR‐182‐5P‐ may be a target diagnosis treatment

Language: Английский

Citations

7
Synergistic anticancer therapy via ferroptosis using modified bovine serum albumin nanoparticles loaded with sorafenib and simvastatin DOI
Kaushik Kuche,

Vivek Yadav,

M. Dharshini

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 127254 - 127254

Published: Oct. 7, 2023

Language: Английский

Citations

15
Molecular insights into artemisinin resistance in Plasmodium falciparum: An updated review DOI Creative Commons
Wihda Aisarul Azmi,

Andita Fitri Mutiara Rizki,

Yenny Djuardi

et al.

Infection Genetics and Evolution, Journal Year: 2023, Volume and Issue: 112, P. 105460 - 105460

Published: June 1, 2023

Malaria still poses a major burden on human health around the world, especially in endemic areas. Plasmodium resistance to several antimalarial drugs has been one of hindrances control malaria. Thus, World Health Organization recommended artemisinin-based combination therapy (ACT) as front-line treatment for The emergence parasites resistant artemisinin, along with ACT partner drugs, led failure. artemisinin is mostly related mutations propeller domain kelch13 (k13) gene that encodes protein Kelch13 (K13). K13 an important role parasite reaction oxidative stress. most widely spread mutation K13, highest degree resistance, C580Y mutation. Other mutations, which are already identified markers R539T, I543T, and Y493H. objective this review provide current molecular insights into falciparum. trending use beyond its effect described. Immediate challenges future research directions discussed. Better understanding mechanisms underlying will accelerate implementation scientific findings solve problems malarial infection.

Language: Английский

Citations

14
Dihydroartemisinin induces ferroptosis in T cell acute lymphoblastic leukemia cells by downregulating SLC7A11 and activating the ATF4‑CHOP signaling pathway DOI Open Access
Na Tang, Xinling Liu, Yongxin Liu

et al.

Oncology Letters, Journal Year: 2024, Volume and Issue: 28(1)

Published: May 24, 2024

The present study aimed to investigate the anti‑leukemic effects of dihydroartemisinin (DHA) on T‑cell acute lymphoblastic leukemia (T‑ALL) cell lines, Jurkat and Molt‑4, underlying mechanisms. Cell Counting Kit‑8 was performed measure viability. apoptosis cycle distribution were assessed by flow cytometry. expression levels ATF4 CHOP mRNA reverse transcription‑quantitative PCR, while protein abundance SLC7A11, GPX4, determined western blotting. Moreover, malondialdehyde, glutathione (GSH) reactive oxygen species (ROS) assays used detect ferroptosis. results showed that DHA suppressed T‑ALL viability in vitro, induced arrest at S or G2/M phase. also ROS burst, activated endoplasmic reticulum (ER) stress, disrupted system Xc‑‑GSH‑GSH peroxidase 4 antioxidant system, increased lipid peroxide accumulation, resulting in death. By contrast, pharmacological inhibition ferroptosis alleviated DHA‑induced death, confirming induces death via Mechanistically, effect partly mediated downregulating SLC7A11 upregulating ATF4‑CHOP signaling pathway, which is associated with ER stress. These indicated may induce lines could represent a promising therapeutic agent for treating T‑ALL.

Language: Английский

Citations

6
Enhancing anti-cancer potential by delivering synergistic drug combinations via phenylboronic acid modified PLGA nanoparticles through ferroptosis-based therapy DOI Open Access
Kaushik Kuche,

Vivek Yadav,

Meet Patel

et al.

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 156, P. 213700 - 213700

Published: Nov. 14, 2023

Language: Английский

Citations

11
The dual role of ferroptosis in anthracycline-based chemotherapy includes reducing resistance and increasing toxicity DOI Creative Commons
Jiazheng Zhao, Ning Zhang, Xiaowei Ma

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 21, 2023

Abstract In conjunction with previous studies, we have noted that ferroptosis, as an emerging mode of regulated cell death (RCD), is intimately related to anthracycline pharmacotherapy. Not only does ferroptosis significantly modulate tumour resistance and drug toxicity, which are core links the relevant chemotherapeutic process, but it also appears play a conflicting role has yet be appreciated. By targeting dual in anthracycline-based chemotherapy, this review aims focus on latest findings at stage, identify potential associations provide novel perspectives for subsequent research directions therapeutic strategies.

Language: Английский

Citations

10
HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China DOI Creative Commons

Chunrong Han,

Wanqiu Huang, Ye Mei

et al.

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 28, 2023

To explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues central eastern China to provide theoretical basis for cancer screening prophylactic HPV vaccine development China. DNA was extracted from paraffin-embedded CSCC samples exfoliated cells populations. 23 genotypes were detected by combining polymerase chain reaction (PCR) reverse dot hybridized gene chip detection technology 2,306 10,245 The infection analyzed. overall HPVs patients 92.71%. frequency single-type multiple-type 86.48% 13.51%, respectively. most common Chinese HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, HPV-59. these eight high-risk (HR-HPV) HPV-positive as high 96.91%. Of which seven HR-HPV related nine-valent vaccines 95.09%. Meanwhile, rates low-risk (LR-HPV) female aged 35-64 years who underwent 13.16% 1.32%, high-frequency women HPV-53, HPV-68, HPV-39, HPV-51, HPV-56, with 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, 0.74%, Among screened China, detecting 8 can reduce technical difficulty reagent costs, while also improving efficiency effectiveness screening. genotyping assists gynecologists assessing risk HR-HPV-positive intraepithelial neoplasia guiding them implementing appropriate interventions. Furthermore, is helpful doctors follow up evaluate protective effect vaccine.

Language: Английский

Citations

10
Erastin induces ferroptosis in cervical cancer cells via Nrf2/HO-1 signaling pathway DOI Creative Commons
Xiaoning Wei, Qiaoqiao Huang,

Jinbing Huang

et al.

International Journal of Immunopathology and Pharmacology, Journal Year: 2023, Volume and Issue: 37

Published: Jan. 1, 2023

Objective Our research aims to assess the influence of erastin, a ferroptosis-inducing agent, on cervical cancer cells. Introduction Cervical is prevalent malignancy in females. Dysregulation ferroptosis, form cell demise reliant iron, implicated several cancers. Methods The effect erastin HeLa and SiHa was detected by transwell assay, scratch test, colony formation while apoptosis using flow cytometry. Cellular reactive oxygen species (ROS) generation dichloro-dihydro-fluorescein diacetate assay. Sequencing analysis identified differentially expressed genes (DEGs), Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) Enrichment analyses were employed identify target gene. Subsequently, utilization small interfering RNA (siRNA) suppress targeted gene expression cells, thereby effectively mitigating impact various cellular processes including invasion, formation, migration, ROS generation. Results findings indicate that attenuates viability both cells (IC 50 = 30.88 µM) 29.40 µM). Treatment with at 10 µM inhibits migration within 24 h. Ferrostatin-1 (1 notably alleviates inhibitory effects Upregulation nuclear factor erythroid 2-related 2 (Nrf2) its downstream target, heme oxygenase-1 (HO-1), found erastin-treated compared control group. When knocked down HO-1 counteracting production Conclusion demonstrates induces ferroptosis accumulation activating Nrf2/HO-1 pathway, significantly reducing proliferation motility. These propose potential molecular mechanism erastin-mediated development.

Language: Английский

Citations

10