Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage DOI
Ye Yuan, Xiao Yang, Yutong Zhao

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown upregulate FTMT. However, the effects of FTMT upregulation by on neuronal ferroptosis GMH and its underlying mechanism not investigated. our study, 389 Sprague-Dawley rat pups postnatal day 7 were used establish collagenase-induced model an iron-overload intracerebral FeCl 2 injection. The expressions FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) acyl-CoA synthase long-chain family member 4 (ACSL4) increased GMH. agonist improved neurological deficits hydrocephalus or Adenovirus-FTMT enhanced YAP phosphorylation at Ser 127 site attenuated ferroptosis, which was reversed NDRG1 CRISPR Knockout. Iron overload induced deficits, Collectively, reduced via NDRG1/YAP signaling pathway may serve as potential non-invasive treatment for patients.

Language: Английский

DOXORUBICIN-RELATED CARDIOTOXICITY: REVIEW OF FUNDAMENTAL PATHWAYS OF CARDIOVASCULAR SYSTEM INJURY DOI
Ashot Avagimyan, Nana Pogosova, L. V. Kakturskiy

et al.

Cardiovascular Pathology, Journal Year: 2024, Volume and Issue: 73, P. 107683 - 107683

Published: Aug. 6, 2024

Language: Английский

Citations

12
Knocking Down Ferredoxin 1 Inhibits the Progression of Colorectal Cancer and Regulates Cuproptosis via Mediating the Hippo Signaling Pathway DOI Open Access
Ying Hu, Haihua Liu,

Xiaobin Tan

et al.

Molecular Carcinogenesis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

ABSTRACT Cuproptosis is a form of programmed cell death dependent on mitochondrial respiration and crucial in cancer treatment. The study attempted to screen cuproptosis‐associated genes colorectal (CRC) reveal regulatory pathways. Weighted gene co‐expression network analysis (WGCNA) was applied the modules based expression CRC patients. were screened at intersection cuproptosis data set. RNA sequencing performed assess transcriptome changes, followed by functional enrichment analyses potential Ferredoxin 1 (FDX1) knocked down vivo vitro experiments investigate effects FDX1 knockdown progression cuproptosis. found as highly expressed tumor cells. Knockdown regulated cells, inhibited growth, migration invasion. We 1956 upregulated DEGs 2201 downregulated si‐FDX1 which mainly enriched mitogen‐activated protein kinase (MAPK) signaling pathway, necrosis factor (TNF) pathway Hippo pathway. increasing levels dihydrolipoamide S‐succinyltransferase (DLST), lipoic acid synthetase (LIAS) phosphorylation Yes‐associated (pYAP)/YAP, transcriptional coactivator with PDZ‐binding domain (TAZ). inhibitor GA‐017 blocked this process. Knocking mediating shed new insights into development biomarkers for

Language: Английский

Citations

1
AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis DOI Creative Commons

Junxiong Zhao,

Ting Yang,

Jiali Yi

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109321 - 109321

Published: Feb. 23, 2024

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether could improve doxorubicin-induced induced significant fibrosis while suppressing mitophagy-related proteins elevating pyroptosis-related proteins. Conversely, reverses these effects, enhancing mitophagy inhibiting pyroptosis. In vitro experiments revealed inhibited H9c2 cardiomyocyte pyroptosis, improved impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, upregulated AMPK-ULK1-FUNDC1 expression. contrast, AMPK inhibitor (dorsomorphin) ULK1 (SBI-0206965) reversed antagonism FUNDC1-mediated secondary These results suggest mitochondria-targeted can antagonize pyroptosis impaired in cardiomyocytes via remodeling.

Language: Английский

Citations

7
Matrix stiffness-driven cancer progression and the targeted therapeutic strategy DOI Creative Commons
Rui Liang, Guanbin Song

Mechanobiology in Medicine, Journal Year: 2023, Volume and Issue: 1(2), P. 100013 - 100013

Published: Aug. 3, 2023

Increased matrix stiffness is a common phenomenon in solid tumor tissue and regulated by both mesenchymal cells. The increase collagen lysyl oxidase family proteins the extracellular leads to deposition, contraction, crosslinking of stroma, promoting increased tumors. Matrix critical progression various As mechanical factor microenvironment, involved progression, biological processes such as cell proliferation, invasion, metastasis, angiogenesis, drug resistance, immune escape. Reducing can slow down progression. Therefore targeting potential option for therapy. This article reviews detailed mechanisms different malignant phenotypes therapies stiffness. Understanding role tumors could provide theoretical insights into treatment assist clinical development new therapies.

Language: Английский

Citations

14
Innovative role of the antidepressant imipramine in esophageal squamous cell carcinoma treatment: Promoting apoptosis and protective autophagy DOI

Shihao Bao,

Yifan Zhang,

Jingtong Zeng

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113969 - 113969

Published: Jan. 6, 2025

Language: Английский

Citations

0
Peptide‐Drug Conjugate for Therapeutic Reprogramming of Tumor‐Associated Macrophages in Breast Cancer DOI Creative Commons
Anni Lepland, Elisa Peranzoni, Uku Haljasorg

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract In triple‐negative breast cancer (TNBC), pro‐tumoral macrophages promote metastasis and suppress the immune response. To target these cells, a previously identified CD206 (mannose receptor)‐binding peptide, mUNO was engineered to enhance its affinity proteolytic stability. The new rationally designed MACTIDE, includes trypsin inhibitor loop, from Sunflower Trypsin Inhibitor‐I. Binding studies recombinant revealed 15‐fold lower K D for MACTIDE compared parental mUNO. Mass spectrometry further demonstrated 5‐fold increase in MACTIDE's half‐life tumor lysates Homing TNBC‐bearing mice shows that fluorescein (FAM)‐MACTIDE precisely targeted + tumor‐associated (TAM) upon intravenous, intraperitoneal, even oral administration, with minimal liver accumulation. conjugated Verteporfin, an FDA‐approved photosensitizer YAP/TAZ pathway create conjugate MACTIDE‐V. orthotopic 4T1 TNBC mouse model, non‐irradiated MACTIDE‐V‐treated exhibited anti‐tumoral effects comparable those treated irradiated MACTIDE‐V, fewer signs of toxicity, prompting investigation into laser‐independent activity conjugate. vitro using bone marrow‐derived showed MACTIDE‐V excluded YAP nucleus, increased phagocytic activity, upregulated several genes associated cytotoxic macrophages. models TNBC, slowed primary growth, suppressed lung metastases, markers phagocytosis antigen presentation TAM monocytes, increasing infiltration lymphocyte subsets. is proposed as promising peptide‐drug modulating macrophage function immunotherapy.

Language: Английский

Citations

0
Hippo pathway activation mediates cardiomyocyte ferroptosis to promote dilated cardiomyopathy through downregulating NFS1 DOI Creative Commons
Gang She,

Xinyue Hai,

Lin-Chun Jia

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103597 - 103597

Published: March 1, 2025

Language: Английский

Citations

0
Pharmacological regulators of Hippo pathway: Advances and challenges of drug development DOI Open Access
Zhaobai Lao, Xin Chen, Bin Pan

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 18, 2025

Abstract The Hippo signaling pathway is crucial in regulating organ size, tumor progression, tissue regeneration, and bone homeostasis. Inactivation of the results nuclear translocation activation YAP/TAZ. This not only promotes progression but also enhances wound healing, maintenance stability Although its discovery occurred over two decades ago, developing effective inhibitors or activators for remains challenging. Recently, however, pace advancements signaling‐related agonists antagonists has accelerated, with some drugs that target TEAD advancing to clinical trials showing promise treating related diseases. review summarizes progress research on inhibitors, offering an in‐depth analysis their regulatory mechanisms, pharmacological properties, potential vivo applications.

Language: Английский

Citations

0
Pathophysiology of Doxorubicin-Mediated Cardiotoxicity DOI Creative Commons
Roberto Arrigoni, Emilio Jirillo, Carlo Caiati

et al.

Toxics, Journal Year: 2025, Volume and Issue: 13(4), P. 277 - 277

Published: April 5, 2025

Doxorubicin (DOX) is used for the treatment of various malignancies, including leukemias, lymphomas, sarcomas, and bladder, breast, gynecological cancers in adults, adolescents, children. However, DOX causes severe side effects patients, such as cardiotoxicity, which encompasses heart failure, arrhythmia, myocardial infarction. DOX-induced cardiotoxicity (DIC) based on combination nuclear-mediated cardiomyocyte death mitochondrial-mediated death. Oxidative stress, altered autophagy, inflammation, apoptosis/ferroptosis represent main pathogenetic mechanisms responsible DIC. In addition, vitro vivo models DIC sirtuins (SIRT), especially, SIRT 1 are reduced, this event contributes to cardiac damage. fact, inhibits reactive oxygen species NF-kB activation, thus improving oxidative stress remodeling. Therefore, recovery during may a therapeutic strategy limit progression. Natural products, i.e., polyphenols, well nano formulations iron chelators, other potential compounds experimented with At present, few clinical trials available confirm efficacy these products The aim review description pathophysiology drug targets alleviate

Language: Английский

Citations

0
Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect DOI Creative Commons
Z. Zhang, Lin Li, Yu-Chen Ge

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract In situ radiotherapy is the most successful cytotoxic therapy available for treatment of solid tumors, while high‐dose per fraction not yet widely and reliably used. To some extent, major considerations disappointing results are on risk irradiation‐induced damage to surrounding normal tissues difficulty in distant metastasis control. break these restraints, a gelatinase‐responsive amphiphilic methoxypolyethyleneglycol–PVGLIG–polycaprolactone (mPEG–PVGLIG–PCL) nanoparticles’ loading verteporfin (N@VP), special photosensitizer that can also be excited by X‐rays produce singlet oxygen greatly enhance efficacy, prepared this study. Herein, it shown formed N@VP combined with conventional‐dose radiation (RT, 2 Gy (gray, dose unit)) realize an antitumor effect no less than RT (8 Gy) minimize necessary achieve local tumor Moreover, radiosensitive nanosystem exert excellent systemic immunity abscopal effect, providing preferable “in vaccine” strategy based efficient management metastasis. When immunotherapy, novel radiosensitization better immunotherapy sensitivity stimulating significant immunogenic cell death synergistic immune responses.

Language: Английский

Citations

0