Investigating the role of disulfidptosis related genes in radiotherapy resistance of lung adenocarcinoma DOI Creative Commons

Xiaoxia Pan,

Hongyan Qian,

Zhouna Sun

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 23, 2024

Background Radiotherapy resistance is an important reason for high mortality in lung cancer patients, but the mechanism still unclear. Dysregulation of cell proliferation and death plays a crucial role onset progression adenocarcinoma (LUAD). In recent times, novel form cellular demise called disulfidptosis, has attracted increasing attention. However, it unclear whether radiation-related disulfidptosis genes have prognostic LUAD. Methods A complete suite bioinformatics tools was used to analyze expression significance genes. Afterward, we investigated predictive risk signature tumor microenvironments (TME), somatic mutations, immunotherapies. addition, conducted series experiments verify differentially expressed radiotherapy related (DERRDGs) vitro . Results total 88 DERRDGs were found. We constructed validated model based on PRELP, FGFBP1, CIITA COL5A1. The enrichment analysis showed DERRDG affected prognosis by influencing (TME) immunotherapy. And nomogram promote clinical application. q-PCR confirmed significant differences between A549 irradiation-resistance A549. Finally, western-blot, IHC staining, small interference experiment suggested that PRELP may be potential biomarker resistance, whose low associated with poor outcomes LUAD patients. Conclusion This study reveals possible underlying mechanisms discovered key gene which helps identify new biomarkers provides basis future research.

Language: Английский

Selenium Attenuates Radiation Colitis by Regulating cGAS‐STING Signaling DOI Creative Commons
Xuefeng Qian, Haoqiang Lai,

Haimei Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Radiation colitis is one of the most common complications in patients undergoing pelvic radiotherapy and there no effective treatment clinic. Therefore, searching for agents radiation urgently needed. Herein, it found that essential element selenium (Se) protective against through inhibiting X‐ray‐induced apoptosis, cell cycle arrest, inflammation with involvement balancing generation reactive oxygen species after irradiation. Mechanistically, Se, especially nanoparticles (SeNPs), induced selenoprotein expression then functioned to effectively restrain DNA damage response, which reduced intestinal injury. Additionally, SeNPs also restrained cyclic GMP‐AMP synthas (cGAS)‐ stimulator interferon genes (STING)‐TBK1‐IRF3 signaling pathway cascade, thereby blocking transcription inflammatory cytokine gene, IL‐6 TNF‐α, thus alleviating inflammation. Moreover, inducing expression, such as GPX4, vivo can regulate microenvironment immunity gut microbiota attenuate radiation‐induced by oxidative stress maintaining homeostasis. Together, these results unravel a previously unidentified modulation role but suppressing cGAS‐STING‐TBK1‐IRF3 cascade.

Language: Английский

Citations

8
Mitochondria‐Modulating Liposomes Reverse Radio‐Resistance for Colorectal Cancer DOI Creative Commons

Junmei Li,

Yuhong Wang,

Wenhao Shen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 23, 2024

Complete remission of colorectal cancer (CRC) is still unachievable in the majority patients by common fractionated radiotherapy, leaving risks tumor metastasis and recurrence. Herein, clinical CRC samples demonstrated a difference phosphorylation translation initiation factor eIF2α (p-eIF2α) activating transcription 4 (ATF4), whose increased expression initial X-ray irradiation led to resistance subsequent radiotherapy. The underlying mechanism studied radio-resistant CT26 cells, revealing that incomplete mitochondrial outer membrane permeabilization (iMOMP) triggered key for elevated p-eIF2α ATF4, therefore radio-resistance. This finding guided discover metformin 2-DG are synergistic reversing radio inhibiting ATF4. Liposomes loaded with (M/D-Lipo) thus prepared enhancing radiotherapy CRC, which achieved satisfactory therapeutic efficacy both local metastatic tumors radio-resistance preventing T lymphocyte exhaustion.

Language: Английский

Citations

6
Radioresistance in rectal cancer: can nanoparticles turn the tide? DOI Creative Commons

Diogo Luiz Coelho,

Diogo Estêvão, Maria José Oliveira

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 30, 2025

Abstract Rectal cancer accounts for over 35% of the worldwide colorectal burden representing a distinctive subset cancers from those arising in colon. Colorectal exhibit continuum traits that differ with their location large intestine. Due to anatomical and molecular differences, rectal is treated differently colon cancer, neoadjuvant chemoradiotherapy playing pivotal role control locally advanced disease. However, radioresistance remains major obstacle often correlated poor prognosis. Multifunctional nanomedicines offer promising approach improve radiotherapy response rates, as well increase intratumoral concentration chemotherapeutic agents, such 5-Fluorouracil. Here, we revise main differences between tumors, exploring complex orchestration beyond most reported literature therapy rates. Graphical

Language: Английский

Citations

0
Establishment and biological characterization of radioresistant colorectal cancer cell lines DOI Creative Commons

Tianyin Qu,

Qing Dai, Jing Leng

et al.

FEBS Open Bio, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Radiotherapy resistance is a major cause of recurrence and metastasis in colorectal cancer (CRC). We established radiotherapy-resistant cell lines to explore the molecular mechanisms radiotherapy CRC. HT29 HCT116 cells were subjected repeated irradiation at 2 Gy establish these lines. CCK-8 assay, colony formation, xenograft tumor experiments used detect radiosensitivity cells. DNA damage repair proteins, GSH content, intracellular ROS also assayed parental resistant successfully HT29R HCT116R radioresistant after fractionated irradiation, showed significant tolerance further compared with stronger capacity for repair. Meanwhile, ionizing radiation significantly reduced but had no effect on content These results demonstrate that by method continuous Gy. This provides basis exploration mechanism resistance.

Language: Английский

Citations

0
Oral Antioxidant-Engineered Probiotics for the Treatment of Radiation-Induced Colitis DOI
Rong Sun, Shuaiwen Li, Zihui Chen

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Radiation colitis is an inflammatory response induced by damage to colonic tissue from radiation therapy that primarily affects patients undergoing abdominal or pelvic treatments. In this study, we designed a selenium-loaded probiotic (EcN-Se@SA) encapsulated in sodium alginate gel for the oral treatment of colitis. Selenium nanoparticles (Se NPs) exhibit antioxidant, anti-inflammatory, ferroptosis, and repair-promoting properties. To enhance therapeutic efficacy Se NPs radiation-induced colitis, combined with Escherichia coli Nissle 1917 them hydrogel. The resulting EcN-Se@SA formulation not only withstands gastric acid intestinal fluids but also remains colon cecum extended periods. Oral administration attenuates X-ray-induced mice through its antioxidant anti-inflammatory effects, macrophage reprogramming, inhibition ferroptosis histiocytes. This work introduces promising candidate

Language: Английский

Citations

0
Myofibroblasts-targeting Extracellular Vesicles as Drug Delivery for Cardiac Fibrosis Therapy DOI Creative Commons
Yi Wang, Hao Jiang, Qing Chen

et al.

Biomaterials Research, Journal Year: 2025, Volume and Issue: 29

Published: Jan. 1, 2025

Current pharmacological treatments for cardiac fibrosis are often limited by their efficacy and specificity, leading to marked side effects. Fibroblast activation protein (FAP) is specifically expressed on activated myofibroblasts (myoFbs) but not resting fibroblasts, making it a promising target therapy. In this study, we engineered extracellular vesicles (EVs) conjugated with an anti-FAP single-chain variable fragment, termed αFAP-EVs, which myoFbs. Our results demonstrated that αFAP-EVs successfully targeted myoFbs in vitro localized fibrotic regions isoproterenol-induced mouse hearts vivo. To further enhance delivery efficiency, were combined clodronate-loaded liposomes (αFAP-EL@CLD) reduce liver accumulation improve site targeting. αFAP-EL@CLD loaded cholesterol-methylated- phosphorothioate-modified miR-29b (Agomir-29b) or the transforming growth factor beta 1 receptor inhibitor GW788388 significantly inhibited myoFb reduced models. Importantly, these drug-loaded exhibited high therapeutic minimal systemic toxicity, attributed stability capabilities. These findings suggest candidates therapy, offering foundation future clinical applications.

Language: Английский

Citations

0
Investigating the role of disulfidptosis related genes in radiotherapy resistance of lung adenocarcinoma DOI Creative Commons

Xiaoxia Pan,

Hongyan Qian,

Zhouna Sun

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 23, 2024

Background Radiotherapy resistance is an important reason for high mortality in lung cancer patients, but the mechanism still unclear. Dysregulation of cell proliferation and death plays a crucial role onset progression adenocarcinoma (LUAD). In recent times, novel form cellular demise called disulfidptosis, has attracted increasing attention. However, it unclear whether radiation-related disulfidptosis genes have prognostic LUAD. Methods A complete suite bioinformatics tools was used to analyze expression significance genes. Afterward, we investigated predictive risk signature tumor microenvironments (TME), somatic mutations, immunotherapies. addition, conducted series experiments verify differentially expressed radiotherapy related (DERRDGs) vitro . Results total 88 DERRDGs were found. We constructed validated model based on PRELP, FGFBP1, CIITA COL5A1. The enrichment analysis showed DERRDG affected prognosis by influencing (TME) immunotherapy. And nomogram promote clinical application. q-PCR confirmed significant differences between A549 irradiation-resistance A549. Finally, western-blot, IHC staining, small interference experiment suggested that PRELP may be potential biomarker resistance, whose low associated with poor outcomes LUAD patients. Conclusion This study reveals possible underlying mechanisms discovered key gene which helps identify new biomarkers provides basis future research.

Language: Английский

Citations

0