Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation, fibrosis and CSC development. We used a 4T1-Luc allograft BALB/c syngeneic mouse model and 4T1-Luc and MDA-MB-231 cells for histological analysis, qRT-PCR, western blotting, ROS analysis, mammosphere formation analysis, monolayer fluorescence imaging analysis. Radiotherapy induces TGF-β signaling, oxidative stress markers (4-HNE, NOX2, NOX4, PRDX1, NRF2, HO-1, NQO-1), fibrosis markers (PAI-1, α-SMA, FIBRONECTIN, COL1A1), and CSC properties. However, combination therapy with vactosertib not only inhibits these radiation-induced markers and properties by blocking TGF-β signaling, but also enhances the anticancer effect of radiation by reducing the volume of breast cancer. Therefore, these data suggest that vactosertib can effectively reduce radiation fibrosis and resistance in breast cancer treatment by inhibiting radiation-induced TGF-β signaling and oxidative stress, fibrosis, and CSC.
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http://dx.doi.org/10.1038/s41598-022-20050-9 | DOI Listing |
J Transl Med
December 2024
Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Jiangsu, China.
Background: Coronary artery disease (CAD) has become a dominant economic and health burden worldwide, and the role of autophagy in CAD requires further clarification. In this study, we comprehensively revealed the association between autophagy flux and CAD from multiple hierarchies. We explored autophagy-associated long noncoding RNA (lncRNA) and the mechanisms underlying oxidative stress-induced human coronary artery endothelial cells (HCAECs) injury.
View Article and Find Full Text PDFAnticancer Res
January 2025
Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Background/aim: In a tongue-submandibular lymph node (SLN) metastasis model, the cystine/glutamate transporter solute carrier family 7, member 11 (Slc7a11), also known as xCT, was found to increase in lymphatic endothelial cells (LECs) within SLNs prior to melanoma cell metastasis. However, the precise mechanism by which xCT influences LECs remains unclear. This study aimed to explore the role of xCT in primary cultured LECs.
View Article and Find Full Text PDFDev Neurobiol
January 2025
Neuropharmacology Research Laboratory, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
Owing to the high prevalence of gastrointestinal dysfunction in patients, the gut-brain axis is considered to play a vital role in neurodevelopment diseases. Recent pieces of evidence have pointed to the usage of antibiotics at an early developmental stage to be a causative factor in autism due to its ability to induce critical changes in the gut microbiota. The purpose of the study is to determine the neuroprotective effect of capric acid (CA) on autism in antibiotic-induced gut dysbiosis in rodents.
View Article and Find Full Text PDFBrain Behav
January 2025
Department of General Practice, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, China.
Introduction: Persistent postural-perceptual dizziness (PPPD) is the most prevalent chronic functional dizziness in the clinic. Unsteadiness, dizziness, or non-spinning vertigo are the main symptoms of PPPD, and they are typically aggravated by upright posture, active or passive movement, and visual stimulation. The pathogenesis of PPPD remains incompletely understood, and it cannot be attributed to any specific anatomical defect within the vestibular system.
View Article and Find Full Text PDFExp Neurol
December 2024
Department of Translational Medicine, All India Institute of Medical Sciences (AIIMS)Bhopal, Saket Nagar, Bhopal 462020, Madhya Pradesh, India.
Alzheimer's disease (AD), a diverse neurodegenerative disease, is the leading cause of dementia, accounting for 60-80 % of all cases. The pathophysiology of Alzheimer's disease is unknown, and there is no cure at this time. Recent developments in transcriptome-wide profiling have led to the identification of a number of non-coding RNAs (ncRNAs).
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