Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium DOI Creative Commons
Wanchao Chen, Yang Wang, Jiancheng Zheng

et al.

Burns & Trauma, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 1, 2023

Abstract Background Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation is progressive ulceration, which results in the expansion nonirradiated area refractory wounds. Current theories cannot explain progression ulcers. Cellular senescence refers as irreversible growth arrest that occurs stress, contributes tissue dysfunction by inducing paracrine senescence, stem cell chronic inflammation. However, it not yet clear how cellular facilitates continuous Here, we aim investigate role promoting indicate potential therapeutic strategy for Methods ulcer animal models were established local 40 Gy X-ray continuously evaluated >260 days. roles assessed using pathological analysis, molecular detection RNA sequencing. Then, effects conditioned medium from human umbilical cord mesenchymal cells (uMSC-CM) investigated models. Results with features clinical patients primary mechanisms responsible We have characterized being closely associated found exogenous transplantation senescent significantly aggravated them. Mechanistic studies sequencing suggested radiation-induced secretions facilitating Finally, uMSC-CM was effective mitigating inhibiting senescence. Conclusions Our findings only characterize but also their treatment.

Language: Английский

Mechanistic approach of the inhibitory effect of chrysin on inflammatory and apoptotic events implicated in radiation-induced premature ovarian failure: Emphasis on TGF-β/MAPKs signaling pathway DOI Creative Commons
Eman M. Mantawy,

Riham S. Said,

Amal Kamal Abdel‐Aziz

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2018, Volume and Issue: 109, P. 293 - 303

Published: Nov. 3, 2018

Radiotherapy is one of the most relevant treatment modalities for various types malignancies. However, it causes premature ovarian failure (POF) and subsequent infertility in women reproductive age; hence urging development effective radioprotective agents. Chrysin, a natural flavone, possesses several pharmacological activities owing to its antioxidant, anti-inflammatory anti-apoptotic properties. Therefore, aim this study was investigate efficacy chrysin limiting γ-radiation-mediated POF elucidate underlying molecular mechanisms. Immature female Sprague-Dawley rats were subjected single dose γ-radiation (3.2 Gy) and/or treated with (50 mg/kg) once daily two weeks before three days post-irradiation. Chrysin prevented radiation-induced dysfunction by restoring estradiol levels, preserving normal histoarchitecture combating follicular loss. Eelectron microscopic analysis showed that disruption ultrastructure components due radiation exposure hampered administration. Mechanistically, chrsyin able reduce levels inflammatory markers NF-κB, TNF-α, iNOS COX-2 damage. also exhibited potent effects against cell death downregulating expression cytochrome c caspase 3. Radiation obviously induced upregulation TGF-β protein phospholyration activation downstream mitogen-activated kinases (MAPKs); p38 JNK. Notably, administration successfully counteracted these effects. These findings revealed may be beneficial ameliorating POF, predominantly via TGF-β/MAPK signaling pathways leading subsequently hindering apoptotic signal transduction implicated POF.

Language: Английский

Citations

56
Redox Imbalance in Intestinal Fibrosis: Beware of the TGFβ-1, ROS, and Nrf2 Connection DOI
Giovanni Latella

Digestive Diseases and Sciences, Journal Year: 2017, Volume and Issue: 63(2), P. 312 - 320

Published: Dec. 22, 2017

Language: Английский

Citations

54
Sirtuin 3 is essential for hypertension‐induced cardiac fibrosis via mediating pericyte transition DOI Creative Commons
Han Su,

Heng Zeng,

Bo Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2020, Volume and Issue: 24(14), P. 8057 - 8068

Published: May 28, 2020

Hypertension is the key factor for development of cardiac fibrosis and diastolic dysfunction. Our previous study showed that knockout sirtuin 3 (SIRT3) resulted in dysfunction mice. In present study, we explored role SIRT3 angiotensin II (Ang-II)-induced pericyte-myofibroblast transition. NG2 tracing reporter NG2-DsRed mouse was crossed with wild-type (WT) mice SIRT3KO Cardiac function, reactive oxygen species (ROS) were measured. Mice infused Ang-II 28 days a significant reduction expression hearts. Knockout sensitized Ang-II-induced elevation isovolumic relaxation time (IVRT) ejection fraction (EF) fractional shortening (FS). fibrosis, capillary rarefaction hypertrophy further enhanced by SIRT3. pericyte had significantly increased number heart. increase pericytes. To examine pericyte-myofibroblast/fibroblast transition, DsRed pericytes co-stained FSP-1 α-SMA. infusion led to numbers DsRed+ /FSP-1+ /α-SMA+ cells, while developed addition, promoted NADPH oxidase-derived ROS formation together transforming growth beta 1 (TGF-β1). We concluded induced partly mechanisms involving SIRT3-mediated transition ROS-TGF-β1 pathway.

Language: Английский

Citations

44
Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling DOI Creative Commons
Yimin Sun, Bingyan Liu, Jianping Xie

et al.

Molecular Medicine Reports, Journal Year: 2022, Volume and Issue: 25(5)

Published: March 23, 2022

Aspirin reduces the liver fibrosis index and inflammation in patients rats. However, specific mechanism underlying effects of aspirin are yet to be elucidated. The present study aimed investigate on thioacetamide (TAA)‑induced rats hepatic stellate cells (HSCs) via TGF‑β1/Smad signaling pathway. Liver was induced Sprague Dawley by intraperitoneal injection 200 mg/kg TAA twice weekly for 8 weeks. (30 mg/kg) administered gavage once every morning over a period Masson's trichrome H&E staining were used detect analyze pathological changes tissues. Western blot analysis immunohistochemistry applied determine protein expression levels α‑smooth muscle actin (α‑SMA), collagen I, TGF‑β1, phosphorylated (p)‑Smad2 p‑Smad3. In addition, reverse transcription‑quantitative PCR performed mRNA α‑SMA, type I α 1 chain (COL1A1) TGF‑β1. results demonstrated that treatment with significantly reduced serum alanine aminotransferase, aspartate aminotransferase hydroxyproline + compared group. rat model, tissues improved following aspirin. Similarly, marked decrease observed p‑Smad2 Furthermore, administration decreased COL1A1 HSCs treated different concentrations (10, 20 40 mmol/l), p‑Smad3 dose‑dependent manner. Overall, showed attenuated production suppressing pathway, thus revealing potential fibrosis.

Language: Английский

Citations

28
Characterization of cellular senescence in radiation ulcers and therapeutic effects of mesenchymal stem cell-derived conditioned medium DOI Creative Commons
Wanchao Chen, Yang Wang, Jiancheng Zheng

et al.

Burns & Trauma, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 1, 2023

Abstract Background Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation is progressive ulceration, which results in the expansion nonirradiated area refractory wounds. Current theories cannot explain progression ulcers. Cellular senescence refers as irreversible growth arrest that occurs stress, contributes tissue dysfunction by inducing paracrine senescence, stem cell chronic inflammation. However, it not yet clear how cellular facilitates continuous Here, we aim investigate role promoting indicate potential therapeutic strategy for Methods ulcer animal models were established local 40 Gy X-ray continuously evaluated >260 days. roles assessed using pathological analysis, molecular detection RNA sequencing. Then, effects conditioned medium from human umbilical cord mesenchymal cells (uMSC-CM) investigated models. Results with features clinical patients primary mechanisms responsible We have characterized being closely associated found exogenous transplantation senescent significantly aggravated them. Mechanistic studies sequencing suggested radiation-induced secretions facilitating Finally, uMSC-CM was effective mitigating inhibiting senescence. Conclusions Our findings only characterize but also their treatment.

Language: Английский

Citations

14