Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial design DOI
Alistaire D. Ruggiero, Ravichandra Vemuri,

Megan Blawas

et al.

GeroScience, Journal Year: 2023, Volume and Issue: 45(5), P. 2785 - 2803

Published: June 1, 2023

Language: Английский

MiR‐17‐5p‐engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21 DOI Creative Commons
Wei Qian,

Jianlong Su,

Sheng Meng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 29, 2024

Abstract Delayed wound healing is a major complication of diabetes, and associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports microRNA expression in small extracellular vesicles (sEVs), miR‐17‐5p‐engineered sEVs (sEVs 17‐OE ) encapsulated them gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment fabricated. SEVs successfully fabricated 16‐fold increase miR‐17‐5p expression. inhibited senescence promoted proliferation, migration, tube formation high glucose‐induced human umbilical vein endothelial cells (HG‐HUVECs). Additionally, also performs promotive effect dermal fibroblasts (HG‐HDFs). Mechanism analysis showed expressions p21 phosphatase tensin homolog (PTEN), as target genes miR‐17‐5p, downregulated significantly by . Accordingly, downstream pathways PTEN, activated. Next, loaded GelMA to fabricate novel bioactive dressing evaluate their effects healing. Gel‐sEVs effectively accelerated promoting angiogenesis collagen deposition. The mechanism may be local cell proliferation. Therefore, loading hydrogel, offering an option chronic management

Language: Английский

Citations

26

Macrophage senescence in health and diseases DOI Creative Commons

Longling Wang,

Wenxiang Hong,

Hong Zhu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(4), P. 1508 - 1524

Published: Jan. 20, 2024

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence macrophages may lead to maladaptation, immune dysfunction, finally development age-related diseases, infections, autoimmune malignancies. However, it is a ubiquitous, multi-factorial, dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair embryogenesis. In this review, we summarize some general molecular changes several specific biomarkers during macrophage which bring new sight recognize senescent different conditions. Also, take an in-depth look at functional macrophages, metabolism, autophagy, polarization, phagocytosis, antigen presentation, infiltration or recruitment. Furthermore, degenerations diseases associated with as well mechanisms relevant genetic regulations are integrated, not only emphasizing possibility regulating benefit age-associated but implication on finding potential targets drugs clinically.

Language: Английский

Citations

21

Cellular senescence of renal tubular epithelial cells in acute kidney injury DOI Creative Commons
Juan Chen,

Huhai Zhang,

Xiangling Yi

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 5, 2024

Abstract Cellular senescence represents an irreversible state of cell-cycle arrest during which cells secrete senescence-associated secretory phenotypes, including inflammatory factors and chemokines. Additionally, these exhibit apoptotic resistance phenotype. serves a pivotal role not only in embryonic development, tissue regeneration, tumor suppression but also the pathogenesis age-related degenerative diseases, malignancies, metabolic kidney diseases. The renal tubular epithelial (RTEC) constitutes critical cellular event progression acute injury (AKI). RTEC inhibits regeneration repair processes and, concurrently, promotes transition AKI to chronic disease via mechanisms underlying are multifaceted include telomere shortening or damage, DNA mitochondrial autophagy deficiency, disorders, endoplasmic reticulum stress, epigenetic regulation. Strategies aimed at inhibiting senescence, targeting clearance senescent RTEC, promoting apoptosis hold promise for enhancing prognosis AKI. This review primarily focuses on characteristics impact intervening AKI, aiming provide foundation understanding providing potentially effective approaches treatment.

Language: Английский

Citations

20

Cell senescence in liver diseases: pathological mechanism and theranostic opportunity DOI
David Sanfeliu-Redondo, Albert Gibert‐Ramos, Jordi Gracia‐Sancho

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(7), P. 477 - 492

Published: March 14, 2024

Language: Английский

Citations

19

The Role of Oxidative Stress in Tumorigenesis and Progression DOI Creative Commons
Kexin Li,

Zhangyuzi Deng,

Chunran Lei

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 441 - 441

Published: March 2, 2024

Oxidative stress refers to the imbalance between production of reactive oxygen species (ROS) and endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, series diseases has been demonstrated. Advances carcinogenic research have revealed oxidative as a pivotal pathophysiological pathway tumorigenesis be involved lung cancer, glioma, hepatocellular carcinoma, leukemia, so on. This review combs effects on each phase fate determination, three features are discussed. takes part processes ranging from tumor death via pathways like mitochondrial stress, endoplasmic reticulum ferroptosis. It can affect by engaging complex relationships death, cancer. The influence progression is multi-stage interlaced process that includes two aspects promotion inhibition, with mitochondria core regulation. A deeper more comprehensive understanding conducive exploring therapies.

Language: Английский

Citations

18

ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence DOI
Zhangyang Qi, Weiqi Yang,

Baibing Xue

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(9), P. 2000 - 2016

Published: May 18, 2024

Bleomycin exhibits effective chemotherapeutic activity against multiple types of tumors, and also induces various side effects, such as pulmonary fibrosis neuronal defects, which limit the clinical application this drug. Macroautophagy/autophagy has been recently reported to be involved in functions bleomycin, yet mechanisms their crosstalk remain insufficiently understood. Here, we demonstrated that reactive oxygen species (ROS) produced during bleomycin activation hampered autophagy flux by inducing lysosomal membrane permeabilization (LMP) obstructing degradation. Exhaustion ROS with N-acetylcysteine relieved LMP defects. Notably, observed blockage preceded emergence cellular senescence treatment. In addition, promoting or inhibiting autophagy-lysosome degradation alleviated exacerbated phenotypes senescence, respectively. This suggests alternation is more a regulatory mechanism than consequence bleomycin-induced senescence. Taken together, reveal specific role mediating defects autophagic further regulating vitro vivo. Our findings, conversely, indicate pathway target for modulating bleomycin. These provide new perspective optimizing clinically applicable chemotherapeutics devoid severe side-effects.

Language: Английский

Citations

18

Pathological mechanisms of kidney disease in ageing DOI
Takeshi Yamamoto, Yoshitaka Isaka

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(9), P. 603 - 615

Published: July 18, 2024

Language: Английский

Citations

18

Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth DOI
Zahra Dashti, Zeynab Yousefi,

Pouria Kiani

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 154, P. 155811 - 155811

Published: Feb. 2, 2024

Language: Английский

Citations

16

Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells DOI Creative Commons
Youkun Bi, Xinlong Qiao, Zhaokui Cai

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

4

Role of the Extracellular Matrix in Cancer: Insights into Tumor Progression and Therapy DOI Creative Commons
Nimeet Desai, Deepak Kumar Sahel,

Bhakti Kubal

et al.

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

Published: Jan. 6, 2025

Abstract The extracellular matrix (ECM) serves not only as a structural scaffold but also an active regulator of cancer progression, profoundly influencing tumor behaviour and the microenvironment (TME). This review focuses into pivotal role ECM alterations in facilitating metastasis explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis disrupt associated signalling pathways critical for architecture cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods suppress synthesis enzymatic degrade it, thereby mitigating tumor‐promoting effects. discussion extends innovative modulating stiffness, focusing on roles cancer‐associated fibroblasts lysyl oxidases, which key contributors remodelling mechanical signalling. By strategically modifying components, aim enhance efficacy existing treatments, tackle resistance mechanisms, achieve more durable outcomes. Insights from recent studies clinical trials highlight promise overcoming treatment improving patient Advancing our understanding biology leads development effective therapies.

Language: Английский

Citations

2