Development of a cell‐free strategy to recover aged skeletal muscle after disuse DOI Open Access
Yu‐Fu Wu, Eduardo A. De La Toba, Svyatoslav Dvoretskiy

et al.

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 601(22), P. 5011 - 5031

Published: March 23, 2022

Extended periods of bed rest and limb immobilization are required for healing post-injury or disease, yet disuse can result in significant muscle atrophy decreased quality life older adults. Physical rehabilitation is commonly prescribed to recover these deficits, accumulation reactive oxygen species sustained rates protein degradation persist during the period that significantly delay prevent recovery. Pericytes, considered primary mesenchymal vascular stromal cell skeletal muscle, secrete beneficial factors maintain baseline mass, minimal information exists regarding pericyte response In current study, single-cell RNA sequencing functional assays were performed demonstrate pericytes mouse lose capacity synthesize antioxidants This was used guide design a strategy which healthy donor stimulated with hydrogen peroxide (H

Language: Английский

A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo DOI Creative Commons
Longchuan Bai, Haibin Zhou,

Renqi Xu

et al.

Cancer Cell, Journal Year: 2019, Volume and Issue: 36(5), P. 498 - 511.e17

Published: Nov. 1, 2019

Language: Английский

Citations

492
Tissue Stem Cells: Architects of Their Niches DOI Creative Commons
Elaine Fuchs, Helen M. Blau

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(4), P. 532 - 556

Published: Oct. 1, 2020

Language: Английский

Citations

231
Mitochondrial dysfunction: roles in skeletal muscle atrophy DOI Creative Commons
Xin Chen, Yanan Ji, Ruiqi Liu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 26, 2023

Abstract Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, damage to mitochondria can lead a series of pathophysiological changes. Mitochondrial dysfunction atrophy, its molecular mechanism leading atrophy is complex. Understanding the pathogenesis mitochondrial useful for prevention treatment finding drugs methods target modulate function are urgent tasks atrophy. In this review, we first discussed normal muscle. Importantly, described effect on mechanisms involved. Furthermore, regulatory different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 NF-κB pathways, etc.) factors were investigated dysfunction. Next, analyzed manifestations caused by diseases. Finally, summarized preventive therapeutic effects targeted regulation including drug therapy, exercise diet, gene stem cell therapy physical therapy. This review great significance holistic understanding role muscle, which helpful researchers further has an inspiring development strategies targeting future.

Language: Английский

Citations

114
Cancer cachexia: molecular mechanisms and treatment strategies DOI Creative Commons
Tania Setiawan, Ita Novita Sari, Yoseph Toni Wijaya

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: May 22, 2023

Abstract Muscle wasting is a consequence of physiological changes or pathology characterized by increased catabolic activity that leads to progressive loss skeletal muscle mass and strength. Numerous diseases, including cancer, organ failure, infection, aging-associated are associated with wasting. Cancer cachexia multifactorial syndrome mass, without the fat resulting in functional impairment reduced quality life. It caused upregulation systemic inflammation stimuli, leading inhibition protein synthesis enhancement catabolism. Here, we summarize complex molecular networks regulate function. Moreover, describe multi-organ roles cancer cachexia. Although one main causes cancer-related deaths, there still no approved drugs for Thus, compiled recent ongoing pre-clinical clinical trials further discussed potential therapeutic approaches

Language: Английский

Citations

103
STAT3 and STAT5 Activation in Solid Cancers DOI Open Access
Sebastian Igelmann, Heidi A. Neubauer, Gerardo Ferbeyre

et al.

Cancers, Journal Year: 2019, Volume and Issue: 11(10), P. 1428 - 1428

Published: Sept. 25, 2019

The Signal Transducer and Activator of Transcription (STAT)3 5 proteins are activated by many cytokine receptors to regulate specific gene expression mitochondrial functions. Their role in cancer is largely context-dependent as they can both act oncogenes tumor suppressors. We review here the STAT3/5 activation solid cancers summarize their association with survival patients. molecular mechanisms that underpin oncogenic activity signaling include regulation genes control cell cycle death. However, recent advances also highlight critical target mediating inflammation stemness. In addition, STAT3 functions required for transformation. On other hand, several suppressor pathways on or signaling, including tyrosine phosphatases, sumo ligase Protein Inhibitor Activated (PIAS3), E3 ubiquitin TATA Element Modulatory Factor/Androgen Receptor-Coactivator 160 kDa (TMF/ARA160), miRNAs miR-124 miR-1181, alternative reading frame 19 (p19ARF)/p53 pathway Suppressor Cytokine Signaling 1 3 (SOCS1/3) proteins. Cancer mutations epigenetic alterations may alter balance between pro-oncogenic activities associated explaining progression human animal models.

Language: Английский

Citations

87
Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation DOI Creative Commons
Alessandra Dall’Agnese, Luca Caputo, Chiara Nicoletti

et al.

Molecular Cell, Journal Year: 2019, Volume and Issue: 76(3), P. 453 - 472.e8

Published: Sept. 10, 2019

Language: Английский

Citations

79
The jam session between muscle stem cells and the extracellular matrix in the tissue microenvironment DOI Creative Commons

Mafalda Loreti,

Alessandra Sacco

npj Regenerative Medicine, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 17, 2022

Skeletal muscle requires a highly orchestrated coordination between multiple cell types and their microenvironment to exert its function maintain homeostasis regenerative capacity. Over the past decades, significant advances, including lineage tracing single-cell RNA sequencing, have contributed identifying resident populations participating in maintenance repair. Among these populations, stem cells (MuSC), also known as satellite cells, response stress or injury, are able proliferate, fuse, form new myofibers repair damaged tissue. These reside adjacent myofiber surrounded by specific complex microenvironment, niche. Major components of niche extracellular matrix (ECM) proteins, instruct MuSC behavior. However, during aging muscle-associated diseases, progressively loses ability, part due dysregulation ECM components. This review provides an overview composition importance microenvironment. We discuss relevant proteins how mutations impact young aged tissue contribute diseases. Recent discoveries improved our knowledge about skeletal muscle, which has helped mimic architecture capacity MuSC. Further understanding extrinsic signals from controlling innovative technologies still required develop therapies improve

Language: Английский

Citations

57
Autophagy in muscle regeneration: potential therapies for myopathies DOI
Wei Chen, Yushi Chen, Yuxi Liu

et al.

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2022, Volume and Issue: 13(3), P. 1673 - 1685

Published: April 17, 2022

Language: Английский

Citations

50
FAM3A plays a key role in protecting against tubular cell pyroptosis and acute kidney injury DOI Creative Commons
Xiaolong Li,

Feifei Yuan,

Yabing Xiong

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 74, P. 103225 - 103225

Published: June 8, 2024

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death tubular epithelial cells has been reported to accelerate a variety of AKI, the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression related ATP depletion renal cells. We found FAM3A, mitochondrial protein assists synthesis, decreased negatively correlated both mice patients AKI. Knockout FAM3A worsened function decline, increased macrophage neutrophil infiltration, facilitated ischemia/reperfusion model. Conversely, overexpression alleviated pyroptosis, inhibited ischemic Mechanistically, promoted PI3K/AKT/NRF2 signaling, thus blocking reactive oxygen species (mt-ROS) accumulation. NLRP3 inflammasome sensed overload mt-ROS then activated Caspase-1, which cleaved GSDMD, pro-IL-1β, pro-IL-18 into their mature forms mediate pyroptosis. Of interest, NRF2 activator pro-pyroptotic effects depletion, whereas deletion blocked anti-pyroptotic FAM3A. Thus, our study provides new demonstrates potential target treating

Language: Английский

Citations

10
Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions DOI Creative Commons
Tiantian Wang, Dong Zhou, Zhen Hong

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract Sarcopenia is defined as a muscle‐wasting syndrome that occurs with accelerated aging, while cachexia severe wasting associated conditions such cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. can considered component of cachexia, the bidirectional interplay between adipose tissue skeletal muscle potentially serving molecular mechanism for both conditions. However, underlying mechanisms differ. Recognizing distinctions these disorders essential advancing basic translational research in this area, enhancing diagnostic accuracy ultimately achieving effective therapeutic solutions affected patients. This review discusses microenvironment's changes contributing to conditions, recent approaches like lifestyle modifications, small molecules, interventions, emerging strategies gene editing, stem cell therapy, gut microbiome modulation. We also address challenges opportunities multimodal aiming provide insights into pathogenesis sarcopenia aiding innovative strategy development improved treatments.

Language: Английский

Citations

1