Chemotherapy-Induced Cachexia and Model-Informed Dosing to Preserve Lean Mass in Cancer Treatment DOI Creative Commons
Suzan Farhang‐Sardroodi, Michael A. La Croix, Kathleen P. Wilkie

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Oct. 1, 2021

Abstract Although chemotherapy is a standard treatment for cancer, it comes with significant side effects. In particular, certain agents can induce severe muscle loss, known as cachexia, worsening patient quality of life and outcomes. 5-fluorouracil, an anti-cancer agent used to treat several cancers, has been shown cause loss. Experimental data indicates non-linear dose-dependence loss in mice treated daily or week-day schedules. We present mathematical model chemotherapy-induced wasting that captures this dose-dependence. Area-under-the-curve metrics are proposed quantify the treatment’s effects on lean mass tumour control. Model simulations explore alternate dosing schedules, aging effects, morphine use aim better protecting while actively targeting tumour, ultimately leading improved personalization planning life. Author Summary paper we novel due cancer treatment. Loss relates increased drug toxicity side-effects, decreased survival rates. With our model, examine therapeutic efficacy various schedules controlling growing also preserving mass. Preservation body composition, addition consideration inflammation immune interactions, gut microbiome, other systemic health measures, may lead patient-specific plans improve

Language: Английский

Direct Imaging of Lipid Metabolic Changes in Drosophila Ovary During Aging Using DO-SRS Microscopy DOI Creative Commons
Yajuan Li, Pegah Bagheri,

Phyllis Chang

et al.

Frontiers in Aging, Journal Year: 2022, Volume and Issue: 2

Published: Feb. 3, 2022

Emerging studies have shown that lipids and proteins play versatile roles in various aspects of aging. High-resolution situ optical imaging provides a powerful approach to study the metabolic dynamics during Here, we integrated D2O probing stimulated Raman scattering (DO-SRS) microscopy directly visualize changes aging Drosophila ovary. The subcellular spatial distribution de novo protein synthesis lipogenesis ovary was quantitatively imaged examined. Our spectra showed early stages follicles were protein-enriched whereas mature eggs lipid-enriched. DO-SRS higher earlier developing an increased lipid turned over at late stage. Aged (35 days) flies exhibited dramatic decrease turnover activities both lipids, particularly, germ stem cell niche germarium. We found accumulation unsaturated nurse cells oocytes old flies, suggesting may important role processes oocyte maturation. further detected mitochondrial morphology Cytochrome c To our knowledge, this is first visualizes spatiotemporal metabolism development processes. not only demonstrates application new platform visualizing but also unravels how activity change

Language: Английский

Citations

30
Mitochondrial respiratory quiescence: A new model for examining the role of mitochondrial metabolism in development DOI Creative Commons
Helin Hocaoglu, Matthew Sieber

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 138, P. 94 - 103

Published: April 18, 2022

Language: Английский

Citations

16
Alterations in ether phospholipids metabolism activate the conserved UPR-Xbp1- PDIA3/ERp60 signaling to maintain intestinal homeostasis DOI Creative Commons

Stephanie Makdissi,

Rihab Loudhaief, Smitha George

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111946 - 111946

Published: Feb. 4, 2025

Language: Английский

Citations

0
Optical imaging unveiling metabolic dynamics in cells and organisms during aging and diseases DOI Creative Commons
Lingyan Shi, Jorge Villazon

Med-X, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 20, 2025

Language: Английский

Citations

0
The Critical Balance Between Quiescence and Reactivation of Neural Stem Cells DOI Creative Commons
Adam M. Elkin, Sarah Robbins, Claudia S. Barros

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 672 - 672

Published: May 6, 2025

Neural stem cells (NSC) are multipotent, self-renewing that give rise to all neural cell types within the central nervous system. During adulthood, most NSCs exist in a quiescent state which can be reactivated response metabolic and signalling changes, allowing for long-term continuous neurogenesis injury. Ensuring critical balance between quiescence reactivation is required maintain limited NSC reservoir replenishment throughout lifetime. The precise mechanisms pathways behind this at focus of current research. In review, we highlight discuss recent studies using Drosophila, mammalian zebrafish models contributing understanding molecular underlying NSCs.

Language: Английский

Citations

0
Role of Diet in Stem and Cancer Stem Cells DOI Open Access
Francesca Puca, Monica Fedele,

Debora Rasio

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8108 - 8108

Published: July 23, 2022

Diet and lifestyle factors greatly affect health susceptibility to diseases, including cancer. Stem cells’ functions, their ability divide asymmetrically, set the rules for tissue homeostasis, contribute maintenance, represent entry point of cancer occurrence. cell properties result from complex integration intrinsic, extrinsic, systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem fate determination, lineage specification differentiation. The purpose review is provide comprehensive description multiple “non-metabolic” effects diet little-known such as those liquid-liquid phase separation non-random chromosome segregation (asymmetric division). A deep understanding specific dietetic requirements normal cells may pave way development nutrition-based targeted therapeutic approaches improve regenerative anticancer therapies.

Language: Английский

Citations

13
Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum DOI Creative Commons
Michele R. Plewes, Emilia Przygrodzka,

Corrine F. Monaco

et al.

Life Science Alliance, Journal Year: 2023, Volume and Issue: 6(7), P. e202301968 - e202301968

Published: May 15, 2023

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues therapeutically used for regulating mammalian reproductive cycles blood pressure, inducing term labor, treating ocular disorders. exerts effects via activation of calcium PKC signaling, however, little is known about the cellular events imposed by signaling. Here, we explored early on mitochondrial dynamics mitophagy bovine corpus luteum employing relevant well characterized vivo vitro approaches. We identified PKC/ERK AMPK as critical protein kinases essential fission proteins, DRP1 MFF. Furthermore, report that elicits increased intracellular reactive oxygen species promotes receptor-mediated PINK–Parkin mitophagy. These findings place mitochondrium a novel target response to luteolytic mediator, PGF2α. Understanding processes occurring during luteolysis may serve improving fertility.

Language: Английский

Citations

7
Dual Mode of Mitochondrial ROS Action during Reprogramming to Pluripotency DOI Open Access
Elena V. Skvortsova, Igor Nazarov, Alexey Tomilin

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10924 - 10924

Published: Sept. 18, 2022

Essential changes in cell metabolism and redox signaling occur during the reprogramming of somatic cells into induced pluripotent stem (iPSCs). In this paper, using genetic pharmacological approaches, we have investigated role electron transport chain (ETC) complex-I (CI) mitochondria process to pluripotency. Knockdown NADH-ubiquinone oxidoreductase core subunits S1 (Ndufs1) or subunit B10 (Ndufb10) CI inhibition complex with rotenone mouse embryonic fibroblast (MEF) resulted a significantly decreased number We found that ROS levels due course tightly correlate each other, both reaching peak by day 3 declining 10 process. The transient augmentation mitochondrial reactive oxygen species (ROS) could be attenuated antioxidant treatment, which ameliorated overall reprogramming. However, scavenging after entire was suppressive for iPSC formation. within CI-deficient iPSC-precursors did not improve, but further suppressed Our data therefore point distinct modes action early versus mid late stages substantiate paradigm balanced oxidative phosphorylation maintained on route

Language: Английский

Citations

11
Chemotherapy-induced cachexia and model-informed dosing to preserve lean mass in cancer treatment DOI Creative Commons
Suzan Farhang‐Sardroodi, Michael A. La Croix, Kathleen P. Wilkie

et al.

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(3), P. e1009505 - e1009505

Published: March 21, 2022

Although chemotherapy is a standard treatment for cancer, it comes with significant side effects. In particular, certain agents can induce severe muscle loss, known as cachexia, worsening patient quality of life and outcomes. 5-fluorouracil, an anti-cancer agent used to treat several cancers, has been shown cause loss. Experimental data indicates non-linear dose-dependence loss in mice treated daily or week-day schedules. We present mathematical model chemotherapy-induced wasting that captures this dose-dependence. Area-under-the-curve metrics are proposed quantify the treatment’s effects on lean mass tumour control. Model simulations explore alternate dosing schedules, aging effects, morphine use aim better protecting while actively targeting tumour, ultimately leading improved personalization planning life.

Language: Английский

Citations

8
The critical role of cardiolipin in metazoan differentiation, development, and maturation DOI Open Access

Melissa Olivar‐Villanueva,

Mindong Ren,

Michael Schlame

et al.

Developmental Dynamics, Journal Year: 2023, Volume and Issue: 252(6), P. 691 - 712

Published: Jan. 24, 2023

Cardiolipins are phospholipids that central to proper mitochondrial functioning. Because mitochondria play crucial roles in differentiation, development, and maturation, we would also expect cardiolipin major these processes. Indeed, has been implicated the mechanism of three human diseases affect young infants, implying developmental abnormalities. In this review, will: (1) Review biology cardiolipin; (2) Outline evidence for essential during organismal including embryogenesis cell maturation vertebrate organisms; (3) Place role(s) within larger context development; (4) Suggest avenues future research.

Language: Английский

Citations

3