Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 22, 2024

Abstract Sepsis, a severe systemic inflammatory response to infection, remains leading cause of morbidity and mortality worldwide. Exosomes, as mediators intercellular communication, play pivotal role in the pathogenesis sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, organ dysfunction. This review highlights emerging significance exosomes these processes. Initially, it provides an in-depth insight into exosome biogenesis characterization, laying groundwork for understanding their diverse intricate functions. Subsequently, explores regulatory roles various cells such neutrophils, macrophages, dendritic cells, T B cells. analysis elucidates how are thus contributing complexity pathophysiology. Additionally, this delves regulation metabolism subsequent dysfunction sepsis. It also establishes connection between coagulation cascade, which affects endothelial integrity promotes thrombogenesis Moreover, discusses dual progression resolution sepsis, exploring complex involvement inflammation healing Furthermore, underscores potential biomarkers therapeutic targets. Understanding mechanisms presents new opportunities novel interventions mitigate outcomes emphasizing promise research critical care settings.

Language: Английский

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Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 28, 2025

Metabolic dysregulation represents one of the major driving forces in aging. Although multiple genetic and pharmacological manipulations are known to extend longevity model organisms, aging is a complex trait, targeting one’s own genes may be insufficient prevent age-dependent deterioration. An alternative strategy could use enzymes from other species reverse age-associated metabolic changes. In this review, we discuss set lower organisms that have been shown affect various parameters linked age-related processes. These include modulators steady-state levels amino acids (METase, ASNase, ADI), NADPH/NADP + and/or reduced form coenzyme Q (CoQH 2 )/CoQ redox potentials (NDI1, AOX, Lb NOX, TPNOX, Ec STH, RquA, LOXCAT, Grubraw, ScURA), GSH (StGshF), mitochondrial membrane potential (mtON mito-dR), or reactive oxygen (DAAO KillerRed-SOD1). We propose leveraging non-mammalian an untapped resource can used delay diseases.

Language: Английский

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Metabolism and HSC fate: what NADPH is made for

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Language: Английский

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Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 671 - 671

Published: Jan. 14, 2025

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011-1012) of new generated daily a healthy young human adult are origin. Therapeutically, HSCs contributed to over 1.5 million transplants (HCTs) globally, making this the most successful regenerative therapy date. We will commence review by briefly highlighting selected key achievements (from 1868 end 20th century) that accomplishment. Much our knowledge hematopoiesis is based on small animal models that, despite their importance, do not always recapitulate hematopoiesis. Given this, we critically progress challenges faced identifying tracing lineage differentiation trajectories, referring murine studies needed. Moving forward given dynamic can readily adjust variety stressors, then discuss recent research advances contributing understanding (i) which HSPCs maintain hematopoiesis, (ii) where these located, (iii) mechanisms come into play when homeostatic switches stress-induced or emergency

Language: Английский

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Metabolic landscape and rewiring in normal hematopoiesis, leukemia and aging

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 111, P. 1 - 15

Published: Feb. 9, 2025

Language: Английский

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Hematopoietic stem cells: Understanding the mechanisms to unleash the therapeutic potential of hematopoietic stem cell transplantation

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 10, 2025

Hematopoietic stem cell transplantation (HSCT) is a promising approach in regenerative medicine and serves as standard treatment for different malignant non-malignant conditions. Despite its widespread applications, HSCT associated with various complications that compromise patients' lives pose considerable risks of morbidity mortality. Understanding the molecular physiology HSCs fundamental to ultimately enhance mobilization, engraftment differentiation HSCs, thus unleashing full therapeutic potential treated patients. This review outlines current understanding HSC biology relevance clinical challenges HSCT. Furthermore, we critically discuss pros cons preclinical murine models exploited field. will unleash derived from induced pluripotent cells (iPSCs) might present an attractive tool which could be preclinically clinically. Nonetheless, further studies are warranted systematically evaluate their terms improving outcome minimizing adverse effects

Language: Английский

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Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

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CD63, a new therapeutical candidate for cholesterol homeostasis regulation through extracellular vesicles?

Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2025, Volume and Issue: 6(1), P. 166 - 70

Published: March 19, 2025

CD63 is a tetraspanin initially associated with late endosomes and contributes to numerous functions at the cell level, such as intracellular endosomal lysosomal trafficking, adhesion, motility. also plays key role in biogenesis release of exosomes, i.e., small extracellular vesicles (EVs) origin, facilitating formation multivesicular bodies (MVBs), coordination sorting complexes required for transport (ESCRT) machinery, selection cargoes carried by future fusion MVBs plasma membrane exosome release. In recent publication Nature Cell Biology , Guillaume van Niel’s team provides arguments favor another EV-linked function CD63, namely regulation cholesterol storage EVs endogenous origin. Complemented two other publications from teams Keisuke Ito Xabier Ostreikoetxea, which respectively describe (i) mitochondrial metabolism on (ii) link between reduced CD63+ dyslipidemia, these highlight homeostasis through exosomes more widely physiological pathological conditions. Future research may thus redefine our approach cellular lipid management therapeutic delivery.

Language: Английский

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Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell include increased fat deposition in bone marrow, impaired stem progenitor (HSPC) function, a propensity towards myeloid differentiation. This shift lineage bias can lead to pre-malignant marrow conditions such as clonal hematopoiesis indeterminate potential (CHIP) or cytopenias undetermined significance (CCUS), frequently setting stage for subsequent development age-related cancers lymphoid lineages. Human also lipid alterations tissues, decreased phospholipid membrane fluidity that arises result saturated fatty acid (FA) accumulation decay n-3 polyunsaturated (PUFA) species by age 80 years, however extent which FA metabolism contributes is less clear. Here, comprehensive multi-omics analyses uncovered role PUFA biosynthesis gene, ELOVL2 , mouse human aging. Whole transcriptome RNA-sequencing studies complementary flow cytometric from aged Elovl2 mutant (enzyme-deficient) mice compared age-matched controls revealed global downregulation markers expression genes involved specifically B development. These unveiled CD79B, vital molecular regulator pro-B pre-B stage, putative surface biomarker whose loss accelerated The lipidome versus wild-type displayed significant biophysical properties cellular membranes. To investigate relevance these finding aging, single RNA-seq dataset HSPCs spectrum rare subpopulation (< 7%) CD34 + expresses healthy adult marrow. HSPC subset, along CD79B -expressing lymphoid-committed cells, were almost completely absent cells isolated elderly samples. Together, findings uncover new roles enzymes regulation function hematopoiesis. In addition, because systemic enzymatic activity resulted are lymphoproliferative neoplasms, this study sheds light on an intriguing pathway could be leveraged future novel therapeutic modality target blood other involving lineage.

Language: Английский

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Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, long-term stability of hematopoietic stem cells (HSCs). Recent research highlights central importance MQC HSC biology, particularly roles mitophagy, biogenesis, fission, fusion transfer regulating function. Mitophagy ensures removal damaged mitochondria, low levels reactive oxygen species (ROS) HSCs, thereby preventing premature aging functional decline. Concurrently, biogenesis adjusts key regulators such as transcription factor A (TFAM) peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring needs HSCs are met. Additionally, transfer, form intercellular material exchange, facilitates mitochondria from bone marrow stromal contributing damage repair support. Although existing studies have revealed significance function, precise molecular mechanisms interactions among different regulatory pathways remain be fully elucidated. Furthermore, potential dysfunction disorders, including its involvement disease progression therapeutic resistance, not yet understood. This review discusses functions under physiological pathological conditions, applications. By summarizing current progress this field, we aim provide insights further development innovative treatment strategies.

Language: Английский

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