Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis DOI Creative Commons
Jun Sun,

Qiuhua Zeng,

Zhimin Wu

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Abstract Background Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate effects underlying mechanisms of SCs-Exos on INRV following PNI. Results found that GW4869 inhibited INRV, as well normoxic (N-SCs-Exos) exhibited significant pro-INRV vivo vitro were potentiated by hypoxic (H-SCs-Exos). Upregulation glycolysis emerged a pivotal factor for after PNI, evidenced observation 3PO administration, glycolytic inhibitor, process vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, gene expression while simultaneously suppressing acetyl-CoA production pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) than N-SCs-Exos Furthermore, we determined enriched with miR-21-5p N-SCs-Exos. Knockdown attenuated pro-glycolysis H-SCs-Exos. Mechanistically, orchestrated EC metabolism favor targeting von Hippel-Lindau/hypoxia-inducible factor-1α PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated inhibiting PDH-E1α-mediated oxidative phosphorylation. Conclusion This study unveiled novel intrinsic mechanism providing promising therapeutic target post-injury regeneration repair. Graphical

Language: Английский

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions DOI Creative Commons
Zhou Chen,

Fangfang Han,

Yan Du

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

Citations

539
Living microecological hydrogels for wound healing DOI Creative Commons
Guopu Chen, Fengyuan Wang, Xiaoxuan Zhang

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(21)

Published: May 24, 2023

Chronic hard-to-heal wounds draw great attention worldwide, as their treatments are limited by infections and hypoxia. Inspired the natural oxygen production capacity of algae competitive advantage beneficial bacteria over other microbes, we presented a living microecological hydrogel (LMH) with functionalized Chlorella Bacillus subtilis encapsulation to realize continuous delivery anti-infections for promoting chronic wound healing. As consisted thermosensitive Pluronic F-127 wet-adhesive polydopamine, LMH could keep liquid at low temperature while quickly solidifying tightly adhering bed. It was demonstrated that optimizing proportion encapsulated microorganism, continuously produce relieve hypoxia support proliferation B. , eliminate colonized pathogenic bacteria. Thus, substantially promoted healing infected diabetic wounds. These features make valuable practical clinical applications.

Language: Английский

Citations

101
Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges DOI Creative Commons

Mengnan Cheng,

Yujia Jiang, Jiangshan Xu

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2023, Volume and Issue: 50(9), P. 625 - 640

Published: March 27, 2023

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology, from the invention of microscope 350 years ago recent emergence single-cell sequencing, which scientific community has been able visualize at an unprecedented resolution. Most recently, Spatially Resolved Transcriptomics (SRT) technologies have filled gap probing spatial or even three-dimensional organization molecular foundation behind mysteries life, including origin different cellular populations developed totipotent cells human diseases. In this review, we introduce progress challenges on SRT perspectives bioinformatic tools, as well representative applications. With currently fast-moving promising results early adopted research projects, can foresee bright future such new tools understanding most profound analytical level.

Language: Английский

Citations

76
A tissue injury sensing and repair pathway distinct from host pathogen defense DOI Creative Commons
Siqi Liu,

Yun Ha Hur,

Xin Cai

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(10), P. 2127 - 2143.e22

Published: April 24, 2023

Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after independent of microbiome or adaptive immunity. Moreover, Il24 ablation mice impedes not only epidermal proliferation re-epithelialization but also capillary fibroblast regeneration within the dermal wound bed. Conversely, ectopic IL-24 induction homeostatic epidermis triggers global epithelial-mesenchymal repair responses. Mechanistically, expression depends upon both IL24-receptor/STAT3 signaling hypoxia-stabilized HIF1α, which converge following trigger autocrine paracrine involving IL-24-mediated receptor metabolic regulation. Thus, parallel innate immune sensing pathogens resolve infections, stem cells sense signals orchestrate repair.

Language: Английский

Citations

62
Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing DOI Creative Commons
Anastasia du Halgouet, Aurélie Darbois,

Mansour Alkobtawi

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(1), P. 78 - 92.e6

Published: Jan. 1, 2023

Tissue repair processes maintain proper organ function following mechanical or infection-related damage. In addition to antibacterial properties, mucosal associated invariant T (MAIT) cells express a tissue transcriptomic program and promote skin wound healing when expanded. Herein, we use human-like mouse model of full-thickness excision assess the underlying mechanisms MAIT cell function. Single-cell RNA sequencing analysis suggested that already at steady state. Following excision, promoted keratinocyte proliferation, thereby accelerating healing. Using grafts, parabiosis, adoptive transfer experiments, show migrated into in receptor (TCR)-independent but CXCR6 chemokine receptor-dependent manner. Amphiregulin secreted by Expression was probably independent sustained TCR stimulation. Overall, our study provides mechanistic insights skin.

Language: Английский

Citations

54
Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems DOI
Rochelle Castillo, Ikjot Sidhu, Igor Dolgalev

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(84)

Published: June 2, 2023

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context systemic impact remain poorly understood. We thus profiled psoriasis (PsO) as a prototypic immune-mediated condition with high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses 25 healthy, active lesion, clinically uninvolved biopsies integration public single-cell data revealed marked differences in immune microniches between healthy inflamed skin. Tissue-scale cartography further identified core disease across all lesions, including emergence an suprabasal epidermal state presence B lymphocytes lesional Both distal nonlesional samples were stratified by severity not disease. This segregation was driven macrophage-, fibroblast-, lymphatic-enriched spatial regions gene signatures associated metabolic dysfunction. Together, these findings suggest that mild severe forms PsO have distinct may profoundly alter composition unaffected sites. In addition, our study provides valuable resource research community to organization

Language: Английский

Citations

46
3D printing of personalized magnesium composite bone tissue engineering scaffold for bone and angiogenesis regeneration DOI
Wenzhao Wang, Ling Wang, Boqing Zhang

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 484, P. 149444 - 149444

Published: Feb. 9, 2024

Language: Английский

Citations

22
Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span DOI Open Access
Joshua I. Gray, Daniel P. Caron, Steven B. Wells

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(96)

Published: June 7, 2024

During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role humans has largely been defined blood. Here, we analyzed phenotype, transcriptome, function, repertoire of human blood mucosal lymphoid 176 donors across life span, revealing distinct profiles children compared with adults. In early life, clonally diverse Vδ1 subsets predominate tissues, comprising naïve differentiated effector tissue repair functions, whereas cytolytic Vδ2 populate blood, spleen, lungs. With age, exhibit clonal expansions elevated signatures, which are disseminated sites. adults, enriched express residency profiles. Thus, antigenic exposures over childhood drive evolution compartmentalization cells, leading to age-dependent roles

Language: Английский

Citations

19
Metabolic coordination between skin epithelium and type 17 immunity sustains chronic skin inflammation DOI
Ipsita Subudhi, Piotr Konieczny, Aleksandr Prystupa

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1665 - 1680.e7

Published: May 20, 2024

Language: Английский

Citations

18
Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB DOI

Yunjin Lee,

Tomoe Ishikawa, Hyeseung Lee

et al.

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

Published: April 1, 2025

Language: Английский

Citations

3