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Journal of Controlled Release :... Nov 2023Extracellular vesicles (EVs) play a pivotal role in intercellular communication and have been implicated in cancer progression. Hypoxia, a pervasive hallmark of cancer,... (Review)
Review
Extracellular vesicles (EVs) play a pivotal role in intercellular communication and have been implicated in cancer progression. Hypoxia, a pervasive hallmark of cancer, is known to regulate EV biogenesis and function. Hypoxic EVs contain a specific set of proteins, nucleic acids, lipids, and metabolites, capable of reprogramming the biology and fate of recipient cells. Enhancing the intrinsic therapeutic efficacy of EVs can be achieved by strategically modifying their structure and contents. Moreover, the use of EVs as drug delivery vehicles holds great promise for cancer treatment. However, various hurdles must be overcome to enable their clinical application as cancer therapeutics. In this review, we aim to discuss the current knowledge on the hypoxic regulation of EVs. Additionally, we will describe the underlying mechanisms by which EVs contribute to cancer progression in hypoxia and outline the progress and limitations of hypoxia-related EV therapeutics for cancer.
Topics: Humans; Extracellular Vesicles; Neoplasms; Cell Communication; Drug Delivery Systems; Hypoxia
PubMed: 37739015
DOI: 10.1016/j.jconrel.2023.09.034 -
JAMA Apr 2024
Topics: Humans; COVID-19; Oxygen; Oxygen Inhalation Therapy; Hypoxia; Clinical Trials as Topic
PubMed: 38501210
DOI: 10.1001/jama.2024.2935 -
Advanced Healthcare Materials Aug 2023Hypoxia is a typical feature of most solid tumors and has important effects on tumor cells' proliferation, invasion, and metastasis. This is the key factor that leads to... (Review)
Review
Hypoxia is a typical feature of most solid tumors and has important effects on tumor cells' proliferation, invasion, and metastasis. This is the key factor that leads to poor efficacy of different kinds of therapy including chemotherapy, radiotherapy, photodynamic therapy, etc. In recent years, the construction of hypoxia-relieving functional nanoplatforms through nanotechnology has become a new strategy to reverse the current situation of tumor microenvironment hypoxia and improve the effectiveness of tumor treatment. Here, the main strategies and recent progress in constructing nanoplatforms are focused on to directly carry oxygen, generate oxygen in situ, inhibit mitochondrial respiration, and enhance blood perfusion to alleviate tumor hypoxia. The advantages and disadvantages of these nanoplatforms are compared. Meanwhile, nanoplatforms based on organic and inorganic substances are also summarized and classified. Through the comprehensive overview, it is hoped that the summary of these nanoplatforms for alleviating hypoxia could provide new enlightenment and prospects for the construction of nanomaterials in this field.
Topics: Humans; Tumor Hypoxia; Neoplasms; Photochemotherapy; Oxygen; Hypoxia; Tumor Microenvironment; Cell Line, Tumor; Photosensitizing Agents
PubMed: 37055912
DOI: 10.1002/adhm.202300089 -
Stem Cell Research & Therapy Jul 2023Mesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular...
BACKGROUND
Mesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular vesicles (EVs). Accordingly, EVs are being pursued as a promising alternative to cell-based therapies. Menstrual blood-derived stromal cells (MenSCs) are a type of MSC that, due to their immunomodulatory and regenerative properties, have emerged as an innovative source. Additionally, new strategies of cell priming may potentially alter the concentration and cargo of released EVs, leading to modification of their biological properties. In this study, we aimed to characterize the EVs released by MenSCs and compare their therapeutic potential under three different preconditioning conditions (proinflammatory stimuli, physioxia, and acute hypoxia).
METHODS
MenSCs were isolated from five healthy women. Following culturing to 80% confluence, MenSCs were exposed to different priming conditions: basal (21% O), proinflammatory stimuli (IFNγ and TNFα, 21% O), physioxia (1-2% O), and acute hypoxia (< 1% O) for 48-72 h. Conditioned media from MenSCs was collected after 48 h and EVs were isolated by a combination of ultra-filtration and differential centrifugation. An extensive characterization ranging from nano-flow cytometry (nFC) to quantitative high-throughput shotgun proteomics was performed. Bioinformatics analyses were used to derive hypotheses on their biological properties.
RESULTS
No differences in the morphology, size, or number of EVs released were detected between priming conditions. The proteome analysis associated with basal MenSC-EVs prominently revealed their immunomodulatory and regenerative capabilities. Furthermore, quantitative proteomic analysis of differentially produced MenSC-EVs provided sufficient evidence for the utility of the differential preconditioning in purpose-tailoring EVs for their therapeutic application: proinflammatory priming enhanced the anti-inflammatory, regenerative and immunomodulatory capacity in the innate response of EVs, physioxia priming also improves tissue regeneration, angiogenesis and their immunomodulatory capacity targeting on the adaptive response, while acute hypoxia priming, increased hemostasis and apoptotic processes regulation in MenSC-EVs, also by stimulating immunomodulation mainly through the adaptive response.
CONCLUSIONS
Priming of MenSCs under proinflammatory and hypoxic conditions affected the cargo proteome of EVs released, resulting in different therapeutic potential, and thus warrants experimental exploration with the aim to generate better-defined MSC-derived bioproducts.
Topics: Humans; Female; Proteomics; Proteome; Extracellular Vesicles; Mesenchymal Stem Cells; Hypoxia
PubMed: 37507751
DOI: 10.1186/s13287-023-03413-5 -
Molecular Pharmaceutics Jul 2023Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue... (Review)
Review
Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue regeneration. However, hypoxia, a common occurrence in the wound bed, can impede normal healing processes. To enhance wound healing, oxygenation strategies that could effectively increase wound oxygen levels are effective. The present review summarizes wound healing stages and the role of hypoxia in wound healing and overviews current strategies to incorporate various oxygen delivery or generating materials for wound dressing, including catalase, nanoenzyme, hemoglobin, calcium peroxide, or perfluorocarbon-based materials, in addition to photosynthetic bacteria and hyperbaric oxygen therapy. Mechanism of action, oxygenation efficacy, and potential benefits and drawbacks of these dressings are also discussed. We conclude by highlighting the importance of design optimization in wound dressings to address the clinical needs to improve clinical outcomes.
Topics: Humans; Wound Healing; Bandages; Skin; Oxygen; Hypoxia
PubMed: 37338289
DOI: 10.1021/acs.molpharmaceut.3c00352 -
Circulation. Arrhythmia and... Sep 2023Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (K) modulation during hypoxia has not been explored. We investigated the...
BACKGROUND
Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (K) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of K pore-forming subunits.
METHODS
Whole heart K RNA expression was probed. Whole-cell K current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout (6.2-gKO) murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed.
RESULTS
Expression patterns were essentially identical for all K subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor subunit) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, 6.2-gKO atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both K knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in 6.2-gKO hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen.
CONCLUSIONS
K block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia.
Topics: Humans; Animals; Mice; KATP Channels; Atrial Fibrillation; Tolbutamide; Tachycardia; Heart Atria; Hypoxia; Adenosine Triphosphate
PubMed: 37646176
DOI: 10.1161/CIRCEP.123.011870 -
Marine Pollution Bulletin Sep 2023Hypoxia is a harmful result of anthropogenic climate change. With the expansion of global low-oxygen zones (LOZs), many organisms have faced unprecedented challenges... (Review)
Review
Hypoxia is a harmful result of anthropogenic climate change. With the expansion of global low-oxygen zones (LOZs), many organisms have faced unprecedented challenges affecting their survival and reproduction. Extensive research has indicated that oxygen limitation has drastic effects on aquatic animals, including on their development, morphology, behavior, reproduction, and physiological metabolism. In this review, the global distribution and formation of LOZs were analyzed, and the impacts of hypoxia on aquatic animals and the molecular responses of aquatic animals to hypoxia were then summarized. The commonalities and specificities of the response to hypoxia in aquatic animals in different LOZs were discussed lastly. In general, this review will deepen the knowledge of the impacts of hypoxia on aquaculture and provide more information and research directions for the development of fishery resource protection strategies.
Topics: Animals; Ecosystem; Aquaculture; Hypoxia; Climate Change; Oxygen
PubMed: 37453286
DOI: 10.1016/j.marpolbul.2023.115207 -
Plant Signaling & Behavior Dec 2023Hypoxia triggers reactive oxygen species (ROS)-induced elevation in cytoplasmic calcium (Ca) in the plant cells. Calcium-dependent protein kinase 12 (CPK12) acts as a...
Hypoxia triggers reactive oxygen species (ROS)-induced elevation in cytoplasmic calcium (Ca) in the plant cells. Calcium-dependent protein kinase 12 (CPK12) acts as a sensor to recognize the Ca signature and is activated by autophosphorylation. Then, the CPK12 moves into the nucleus with the help of phosphatidic acid (PA) and phosphorylates ERF-VII family proteins that activate hypoxia signaling and response. The study provides a novel mechanism of hypoxia signaling in plants. Moreover, the mechanism of hypoxia-specific Ca signature generation remains elusive.
Topics: Protein Kinases; Hypoxia; Cell Hypoxia; Phosphorylation; Calcium; Reactive Oxygen Species
PubMed: 37875477
DOI: 10.1080/15592324.2023.2273593 -
Chinese Journal of Natural Medicines Jul 2023Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache,... (Review)
Review
Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.
Topics: Humans; Biological Products; Hypoxia; Reactive Oxygen Species; Adenosine Triphosphate; Alkaloids
PubMed: 37517818
DOI: 10.1016/S1875-5364(23)60410-8 -
Biomedicine & Pharmacotherapy =... Aug 2023Pulmonary arterial hypertension (PAH) is a chronic obstructive disease characterized by vascular remodeling. Studies have confirmed that ginsenoside Rg1 can improve...
Pulmonary arterial hypertension (PAH) is a chronic obstructive disease characterized by vascular remodeling. Studies have confirmed that ginsenoside Rg1 can improve pulmonary hypertension to a certain extent, but the potential mechanism by which it improves hypoxia-induced PAH remains unclear. The aim of this study was to investigate the therapeutic effect of ginsenoside Rg1 on hypoxia-induced PAH. The results showed that hypoxia promoted inflammation, EndMT, and vascular remodeling, which were accompanied by decreased CCN1 levels and increased p-NFκB p65, TGF-β1, and p-Smad 2/3 levels. Treatment with ginsenoside Rg1, recombinant CCN1, BAY-11-7082, and SB-431542 could prevent hypoxia-induced vascular remodeling, reduce the expression of the hypoxia-induced inflammatory cytokines TNF-α and IL-1β, inhibit the expression of the mesenchymal markers α-SMA and Vimentin and restore the expression of the endothelial markers CD31 and VE-cadherin to improve hypoxia-induced EndMT, which may be associated with the upregulation of CCN1 protein expression and downregulation of p-NFκB p65, TGF-β1, and p-Smad 2/3 in rats and cells. siRNA CCN1 transfection increased the expression of p-NFκB p65, TGF-β1, and p-Smad 2/3 and accelerated the occurrence and development of inflammation and EndMT after hypoxia. In summary, our study indicated that hypoxia-induced EndMT and inflammation play a role in hypoxic pulmonary hypertension (HPH). Ginsenoside Rg1 treatment could reverse hypoxia-induced EndMT and inflammation by regulating CCN1 and has potential value in the prevention and treatment of HPH.
Topics: Rats; Animals; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Transforming Growth Factor beta1; Vascular Remodeling; Inflammation; Hypoxia
PubMed: 37216706
DOI: 10.1016/j.biopha.2023.114920