systemic hypoxia
Recently Published Documents


TOTAL DOCUMENTS

287
(FIVE YEARS 45)

H-INDEX

42
(FIVE YEARS 3)

2022 ◽  
Vol 23 (2) ◽  
pp. 681
Author(s):  
Sara Touhami ◽  
Fanny Béguier ◽  
Tianxiang Yang ◽  
Sébastien Augustin ◽  
Christophe Roubeix ◽  
...  

Hypoxia is potentially one of the essential triggers in the pathogenesis of wet age-related macular degeneration (wetAMD), characterized by choroidal neovascularization (CNV) which is driven by the accumulation of subretinal mononuclear phagocytes (MP) that include monocyte-derived cells. Here we show that systemic hypoxia (10% O2) increased subretinal MP infiltration and inhibited inflammation resolution after laser-induced subretinal injury in vivo. Accordingly, hypoxic (2% O2) human monocytes (Mo) resisted elimination by RPE cells in co-culture. In Mos from hypoxic mice, Thrombospondin 1 mRNA (Thbs1) was most downregulated compared to normoxic animals and hypoxia repressed Thbs-1 expression in human monocytes in vitro. Hypoxic ambient air inhibited MP clearance during the resolution phase of laser-injury in wildtype animals, but had no effect on the exaggerated subretinal MP infiltration observed in normoxic Thbs1−/−-mice. Recombinant Thrombospondin 1 protein (TSP-1) completely reversed the pathogenic effect of hypoxia in Thbs1−/−-mice, and accelerated inflammation resolution and inhibited CNV in wildtype mice. Together, our results demonstrate that systemic hypoxia disturbs TSP-1-dependent subretinal immune suppression and promotes pathogenic subretinal inflammation and can be therapeutically countered by local recombinant TSP-1.


Author(s):  
Grégoire P. Millet ◽  
Martin Burtscher ◽  
Johannes Burtscher

AbstractHypoxia is an essential topic in medical or biological sciences. The main aims of the present study were to examine the most important medical articles (i.e., the top 100 most cited) on hypoxia. We examine how the Nobel-prize awarded hypoxia inducible factor (HIF)-pathway discovery in the early 1990s has changed the thematic composition of this body of literature, with a special emphasis on the studies linking hypoxia and cancer. We searched Pubmed for articles with the terms #Hypox, #Altitude, or #Mountain in the title that have been published in biomedical journals and ranked the articles on their number of citations in Web of Science. A second search was performed in all journals for articles related to hypoxia and cancer. Strikingly, only 12 of the top-100 most-cited articles on hypoxia and only 3 articles of the top-100 articles related to cancer were published before 1995. Moreover, only 5 articles from prior 1995 reached 1000 citations, while 27 articles published in 1995 or later were cited more than 1000 times, most of them on the HIF-1 pathway. Eighty percent of the top-100 articles were related to the HIF pathway, while there were no articles on the application of hypoxia either for therapeutic use (i.e., hypoxic conditioning in patients) or for performance enhancement (i.e., altitude training in athletes). In conclusion, the early-1990s discovery of the HIF pathway and of its molecular regulation has shifted the focus of hypoxia research towards molecular mechanisms and consequences of tissue hypoxia, most notably in cancer. The importance of studies focusing on clinical and performance applications of systemic hypoxia is relatively lower.


2021 ◽  
Vol 6 (1) ◽  
pp. 1266-1274
Author(s):  
Riyadh Firdaus ◽  
Ani Retno Prijanti

Hypoxia inducible factor-1 (HIF-1) is a transcription factor that plays an important role in maintaining oxygen balance at both the cellular and systemic levels, and is associated with various controls in the body. HIF-1 is a heterodimer of alpha and beta subunits. Alpha subunits are mostly dependent on oxygen levels in the body. In many cancers, excessive HIF-1α is thought to be involved in the promotion of tumor growth and metastasis. In addition, in the induction of systemic hypoxia, there is an increase of HIF-1α in the heart, brain, and even the kidneys as an adaptation response to hypoxia. Several studies regarding HIF-1a expression in traumatic brain injury, found that HIF-1a increased immediately after TBI, and decreased significantly after 24 hours. This can be used as a basis for further research on HIF-1a control as an effort to stop tissue damage or even help tissue repair.


2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Matthew D. Martens ◽  
Nivedita Seshadri ◽  
Lucas Nguyen ◽  
Donald Chapman ◽  
Elizabeth S. Henson ◽  
...  

AbstractSystemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for the prostaglandin E1 analog misoprostol during periods of hypoxia, but the mechanisms for this protection are not completely understood. Using a combination of mouse and cell models, we tested if misoprostol is cardioprotective during neonatal hypoxic injury by altering Bnip3 function. Here we report that hypoxia elicits mitochondrial-fragmentation, MPT, reduced ejection fraction, and evidence of necroinflammation, which were abrogated with misoprostol treatment or Bnip3 knockout. Through molecular studies we show that misoprostol leads to PKA-dependent Bnip3 phosphorylation at threonine-181, and subsequent redistribution of Bnip3 from mitochondrial Opa1 and the ER through an interaction with 14-3-3 proteins. Taken together, our results demonstrate a role for Bnip3 phosphorylation in the regulation of cardiomyocyte contractile/metabolic dysfunction, and necroinflammation. Furthermore, we identify a potential pharmacological mechanism to prevent neonatal hypoxic injury.


2021 ◽  
Vol 12 ◽  
Author(s):  
Linda Francistiová ◽  
Adrián Klepe ◽  
Géza Curley ◽  
Károly Gulya ◽  
András Dinnyés ◽  
...  

In December 2019, a new viral disease emerged and quickly spread all around the world. In March 2020, the COVID-19 outbreak was classified as a global pandemic and by June 2021, the number of infected people grew to over 170 million. Along with the patients’ mild-to-severe respiratory symptoms, reports on probable central nervous system (CNS) effects appeared shortly, raising concerns about the possible long-term detrimental effects on human cognition. It remains unresolved whether the neurological symptoms are caused directly by the SARS-CoV-2 infiltration in the brain, indirectly by secondary immune effects of a cytokine storm and antibody overproduction, or as a consequence of systemic hypoxia-mediated microglia activation. In severe COVID-19 cases with impaired lung capacity, hypoxia is an anticipated subsidiary event that can cause progressive and irreversible damage to neurons. To resolve this problem, intensive research is currently ongoing, which seeks to evaluate the SARS-CoV-2 virus’ neuroinvasive potential and the examination of the antibody and autoantibody generation upon infection, as well as the effects of prolonged systemic hypoxia on the CNS. In this review, we summarize the current research on the possible interplay of the SARS-CoV-2 effects on the lung, especially on alveolar macrophages and direct and indirect effects on the brain, with special emphasis on microglia, as a possible culprit of neurological manifestation during COVID-19.


2021 ◽  
Vol 1 (1) ◽  
pp. 47
Author(s):  
Helmi Rizal Helmi ◽  
Grace Madeleine ◽  
David Limanan ◽  
Eny Yulianti ◽  
Frans Ferdinal

Hipoksia adalah suatu kondisi ketika konsentrasi oksigen dalam sel rendah. Kondisi ini dapat meningkatkan pembentukan radikal bebas yang mengarah ke keadaan stres oksidatif yang menghasilkan peroksidasi lipid yang mengakibatkan berbagai kerusakan makromolekul yang dapat merusak otak. Karena itu, tubuh membutuhkan antioksidan untuk mencegah kerusakan tersebut. Salah satu sumber antioksidan eksogen adalah daun Calabash. Penelitian ini bertujuan untuk menentukan kapasitas antioksidan serta konstituen fitokimia daun Berenuk dan menentukan pengaruh ekstrak daun Berenuk dalam menurunkan kadar MDA total dalam darah dan otak tikus Sprague-Dawley yang diinduksi oleh sistemik kronis. hipoksia. Ekstraksi dilakukan dengan metode maserasi menggunakan pelarut etanol. Kapasitas antioksidan dievaluasi dengan uji radikal bebas DPPH. 32 tikus Sprague-Dawley dibagi menjadi 4 kelompok (normoksia, hipoksia 3 hari, 7 hari dan 14 hari (O2 8%; N2 92%)). Setiap kelompok kemudian dibagi lagi menjadi 2 subkelompok (diberikan ekstrak daun dan tidak pemberian). Ekstrak diberikan 400 mg / kg berat badan selama 14 hari. Evaluasi kadar MDA di otak dan darah dilakukan dengan menggunakan metode Wills. Kapasitas Antioksidan Berenuk dengan IC50 = 158,46 μg/mL Semakin lama tikus diinduksi oleh hipoksia sistemik kronis, semakin tinggi kadar MDA dalam darah dan otak. Ada penurunan yang signifikan kadar MDA otak dan darah tikus yang diberi ekstrak daun dibandingkan dengan kelompok yang tidak diberi. Ekstrak Berenuk menurunkan kadar MDA dalam darah dan otak yang disebabkan oleh hipoksia sistemik kronis. Hypoxia is a condition when oxygen concentration in cell is low. This condition can increase free radical formation that leads to oxidative stress state and cause peroxidation of lipid resulting in various macromolecule damages that damage the brain. Thus, the body needs antioxidant to prevent those damage. One of the exogen antioxidant source is calabash leaf. This study aimed to determine the antioxidant capacity as well as the phytochemical constituent of Calabash leaves and determining the effect of Calabash leaves extract in decreasing total MDA levels in the blood and brain of the Sprague-Dawley rats that were induced by chronic systemic hypoxia. Extraction was performed by maceration method using ethanol solvent. Antioxidant capacity was evaluated by DPPH radical scavenging assay. 32 Sprague-Dawley rat were divided into 4 groups (normoxia, 3 days, 7 days and 14 days of hypoxia (O2 8%;N2 92%)). Each group then divided again into 2 subgroups (given leaves extract administration and not). The extract administrated 400 mg/kg body weight for 14 days. The evaluation of MDA levels in the brain and blood was performed by using Wills method. Antioxidant capacity Calabash with IC50 = 158,46 μg/mL The longer the rats were induced by chronic systemic hypoxia, the higher MDA levels in the blood and brain. There was significant decreases in brain and blood MDA levels of rats given leaf compared with the group that was not given. The calabash leaves preventrise of MDA levels in the blood and brain induced by chronic systemic hypoxia


2021 ◽  
Vol 27 ◽  
Author(s):  
Anna Sebestyén ◽  
László Kopper ◽  
Titanilla Dankó ◽  
József Tímár

Cancer hypoxia, recognized as one of the most important hallmarks of cancer, affects gene expression, metabolism and ultimately tumor biology-related processes. Major causes of cancer hypoxia are deficient or inappropriate vascularization and systemic hypoxia of the patient (frequently induced by anemia), leading to a unique form of genetic reprogramming by hypoxia induced transcription factors (HIF). However, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling independently of oxygen supply. The consequences of HIF activation in tumors are the angiogenic phenotype, a novel metabolic profile and the immunosuppressive microenvironment. Cancer hypoxia and the induced adaptation mechanisms are two of the major causes of therapy resistance. Accordingly, it seems inevitable to combine various therapeutic modalities of cancer patients by existing anti-hypoxic agents such as anti-angiogenics, anti-anemia therapies or specific signaling pathway inhibitors. It is evident that there is an unmet need in cancer patients to develop targeted therapies of hypoxia to improve efficacies of various anti-cancer therapeutic modalities. The case has been opened recently due to the approval of the first-in-class HIF2α inhibitor.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0246681
Author(s):  
Louise A. Mesentier-Louro ◽  
Barbara Rangel ◽  
Laurel Stell ◽  
M. Ali Shariati ◽  
Roopa Dalal ◽  
...  

Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1β and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.


Sign in / Sign up

Export Citation Format

Share Document