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International Journal of Obesity (2005) Dec 2023Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of... (Review)
Review
INTRODUCTION
Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of NAFLD is influenced by repeated intermittent hypoxia, a feature of OSA.
METHODS
This systematic review (SR) investigated CENTRAL, PubMed, and EMBASE databases. The endpoint of this SR was to assess which OSA-related indicators could predict the presence of NAFLD and the effect of bariatric metabolic surgery (BMS) on improving OSA and NAFLD over time.
RESULTS
Compared to previous SRs published in 2013, 14 new publications were added to our SR, alongside studies conducted prior to 2013. The SR ultimately included 28 studies (18 cross-sectional and 10 cohort trials). In the majority of studies, significant correlations were observed between OSA, OSA-related outcomes, and NAFLD. However, the apnea-hypopnea index (AHI) alone proved to be an inadequate predictor of NAFLD. Instead, respiratory and metabolic changes were found to alleviate oxidative stress induced by hypoxemia. Six studies involved patients who underwent BMS, with one evaluating patients before and after BMS, revealing associations between increased OSA and NAFLD improvement following BMS. Six months after surgery, 100% of patients in the mild-to-moderate OSA group were free from fatty liver, and an 89% reduction was observed in the severe OSA group.
CONCLUSION
For the first time, BMS has been tested in treating both OSA and NAFLD pre and postoperative with positive results. Further research, ideally with histological and functional data, is needed to confirm these findings. The SR identified 14 distinct liver outcome tests; however, high heterogeneity and incomplete data precluded a meta-analysis. It is imperative to pay greater attention to the influence of OSA-related factors and uniformity in liver outcomes testing concerning NAFLD. To accomplish this, study designs should be enhanced by incorporating more comprehensive pre- and postoperative evaluations, extending follow-up periods, and employing a more consistent methodology for liver diagnosis in patients with obesity.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cross-Sectional Studies; Obesity; Hypoxia; Chronic Disease; Sleep Apnea, Obstructive
PubMed: 37696927
DOI: 10.1038/s41366-023-01378-2 -
Clinical and Experimental Hypertension... Dec 2024Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an...
BACKGROUND
Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear.
METHODS
PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography.
RESULTS
We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'‑adenosine monophosphate‑activated protein kinase (p‑AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C).
CONCLUSIONS
Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.
Topics: Rats; Animals; AMP-Activated Protein Kinases; Pulmonary Arterial Hypertension; Signal Transduction; Pulmonary Artery; Rats, Sprague-Dawley; Hypoxia; Endoplasmic Reticulum Stress
PubMed: 38527024
DOI: 10.1080/10641963.2024.2332695 -
Medicina Sep 2023Neonatal hypoxic ischemic encephalopathy (HIE) is a type of injury caused by lack of oxygen in the brain during the neonatal period. It is a clinical syndrome clearly... (Review)
Review
Neonatal hypoxic ischemic encephalopathy (HIE) is a type of injury caused by lack of oxygen in the brain during the neonatal period. It is a clinical syndrome clearly recognizable in term and premature newborns secondary to asphyxia at the time of delivery. HIE is estimated to occur at a frequency of 1-3 for each 1000 alive newborns per year in developed countries. In countries of low or medium income, the incidence is up to 10-20 times higher, equivalent to 1-8 alive newborns per each 1000. The social and economic impact has been estimated near US$ 50.2 million per year of life adjusted to disability. At the same time, it is estimated in 7, the number of patients needed to treat with corporal cooling therapy (CCT)to prevent one case of death or severe disability. The etiology is multifactorial and includes prenatal, perinatal and postnatal factors. The diagnosis is based in the inability to support spontaneous breath at the time of delivery requiring assisted ventilation, Apgar less than 5 at 5 and 10 minutes, altered level of consciousness, neonatal reflexes and muscle tone. This article is a review of the stablished and emergent therapeutic strategies based on the pathophysiological disease process.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Hypoxia-Ischemia, Brain; Brain; Consciousness; Hypothermia, Induced
PubMed: 37714119
DOI: No ID Found -
Free Radical Biology & Medicine Nov 2023The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the...
The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in low-oxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure.
Topics: Rats; Animals; RNA, Ribosomal, 16S; Rats, Sprague-Dawley; Hypoxia; Oxidative Stress; Oxygen; Inflammation; Phospholipids
PubMed: 37806597
DOI: 10.1016/j.freeradbiomed.2023.10.002 -
World Journal of Surgical Oncology Jul 2023Intratumoral hypoxia is an essential feature of hepatocellular carcinoma (HCC). Herein, we investigated the hypoxia-based heterogeneity and relevant clinical implication...
OBJECTIVE
Intratumoral hypoxia is an essential feature of hepatocellular carcinoma (HCC). Herein, we investigated the hypoxia-based heterogeneity and relevant clinical implication in HCC.
METHODS
Three HCC cohorts: TCGA-LIHC, LICA-FR, and LIRI-JP were retrospectively gathered. Consensus clustering analysis was utilized for hypoxia-based classification based upon transcriptome of hypoxia genes. Through LASSO algorithm, a hypoxia-relevant prognostic signature was built. Immunotherapeutic response was inferred through analyzing immune checkpoints, T cell inflamed score, TIDE score, and TMB score. RNF145 expression was measured in normoxic or hypoxic HCC cells. In RNF145-knockout cells, CCK-8, TUNEL, and scratch tests were implemented.
RESULTS
HCC patients were classified into two hypoxia subtypes, with more advanced stages and poorer prognosis in cluster2 than cluster1. The heterogeneity in tumor infiltrating immune cells and genetic mutation was found between subtypes. The hypoxia-relevant prognostic model was proposed, composed of ANLN, CBX2, DLGAP5, FBLN2, FTCD, HMOX1, IGLV1-44, IL33, LCAT, LPCAT1, MKI67, PFN2, RNF145, S100A9, and SPP1). It was predicted that high-risk patients presented worse prognosis with an independent and reliable manner. Based upon high expression of immune checkpoints (CD209, CTLA4, HAVCR2, SIRPA, TNFRSF18, TNFRSF4, and TNFRSF9), high T cell inflamed score, low TIDE score and high TMB score, high-risk patients might respond to immunotherapy. Experimental validation showed that RNF145 was upregulated in hypoxic HCC cells, RNF145 knockdown attenuated proliferation and migration, but aggravated apoptosis in HCC cells.
CONCLUSION
Altogether, the hypoxia-based classification and prognostic signature might be useful for prognostication and guiding treatment of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Retrospective Studies; Liver Neoplasms; Hypoxia; Profilins
PubMed: 37481543
DOI: 10.1186/s12957-023-03090-x -
Molecular Oncology Jul 2023Local hypoxia occurs in most solid tumors and is associated with aggressive disease and therapy resistance. Widespread changes in gene expression play a critical role in...
Local hypoxia occurs in most solid tumors and is associated with aggressive disease and therapy resistance. Widespread changes in gene expression play a critical role in the biological response to hypoxia. However, most research has focused on hypoxia-inducible genes as opposed to those that are decreased in hypoxia. We demonstrate that chromatin accessibility is decreased in hypoxia, predominantly at gene promoters and specific pathways are impacted including DNA repair, splicing, and the R-loop interactome. One of the genes with decreased chromatin accessibility in hypoxia was DDX5, encoding the RNA helicase, DDX5, which showed reduced expression in various cancer cell lines in hypoxic conditions, tumor xenografts, and in patient samples with hypoxic tumors. Most interestingly, we found that when DDX5 is rescued in hypoxia, replication stress and R-loop levels accumulate further, demonstrating that hypoxia-mediated repression of DDX5 restricts R-loop accumulation. Together these data support the hypothesis that a critical part of the biological response to hypoxia is the repression of multiple R-loop processing factors; however, as shown for DDX5, their role is specific and distinct.
Topics: Humans; Chromatin; R-Loop Structures; Cell Line; Hypoxia
PubMed: 37013907
DOI: 10.1002/1878-0261.13431 -
International Journal of Molecular... Feb 2024In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory... (Review)
Review
In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory network is critical to the development of hypoxia-tolerant rice varieties and direct seeding of rice. This review summarizes the morphological, physiological, and ecological changes in rice under hypoxia stress, the discovery of hypoxia-tolerant and germination-related genes/QTLs, and the latest research on candidate genes, and explores the linkage of hypoxia tolerance genes and their distribution in indica and japonica rice through population variance analysis and haplotype network analysis. Among the candidate genes, is a typical gene located on the MAPK cascade reaction for indica-japonica divergence; MHZ6 is involved in both the MAPK signaling and phytohormone transduction pathway. has three major haplotypes and one rare haplotype, with Hap3 being dominated by indica rice varieties, and promotes internode elongation in deep-water rice by activating the gene. and Adh1 have similar indica-japonica varietal differentiation, and are mainly present in indica varieties. There are three high-frequency haplotypes of , namely Hap1 (n = 1109), Hap2 (n = 1349), and Hap3 (n = 217); Hap2 is more frequent in japonica, and the genetic background of was derived from the japonica rice subpopulation. Further artificial selection, natural domestication, and other means to identify more resistance mechanisms of this gene may facilitate future research to breed superior rice cultivars. Finally, this study discusses the application of rice hypoxia-tolerant germplasm in future breeding research.
Topics: Oryza; Plant Breeding; Quantitative Trait Loci; Haplotypes; Hypoxia
PubMed: 38396854
DOI: 10.3390/ijms25042177 -
World Journal of Surgical Oncology Aug 2023Currently, there is lack of marker to accurately assess the prognosis of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). This study aims to establish a...
BACKGROUND
Currently, there is lack of marker to accurately assess the prognosis of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). This study aims to establish a hypoxia-related risk scoring model that can effectively predict the prognosis and chemotherapy outcomes of PDAC patients.
METHODS
Using unsupervised consensus clustering algorithms, we comprehensively analyzed The Cancer Genome Atlas (TCGA) data to identify two distinct hypoxia clusters and used the weighted gene co-expression network analysis (WGCNA) to examine gene sets significantly associated with these hypoxia clusters. Then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used to construct a signature and its efficacy was evaluated using the International Cancer Genome Consortium (ICGC) PDAC cohort. Further, the correlation between the risk scores obtained from the signature and carious clinical, pathological, immunophenotype, and immunoinfiltration factors as well as the differences in immunotherapy potential and response to common chemotherapy drugs between high-risk and low-risk groups were evaluated.
RESULTS
From a total of 8 significantly related modules and 4423 genes, 5 hypoxia-related signature genes were identified to construct a risk model. Further analysis revealed that the overall survival rate (OS) of patients in the low-risk group was significantly higher than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk scoring signature was an independent factor for prognosis prediction. Analysis of immunocyte infiltration and immunophenotype showed that the immune score and the anticancer immune response in the high-risk were significantly lower than that in the low-risk group.
CONCLUSION
The constructed hypoxia-associated prognostic signature demonstrated could be used as a potential risk classifier for PDAC.
Topics: Humans; Prognosis; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Hypoxia
PubMed: 37605192
DOI: 10.1186/s12957-023-03142-2 -
Journal of Nanobiotechnology Nov 2023Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal...
Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal cells-derived small extracellular vesicles (MSC-sEVs) have shown therapeutic value in various ocular disorders. Recent studies have revealed that hypoxic preconditioning can improve the effectiveness of MSC-sEVs in tissue regeneration. However, whether hypoxic preconditioned MSC-sEVs (Hyp-sEVs) exert superior effects on photoreceptor protection relative to normoxic conditioned MSC-sEVs (Nor-sEVs) remains unclear. Here, we reported that Hyp-sEVs further improved retinal structure, recovered retinal function, and suppressed photoreceptor apoptosis in N-methyl-N-nitrosourea (MNU)-induced mouse model compared with Nor-sEVs. Hyp-sEVs also exhibited enhanced anti-apoptotic roles in MNU-provoked 661 W cell injury in vitro. We then analyzed the protein profiles of Nor-sEVs and Hyp-sEVs by LC-MS/MS and found that growth-associated protein 43 (GAP43) was enriched in Hyp-sEVs. The knockdown of GAP43 abolished the retinal therapeutic effects of Hyp-sEVs. Mechanistically, hypoxic stimulation-induced hypoxia-inducible factor-1α (HIF-1α) activation was responsible for preventing tripartite motif-containing protein 25 (TRIM25)-mediated GAP43 ubiquitination and degradation, leading to the upregulation of GAP43 in Hyp-sEVs. Together, our findings uncover the efficacy and mechanism of Hyp-sEVs-based photoreceptor protection and highlight the potential of Hyp-sEVs as optimized therapeutics for retinal degeneration.
Topics: Mice; Animals; Retinal Degeneration; Chromatography, Liquid; Tandem Mass Spectrometry; Retina; Extracellular Vesicles; Hypoxia
PubMed: 38001463
DOI: 10.1186/s12951-023-02225-2 -
BMC Medicine Jan 2024We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS).
METHODS
This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms.
RESULTS
The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07-0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO 18.1 ~ 20.8 mmol/L) and improved SpO (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS.
CONCLUSIONS
The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05023941.
Topics: Humans; Altitude Sickness; Acetazolamide; Prospective Studies; Acute Disease; Hypoxia; Ischemic Preconditioning
PubMed: 38166913
DOI: 10.1186/s12916-023-03209-7