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Redox Biology May 2024Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal... (Review)
Review
Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to the production of HIF-1α, which plays an indispensable role in a series of physiological activities, such as menstruation and metamorphosis. The sensitive regulation of HIF-1α maintains the cellular viability and regenerative capacity of the endometrium against cellular stresses induced by hypoxia and excess reactive oxygen species. In contrast, abnormal HIF-1α levels exacerbate the development of various endometrial pathologies. This knowledge opens important possibilities for the development of promising HIF-1α-centered strategies to ameliorate endometrial disease. Nonetheless, additional efforts are required to elucidate the regulatory network of endometrial HIF-1α and promote the applications of HIF-1α-centered strategies in the human endometrium. Here, we summarize the role of the HIF-1α-mediated pathway in endometrial physiology and pathology, highlight the latest HIF-1α-centered strategies for treating endometrial diseases, and improve endometrial receptivity.
PubMed: 38815332
DOI: 10.1016/j.redox.2024.103205 -
PloS One 2024To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory... (Comparative Study)
Comparative Study
OBJECTIVE
To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs.
METHODS
A prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI.
RESULTS
A total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p<0.001) was observed. The OSI cut-off value for predicting an OI of >15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05).
CONCLUSION
The findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.
Topics: Humans; Infant, Newborn; Respiration, Artificial; Respiratory Insufficiency; Male; Female; Prospective Studies; Oxygen Saturation; Hypoxia; Oxygen; Intensive Care Units, Neonatal; Infant, Premature; ROC Curve
PubMed: 38814919
DOI: 10.1371/journal.pone.0304278 -
Saudi Journal of Gastroenterology :... May 2024The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute hypoxic respiratory failure. However, limited evidence exists...
High-flow nasal cannula oxygen therapy is equally effective to noninvasive ventilation for mild-moderate acute respiratory distress syndrome in patients with acute pancreatitis: A single-center, retrospective cohort study.
BACKGROUND
The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute hypoxic respiratory failure. However, limited evidence exists regarding the effectiveness of HFNC for acute respiratory distress syndrome (ARDS) in patients with acute pancreatitis (AP).
METHODS
This retrospective analysis focused on AP patients with mild-moderate ARDS, who were treated with either HFNC or noninvasive ventilation (NIV) in the emergency medicine department, from January 2020 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation or a switch to any other study treatment (NIV for patients in the NFNC group and vice versa).
RESULTS
A total of 146 patients with AP (68 in the HFNC group and 78 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 17.6% and 19.2% in the NIV group - a risk difference of -1.6% (95% CI, -11.3 to 14.0%; P = 0.806). The most common causes of failure in the HFNC group were aggravation of respiratory distress and hypoxemia. However, in the NIV group, the most common reasons for failure were treatment intolerance and exacerbation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (16.7% vs 60.0%, 95% CI -66.8 to -6.2; P = 0.023). Multivariate logistic regression analysis showed that body mass index (≥28), acute physiology and chronic health evaluation II score (≥15), partial arterial oxygen tension/fraction of inspired oxygen (≤200), and respiratory rate (≥32/min) at 1 hour were independent predictors of HFNC failure.
CONCLUSION
In AP patients with mild-moderate ARDS, the usage of HFNC did not lead to a higher rate of treatment failure when compared to NIV. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.
PubMed: 38813712
DOI: 10.4103/sjg.sjg_24_24 -
Turkish Journal of Medical Sciences 2023Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with...
BACKGROUND/AIM
Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with proven efficacy, the morbidity and mortality rates remain high. The aim of this study was to neurodevelopmentally evaluate patients who underwent therapeutic hypothermia.
MATERIAL AND METHOD
Included herein were patients who underwent hypothermia between 2018 and 2020. Their medical files were reviewed retrospectively, and their demographic and clinical information was recorded. Patients whose contact information was available were called to the developmental pediatrics outpatient clinic for a neurodevelopmental evaluation. The Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) was used as the evaluation tool. Laboratory values and clinical parameters of the patients were further analyzed.
RESULTS
It was found that 42 patients underwent hypothermia in 3 years, of whom 14 (33.3%) had died. Of the 28 patients who were discharged, 20 children could be reached, and a neurodevelopmental evaluation was performed. Developmental delay in the cognitive area was detected in 11 (55%) patients, delay in the language area was found in 9 (45%) patients, and delay in the motor area was found in 11 (55%) patients. The correlation and regression analysis results determined that the time to start cooling was the most effective common factor in all 3 fields of scoring.
CONCLUSION
The time to start cooling is related to the neurodevelopmental outcomes of patients with HIE. The earlier cooling is started, the better the neurodevelopmental results. Despite therapeutic hypothermia, the neurodevelopmental development of infants may be adversely affected. These patients should be followed-up neurodevelopmentally for a long time.
Topics: Humans; Hypoxia-Ischemia, Brain; Hypothermia, Induced; Male; Female; Infant, Newborn; Retrospective Studies; Neurodevelopmental Disorders; Infant; Child, Preschool; Developmental Disabilities
PubMed: 38813516
DOI: 10.55730/1300-0144.5748 -
Heliyon May 2024Cancer remains a major global health concern, necessitating the development of novel therapeutic approaches. Hypoxia is a common characteristic of solid tumors that...
Cancer remains a major global health concern, necessitating the development of novel therapeutic approaches. Hypoxia is a common characteristic of solid tumors that plays a critical role in tumor progression, making it a prime target for anticancer therapies. This study aimed to determine the effects of copper oxide nanoparticles (CuONPs) on human gastrointestinal cancer cells in hypoxic condition for the first time. Toxicity of CuONPs was evaluated on human colon and gastric adenocarcinoma cells and normal fibroblasts by alamarBlue assay. Real-time polymerase chain reaction (PCR) was performed to study the effects of CuONPs on genes involved in cell apoptosis. To elucidate the molecular mechanisms underlying the effects of CuONPs in hypoxic condition, molecular docking was conducted on HIF-1α. Results revealed dose- and cell-type-dependent toxic effects of CuONPs, as a more significant ( < 0.0001) decrease in viability of LoVo cells (23 %) was observed compared to MKN-45 and HDF cells. In addition, CuONPs significantly ( < 0.0001) reduced LoVo cell viability down to 30.2 % in hypoxic condition. Gene expression analysis revealed significant ( < 0.0001) overexpression of and but downregulation of and after treatment with CuONPs. Molecular docking indicated the preferable binding of CuONPs to the HIF-1α PAS-B domain through interaction with 15 residues with -4.8 kcal/mol binding energy. Our findings open up new possibilities for modulating HIF-1 activity and inhibiting hypoxia-induced tumor progression.
PubMed: 38813193
DOI: 10.1016/j.heliyon.2024.e31414 -
Turkish Journal of Medical Sciences 2023A significant cause of mortality and morbidity in the neonatal era is hypoxic-ischemic encephalopathy (HIE). This study examined the histopathological analysis and...
BACKGROUND/AIM
A significant cause of mortality and morbidity in the neonatal era is hypoxic-ischemic encephalopathy (HIE). This study examined the histopathological analysis and neuroprotective impact of syringin (SYR) in an experimental HIE rat model.
MATERIAL AND METHODS
On the 7th postnatal day, 24 Wistar albino rats were evaluated in 3 groups using the HIE model under gas anesthesia. In the experiment, Group A received 10 mg/kg SYR plus dimethyl sulfoxide (DMSO), Group B received DMSO only, and Group C served as a sham group. Immunohistochemical techniques were used to assess apoptotic cell measurement and proinflammatory cytokines (TNF-α and IL-1β primary antibodies).
RESULTS
Rats suffering from hypoxic-ischemic brain damage had their apoptosis assessed. The SYR and sham groups had statistically fewer cells undergoing apoptosis (p < 0.001). There was no difference between the groups in terms of IL-1β and TNF-α during immunohistochemical staining. Neuronal degeneration was significantly lower in the histological evaluation of the hippocampus in the SYR group (p = 0.01). A statistically significant difference (p = 0.01) was observed between the SYR and the control groups regarding pericellular and perivascular edema.
CONCLUSION
SYR reduced apoptosis, perivascular and pericellular edema, and neuronal degeneration in rat cerebral tissue. These results raise the possibility that SYR may have a neuroprotective effect on the harm brought on by HIE. This is the first investigation of SYR's function within the HIE paradigm.
Topics: Animals; Neuroprotective Agents; Hypoxia-Ischemia, Brain; Rats; Rats, Wistar; Disease Models, Animal; Animals, Newborn; Phenylpropionates; Glucosides; Apoptosis; Interleukin-1beta
PubMed: 38813032
DOI: 10.55730/1300-0144.5697 -
Nature and Science of Sleep 2024Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its...
BACKGROUND
Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations.
METHODS
Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing.
RESULTS
DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p<0.0167), and significant alterations in the microbial structure (p=0.014), notably the order , accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with (p=0.0008) and (p=0.0019), while body weight was linked to (p=0.0377). Additionally, the abundance of was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339).
CONCLUSION
IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.
PubMed: 38812701
DOI: 10.2147/NSS.S454297 -
Endoscopy International Open May 2024Sedation of high-risk patients is a relevant issue in interventional endoscopy. This is especially because standard oximetric monitors display only hypoxia and not the...
Sedation of high-risk patients is a relevant issue in interventional endoscopy. This is especially because standard oximetric monitors display only hypoxia and not the preceding hypercapnia. Therefore, the question arises whether use of a nasal positive airway pressure (nPAP) system can decrease the rate of sedation-associated events. A randomized, prospective trial was conducted at University Hospital Ulm, including 98 consecutive patients, identified as high-risk (American Society of Anesthesiologists physical status ≥3) and scheduled for prolonged (>15 minutes) endoscopic procedures. Patients underwent 1:1 randomization to two groups: interventional (nPAP-Mask) and control (conventional oxygen supplementation). Levels of CO were measured noninvasively by transcutaneous capnometry device. The primary outcome was incidence of hypoxia (SpO <90% over 10 seconds) and incidence of severe hypoxia was incidence of SpO <80% over 10 seconds. One of our secondary objectives was to determine if the nPAP-Mask could result in significant CO retention among high-risk patients. Data analysis showed lower incidence of hypoxia in the interventional group (10/47 vs. 31/251) <0.05. Episodes of severe hypoxia (SpO <80% over 10 seconds) were more frequent in the control group (8/51) compared with the intervention group (2/47) <0.05. There was no significant difference in ΔCO levels in the interventional vs. control group (-6.01±7.66 vs. -7.35±8.59 mm Hg). In high-risk patients use of a nasal positive airway pressure system could significantly lower risk of hypoxia, especially in prolonged procedures. The nPAP-Mask does not induce CO retention when compared with conventional oxygen supplementation.
PubMed: 38812697
DOI: 10.1055/a-2306-9144 -
Turkish Journal of Medical Sciences 2024To investigate the roles of vascular endothelial growth inhibitor (VEGI) and hypoxia-inducible factor-1α (HIF-1α) in the treatment of refractory interstitial...
BACKGROUND/AIM
To investigate the roles of vascular endothelial growth inhibitor (VEGI) and hypoxia-inducible factor-1α (HIF-1α) in the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS) with hyperbaric oxygen (HBO).
MATERIALS AND METHODS
A total of 38 patients were included. They were assessed before and 6 months after HBO treatment. Three-day voiding diaries were recorded, and O'leary-Sant scores, visual analog scale (VAS) scores, quality of life (QoL) scores, pelvic pain, and urgency/frequency (PUF) scores were evaluated. Bladder capacity was assessed by cystoscopy. Bladder mucosa was collected for Western blot, qRT-PCR, and immunofluorescence staining to compare the expression of VEGI and HIF-1α before and after treatment.
RESULTS
Compared with before treatment, patients showed significant improvements in 24-h voiding frequency (15.32 ± 5.38 times), nocturia (3.71 ± 1.80 times), O'leary-Sant score (20.45 ± 5.62 points), VAS score (41.76 ± 17.88 points), QoL score (3.03 ± 1.44 points), and PUF score (19.95 ± 6.46 points) after treatment (p < 0.05). There was no significant difference in bladder capacity before and after treatment (p ≥ 0.05). The expression levels of VEGI and HIF-1α protein and mRNA were significantly decreased 6 months after treatment compared with before treatment. Immunofluorescence staining results showed that the double positive expression of VEGI and HIF-1α protein in bladder tissue of IC/BPS patients after HBO treatment quantitatively decreased significantly.
CONCLUSION
This study identified a possible mechanism by which VEGI and HIF-1α expression decreased after HBO treatment due to hypoxia reversal, which improved symptoms in IC/BPS patients.
Topics: Humans; Hyperbaric Oxygenation; Hypoxia-Inducible Factor 1, alpha Subunit; Female; Middle Aged; Male; Cystitis, Interstitial; Adult; Quality of Life; Urinary Bladder; Aged; Treatment Outcome
PubMed: 38812622
DOI: 10.55730/1300-0144.5762 -
Turkish Journal of Medical Sciences 2024Proinflammatory chemokines have been shown to play crucial roles in implantation, spiral artery invasion, and the fetomaternal immunological response. In this context,...
BACKGROUND/AIM
Proinflammatory chemokines have been shown to play crucial roles in implantation, spiral artery invasion, and the fetomaternal immunological response. In this context, we investigated the levels of fractalkine (CX3CL1) and chemokine CC motif ligand 4 (CCL4 or MIP-1β) in maternal serum and amniotic fluids in pregnant women with intrauterine growth restriction (IUGR).
MATERIALS AND METHODS
This prospective cohort study was carried out at Fırat University Obstetrics Clinic between January 1, 2022 and July 1, 2022. Group (G) 1: The control group consisted of 40 pregnant women who underwent elective cesarean section (CS) at 38-40 weeks of gestation. G2: A total of 40 pregnant women with IUGR at 28-37 weeks of gestation were included in the study group. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), hypoxia-inducible factor-1 alpha (HIF-1α), macrophage inflammatory protein-1 beta (MIP-1β), and fractalkine were measured in maternal serum and amniotic fluid samples obtained during CS.
RESULTS
When maternal age was compared, no statistically significant difference was observed between G1 and G2 (p = 0.374). The number of gravidity was found to be statistically higher in G1 compared to G2 (p = 0.003). The mean gestational week was statistically higher in G1 (p < 0.001). Maternal serum MIP-1β (p = 0.03) and IFN-γ (p = 0.006) levels were higher in G1. The birth weight of the baby (p < 0.001) and umbilical cord blood gas pH value (p < 0.001) at birth were higher in G1. HIF-1α (p < 0.001), fractalkine (p < 0.001), MIP-1β (p < 0.001), TNF-α (p = 0.007), IL-1β (p < 0.001), and IFN-γ levels (p = 0.007) in amniotic fluid were higher in G2.
CONCLUSION
Elevated levels of proinflammatory factors, including fractalkine and MIP-1β, along with inflammatory factors such as TNF-α, IL-1β, and IFN-γ, as well as increased HIF-1α levels in amniotic fluid, are associated with intrauterine growth restriction (IUGR) attributed to a hypoxic amniotic environment.
Topics: Humans; Female; Chemokine CX3CL1; Amniotic Fluid; Pregnancy; Prospective Studies; Fetal Growth Retardation; Adult; Chemokine CCL4
PubMed: 38812616
DOI: 10.55730/1300-0144.5789