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Redox Biology May 2024Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to...
Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to cysteine. As glutathione redox is important in muscle regeneration in aging, we hypothesized that xCT exerts upstream control over skeletal muscle glutathione redox, metabolism and regeneration. Bioinformatic analyses of publicly available datasets revealed that expression levels of xCT and GSH-related genes are inversely correlated with myogenic differentiation genes. Muscle satellite cells (MuSCs) isolated from Slc7a11 mice, which harbour a mutation in the Slc7a11 gene encoding xCT, required media supplementation with 2-mercaptoethanol to support cell proliferation but not myotube differentiation, despite persistently lower GSH. Slc7a11 primary myotubes were larger compared to WT myotubes, and also exhibited higher glucose uptake and cellular oxidative capacities. Immunostaining of myogenic markers (Pax7, MyoD, and myogenin) in cardiotoxin-damaged tibialis anterior muscle fibres revealed greater MuSC activation and commitment to differentiation in Slc7a11 muscle compared to WT mice, culminating in larger myofiber cross-sectional areas at 21 days post-injury. Slc7a11 mice subjected to a 5-week exercise training protocol demonstrated enhanced insulin tolerance compared to WT mice, but blunted muscle mitochondrial biogenesis and respiration in response to exercise training. Our results demonstrate that the absence of xCT inhibits cell proliferation but promotes myotube differentiation by regulating cellular metabolism and glutathione redox. Altogether, these results support the notion that myogenesis is a redox-regulated process and may help inform novel therapeutic approaches for muscle wasting and dysfunction in aging and disease.
PubMed: 38815331
DOI: 10.1016/j.redox.2024.103213 -
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 -
The Turkish Journal of Pediatrics May 2024Acute respiratory failure is a prevalent condition in childhood with a high rate of mortality. Invasive mechanical ventilation support may be required for the management...
BACKGROUND
Acute respiratory failure is a prevalent condition in childhood with a high rate of mortality. Invasive mechanical ventilation support may be required for the management of these patients. Extracorporeal membrane oxygenation (ECMO) is a method used when ventilation support is insufficient. However, the less invasive extracorporeal carbon dioxide removal method can be used as an alternative in cases of hypercapnic respiratory failure.
CASE
A 9-year-old patient with cystic fibrosis presented to the hospital with acute respiratory failure due to pneumonia. Bilateral patchy areas of consolidation were evident in the chest x-ray. Invasive mechanical ventilation support was consequently provided to treat severe hypercapnia. Although peak and plateau pressure levels exceeded 32 cmH₂O (49 cmH₂O) and 28 cmH₂O (35 cmH₂O), respectively, the patient continued to have severe respiratory acidosis. Therefore extracorporeal carbon dioxide removal support was initiated to provide lung-protective ventilation. By Day 10, venovenous ECMO support was initiated due to deteriorating oxygenation.
CONCLUSION
In cases where conventional invasive mechanical ventilation support is insufficient due to acute hypercapnic respiratory failure, extracorporeal carbon dioxide removal support, which is less invasive compared to ECMO, should be considered as an effective and reliable alternative method. However, it should be noted that extracorporeal carbon dioxide removal support does not affect oxygenation; it functions solely as a carbon dioxide removal system.
Topics: Humans; Cystic Fibrosis; Respiratory Insufficiency; Extracorporeal Membrane Oxygenation; Hypercapnia; Child; Carbon Dioxide; Male; Acute Disease; Respiration, Artificial
PubMed: 38814300
DOI: 10.24953/turkjpediatr.2024.4588 -
Turkish Journal of Medical Sciences 2023The percentage change in the stroke volume index (SVI) due to the mini fluid challenge (MFC) (MFC-ΔSVI%) is used commonly in daily practice. However, up to 20% of... (Observational Study)
Observational Study
BACKGROUND/AIM
The percentage change in the stroke volume index (SVI) due to the mini fluid challenge (MFC) (MFC-ΔSVI%) is used commonly in daily practice. However, up to 20% of patients remain in the gray zone of this variable. Thus, it was aimed to compare the MFC-ΔSVI% and the percentage change in the cardiac power index (CPI) due to the MFC (MFC-ΔCPI%) with the baseline values of the pulse pressure variation (PPV) and stroke volume variation (SVV) in terms of their abilities to predict fluid responsiveness.
MATERIALS AND METHODS
The SVI, CPI, SVV, and PPV were recorded before 100 mL of isotonic saline was infused (MFC), after MFC was completed, and after an additional 400 mL of isotonic saline was infused to complete 500 mL of fluid loading (FL). Patients whose SVI increased more than 15% after the FL were defined as fluid responders.
RESULTS
Sixty-seven patients completed the study and 35 (52%) of them were responders.The areas under the receiver operating characteristics curves for the MFC-ΔSVI% and MFC-ΔCPI% (0.94; 95% CI: 0.86-0.99 and 0.89; 95% CI: 0.79-0.95, respectively) were significantly higher than those for the SVV and PPV (0.63; 95% CI: 0.50-0.75 and 0.55; 95% CI: 0.42-0.67, respectively) (p < 0.001 for all of the comparisons). The gray zone analysis revealed that the MFC-ΔSVI% values of 12 patients were in the gray zone. Of the 12, the MFC-ΔCPI% values of 7 patients were outside of the gray zone.
CONCLUSION
Fluid responsiveness can be predicted more accurately using the MFC-ΔSVI% and MFC-ΔCPI% than using the SVV and PPV. Additionally, concomitant use of the MFC-ΔSVI% and MFC-ΔCPI% is recommended, as this approach diminishes the number of patients in the gray zone.
Topics: Humans; Fluid Therapy; Male; Female; Middle Aged; Stroke Volume; Aged; Cohort Studies; Blood Pressure
PubMed: 38813019
DOI: 10.55730/1300-0144.5688 -
Frontiers in Bioscience (Landmark... May 2024The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown... (Review)
Review
The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Warburg Effect, Oncologic; Glycolysis; Antineoplastic Agents; Animals
PubMed: 38812302
DOI: 10.31083/j.fbl2905178 -
BMC Musculoskeletal Disorders May 2024This review aims to study the clinical characteristics, diagnostic results, treatments, and outcomes in patients with heterotopic ossification following COVID-19...
BACKGROUND
This review aims to study the clinical characteristics, diagnostic results, treatments, and outcomes in patients with heterotopic ossification following COVID-19 infection.
METHODS
A literature search for eligible articles was conducted using MEDLINE/Pubmed, Global Health, and Scopus databases (January 12th, 2023), including all case reports and case series from any country and language. The criteria for inclusion in this review were cases of COVID-19 infection subsequently developing heterotopic ossification.
RESULTS
This systematic review analysed 15 reports (n = 20 patients) documenting cases of heterotopic ossification following COVID-19 infection. 80% of the patients were male, with a median age of 59 years. All patients required intensive care unit stay with an average duration of 48.5 days. Mechanical ventilation was necessary for all patients and 30% of them underwent tracheostomy. Common symptoms included stiffness and pain, most frequently affecting multiple locations (70%), with the hips and shoulders being predominantly involved. X-rays were the most commonly used imaging modality, followed by computed tomography. Although treatment was given, some of the patients continued to experience symptoms, particularly stiffness.
CONCLUSION
20 patients who developed heterotopic ossification after COVID-19 have been reported, the majority of which had at least two independent risk factors for this condition. The link between those two clinical entities is therefore uncertain, requiring further investigation. It is nonetheless important to suspect heterotopic ossification in patients with severe COVID-19 infection, prolonged immobilisation, mechanical ventilation, who develop joint pain and stiffness, as this condition can significantly impact patients' quality of life.
PROTOCOL REGISTRATION
CRD42023393516.
Topics: Humans; Ossification, Heterotopic; COVID-19; Male; Middle Aged; Female; Respiration, Artificial; Aged; SARS-CoV-2; Adult
PubMed: 38811925
DOI: 10.1186/s12891-024-07537-4 -
BMC Cardiovascular Disorders May 2024Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane...
BACKGROUND
Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.
METHODS
The H9C2 cardiomyocytes were cultured to establish the hypoxia-reoxygenation (H/R) model and randomly divided into 4 groups: Control group, H/R group, sevoflurane postconditioning (H/R + SpostC) group and PI3K/AKT blocker (H/R + SpostC + LY) group. Cell survival rate was determined by CCK-8; Apoptosis rate was determined by flow cytometry; mitochondrial membrane potential was evaluated by Mito Tracker™ Red; mRNA expression levels of AKT, HIF-1α, Opa1and Drp1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR); Western Blot assay was used to detect the protein expression levels of AKT, phosphorylated AKT (p-AKT), HIF-1α, Opa1 and Drp1.
RESULTS
Compared with the H/R group, the survival rate of cardiomyocytes in the H/R + SpostC group increased, the apoptosis rate decreased and the mitochondrial membrane potential increased. qRT-PCR showed that the mRNA expression of HIF-1α and Opa1 were higher in the H/R + SpostC group compared with the H/R group, whereas the transcription level of Drp1 was lower in the H/R + SpostC group. In the H/R + SpostC + LY group, the mRNA expression of HIF-1α was lower than the H/R + SpostC group. There was no difference in the expression of Opa1 mRNA between the H/R group and the H/R + SpostC + LY group. WB assay results showed that compared with the H/R group, the protein expression levels of HIF-1α, Opa1, P-AKT were increased and Drp1 protein expression levels were decreased in the H/R + SpostC group. HIF-1α, P-AKT protein expression levels were decreased in the H/R + SpostC + LY group compared to the H/R + SpostC group.
CONCLUSION
SpostC mediates HIF-1α-regulated mitochondrial fission and fusion-related protein expression to maintain mitochondrial dynamic balance by activating the PI3K/AKT pathway and increasing AKT phosphorylation, thereby attenuating myocardial I/R injury.
Topics: Hypoxia-Inducible Factor 1, alpha Subunit; Proto-Oncogene Proteins c-akt; Animals; Myocytes, Cardiac; Sevoflurane; Signal Transduction; Myocardial Reperfusion Injury; Mitochondrial Dynamics; Cell Line; Rats; Apoptosis; Phosphatidylinositol 3-Kinase; Mitochondria, Heart; Membrane Potential, Mitochondrial; Cell Hypoxia; Dynamins; GTP Phosphohydrolases; Phosphoinositide-3 Kinase Inhibitors; Cytoprotection; Ischemic Postconditioning; Phosphorylation
PubMed: 38811893
DOI: 10.1186/s12872-024-03868-1 -
Scientific Reports May 2024Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition...
Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.
Topics: Humans; Female; Male; Middle Aged; Adult; Autonomic Nervous System; Quality of Life; Thyroiditis, Autoimmune; Heart Rate; Hypothyroidism; Thyroxine; Aged; Somatosensory Disorders; Anxiety
PubMed: 38811750
DOI: 10.1038/s41598-024-63158-w -
Scientific Reports May 2024Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard...
Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P < 0.0001), SLC2A8 (R = 0.3531, P = 0.0009) and HK1 (R = 0.3444, P = 0.0012) had the highest correlation with transplantation outcome. A multiple regression model of 11 genes increased the correlation (R = 0.6117, P < 0.0001). We conclude that assessing pre-transplant hypoxia in human islets via gene expression analysis is a rapid, viable alternative to conventional in vivo assessments. This approach also underscores the importance of mitigating pre-transplant hypoxia in isolated islets to improve the success rate of islet transplantation.
Topics: Humans; Animals; Islets of Langerhans Transplantation; Mice; Islets of Langerhans; Diabetes Mellitus, Experimental; Male; Diabetes Mellitus, Type 1; Hypoxia; Female; Cell Hypoxia; Middle Aged; Blood Glucose
PubMed: 38811610
DOI: 10.1038/s41598-024-61604-3 -
Journal of Cellular and Molecular... May 2024Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely...
Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely hypoxic cell subpopulation in glioma. Our findings reveal that the THBD macrophage subpopulation is closely associated with hypoxia in glioma, exhibiting significantly higher infiltration in tumours compared to non-tumour tissues. Moreover, a high proportion of THBD cells correlates with poor prognosis in glioblastoma (GBM) patients. Notably, THBD macrophages exhibit hypoxic characteristics and epithelial-mesenchymal transition features. Silencing THBD expression leads to a notable reduction in the proliferation and metastasis of glioma cells. Furthermore, we developed a THBD macrophage-related risk signature (THBDMRS) through machine learning techniques. THBDMRS emerges as an independent prognostic factor for GBM patients with a substantial prognostic impact. By comparing THBDMRS with 119 established prognostic features, we demonstrate the superior prognostic performance of THBDMRS. Additionally, THBDMRS is associated with glioma metastasis and extracellular matrix remodelling. In conclusion, hypoxia-related THBD macrophages play a pivotal role in glioma pathogenesis, and THBDMRS emerges as a potent and promising prognostic tool for GBM, contributing to enhanced patient survival outcomes.
Topics: Humans; Macrophages; Prognosis; Glioma; Brain Neoplasms; Epithelial-Mesenchymal Transition; Tumor Microenvironment; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Hypoxia; Biomarkers, Tumor; Risk Factors; Cell Hypoxia; Male; Female
PubMed: 38809929
DOI: 10.1111/jcmm.18393