UNASSIGNED: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization.
UNASSIGNED: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed.
UNASSIGNED: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss.
UNASSIGNED: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

暂无摘要。

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

OBJECTIVE: Studies exploring variations in peripheral muscle oxygenation and pressure pain thresholds (PPT) of masticatory muscles in individuals with Temporomandibular Disorders (TMDs) are limited. The purpose of this study was to compare variations in peripheral oxygenation of the masseter muscle; PPT of the masseter and temporal muscles and correlate peripheral muscle oxygenation and PPT of the masseter muscle in individuals with different types of TMDs.
METHODS: Cross-sectional study involving 116 participants classified into three groups: muscle group (MG, n = 32), joint group (JG, n = 30) and muscle-joint group (MJG, n = 54). Individuals aged 26.97 ± 6.93, 68.97% female, 31,03% males were included. All participants were evaluated using the Diagnostic Criteria for Temporomandibular Disorders, Near-infrared spectroscopy (NIRS) for peripheral muscle oxygenation and pressure algometer for PPT.
RESULTS: There was no difference in masseter muscle oxygenation among groups. In the masseter muscle, a weakly positive correlation was observed between PPT and variation in tissue saturation index in the MG (rho = 0.365) and JG (rho = 0.317). In addition, the MJG expressed lower PPT (p = 0.004) than JG, demonstrating that MJG had more pain in this muscle.
CONCLUSIONS: MJG have lower PPT in the masseter muscle. Although the PPT is dependent on the type of TMDs, the correlation between PPT and oxygenation is weak. All TMDs groups evaluated (MG, JG, MJG) showed hemodynamic similarities of the masseter muscle.
CONCLUSIONS: Understanding pain thresholds and the hemodynamic behavior of the masticatory muscles contributes to a more assertive physiotherapeutic assessment in TMDs, serving as a basis for careful and individualized interventions.

The impact of ocean warming on fish and fisheries is vigorously debated. Leading theories project limited adaptive capacity of tropical fishes and 14-39% size reductions by 2050 due to mass-scaling limitations of oxygen supply in larger individuals. Using the world\'s hottest coral reefs in the Persian/Arabian Gulf as a natural laboratory for ocean warming - where species have survived >35.0 °C summer temperatures for over 6000 years and are 14-40% smaller at maximum size compared to cooler locations - we identified two adaptive pathways that enhance survival at elevated temperatures across 10 metabolic and swimming performance metrics. Comparing Lutjanus ehrenbergii and Scolopsis ghanam from reefs both inside and outside the Persian/Arabian Gulf across temperatures of 27.0 °C, 31.5 °C and 35.5 °C, we reveal that these species show a lower-than-expected rise in basal metabolic demands and a right-shifted thermal window, which aids in maintaining oxygen supply and aerobic performance to 35.5 °C. Importantly, our findings challenge traditional oxygen-limitation theories, suggesting a mismatch in energy acquisition and demand as the primary driver of size reductions. Our data support a modified resource-acquisition theory to explain how ocean warming leads to species-specific size reductions and why smaller individuals are evolutionarily favored under elevated temperatures.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5\'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.

Medication-related osteonecrosis of the jaw (MRONJ) can be a debilitating complication that can arise in patients who took or are taking antiresorptive (including bisphosphonates) or antiangiogenic agents, leading to visible bone or a fistula that continues for more than eight weeks, without any history of radiotherapy. This clinical case aimed to describe the treatment of MRONJ with topical active oxygen therapy using blue®m oral gel. A 63-year-old female patient that had been taking weekly sodium alendronate (70 mg) for four years by oral via, presented discomfort and implant movement in the #46 region, by that underwent surgical extraction of the implant. After three months the patient returned and was diagnosed with MRONJ. Initially, conventional therapies were performed, including surgical debridement and antibiotic therapy, but without success. The patient still had clinical signs of osteonecrosis six months after the implant extraction. The entire socket was then filled with blue®m oral gel by topical application. The patient was instructed to continue applying the gel to the region every 8 hours for 15 days. After this period, the patient returned, and it was observed that the wound was in the healing process, with the presence of epithelialized tissue and without bone exposure. The 2-year clinical follow-up showed the lesion had healed entirely, and a new implant was installed. After the osseointegration period, the final prosthesis was placed. The patient remains under clinical follow-up. Therefore, it can be concluded that the application of blue®m oral gel in this clinical case assisted in the recovery of the osteonecrosis lesion.

OBJECTIVE: This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
METHODS: A mathematical model was developed to simulate the changes in cerebral tissue pO2, glucose concentration, and temperature due to blood flow interruptions. The model considers variations in baseline cerebral blood flow (CBF), capillary density, and blood oxygen/glucose levels, as well as ambient temperature changes.
RESULTS: Simulations indicate that complete blood flow obstruction still allows for limited glucose availability, supporting nonoxidative metabolism and potentially exacerbating lactate buildup and acidosis. Partial obstructions decrease tissue pO2, with minimal impact on glucose level, which can remain almost unchanged or even slightly increase. Reduced CBF, capillary density, or blood oxygen due to aging or disease enhances hypoxia risk at lower obstruction levels, with capillary density having a significant effect on stroke severity by influencing both pO2 and glucose levels. Conditions could lead to co-occurrence of hypoxia/hypoglycemia or hypoxia/hyperglycemia, each worsening outcomes. Temperature effects were minimal in deep brain regions but varied near the skull by 0.2-0.8°C depending on ambient temperature.
CONCLUSIONS: The model provides insights into the conditions driving severe stroke outcomes based on estimated levels of hypoxia, hypoglycemia, hyperglycemia, and temperature changes.

OBJECTIVE: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.
METHODS: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm3) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.
RESULTS: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.
CONCLUSIONS: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.