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Theranostics 2024Current treatments for ocular angiogenesis primarily focus on blocking the activity of vascular endothelial growth factor (VEGF), but unfavorable side effects and...
Current treatments for ocular angiogenesis primarily focus on blocking the activity of vascular endothelial growth factor (VEGF), but unfavorable side effects and unsatisfactory efficacy remain issues. The identification of novel targets for anti-angiogenic treatment is still needed. We investigated the role of tsRNA-1599 in ocular angiogenesis using endothelial cells, a streptozotocin (STZ)-induced diabetic model, a laser-induced choroidal neovascularization model, and an oxygen-induced retinopathy model. CCK-8 assays, EdU assays, transwell assays, and matrigel assays were performed to assess the role of tsRNA-1599 in endothelial cells. Retinal digestion assays, Isolectin B4 (IB4) staining, and choroidal sprouting assays were conducted to evaluate the role of tsRNA-1599 in ocular angiogenesis. Transcriptomic analysis, metabolic analysis, RNA pull-down assays, and mass spectrometry were utilized to elucidate the mechanism underlying angiogenic effects mediated by tsRNA-1599. tsRNA-1599 expression was up-regulated in experimental ocular angiogenesis models and endothelial cells in response to angiogenic stress. Silencing of tsRNA-1599 suppressed angiogenic effects in endothelial cells and inhibited pathological ocular angiogenesis . Mechanistically, tsRNA-1599 exhibited little effect on VEGF signaling but could cause reduced glycolysis and NAD/NADH production in endothelial cells by regulating the expression of HK2 gene through interacting with YBX1, thus affecting endothelial effects. Targeting glycolytic reprogramming of endothelial cells by a tRNA-derived small RNA represents an exploitable therapeutic approach for ocular neovascular diseases.
PubMed: 38948065
DOI: 10.7150/thno.96946 -
Theranostics 2024: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment....
: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. : We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation , indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. In and analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.
PubMed: 38948059
DOI: 10.7150/thno.95590 -
Theranostics 2024The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between...
The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Here, an injectable H-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold to provide mechanical support. With the appropriate release of H and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Overall, our study provides critical insight into the design and development of H-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.
PubMed: 38948054
DOI: 10.7150/thno.97412 -
World Journal of Transplantation Jun 2024Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an...
BACKGROUND
Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis (PVT). The effect of PVA on portal perfusion and primary graft dysfunction (PGD) has not been assessed.
AIM
To examine the outcomes of patients who required PVA in correlation with their LT procedure.
METHODS
All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed. To account for the time-sensitive effects of graft perfusion, patients were classified into two groups: prereperfusion (pre-PVA), if the arterioportal anastomosis was performed before graft revascularization, and postreperfusion (post-PVA), if PVA was performed afterward. The pre-PVA rationale contemplated poor portal hemodynamics, severe vascular steal, or PVT. Post-PVA was considered if graft hypoperfusion became evident. Conservative interventions were attempted before PVA.
RESULTS
A total of 25 cases were identified: 15 before and 10 after graft reperfusion. Pre-PVA patients were more affected by diabetes, decompensated cirrhosis, impaired portal vein (PV) hemodynamics, and PVT. PGD was less common after pre-PVA (20.0% 60.0%) ( = 0.041). Those who developed PGD had a smaller increase in PV velocity (25.00 cm/s 73.42 cm/s) ( = 0.036) and flow (1.31 L/min 3.34 L/min) ( = 0.136) after arterialization. Nine patients required PVA closure (median time: 62 d). Pre-PVA and non-PGD cases had better survival rates than their counterparts (56.09 months 22.77 months and 54.15 months 31.91 months, respectively).
CONCLUSION
This is the largest report presenting PVA in LT. Results suggest that pre-PVA provides better graft perfusion than post-PVA. Graft hyperperfusion could play a protective role against PGD.
PubMed: 38947972
DOI: 10.5500/wjt.v14.i2.92528 -
Clinical, Cosmetic and Investigational... 2024Medication-related osteonecrosis of the jaw (MRONJ) can be a debilitating complication that can arise in patients who took or are taking antiresorptive (including...
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 bluem 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 bluem 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 bluem oral gel in this clinical case assisted in the recovery of the osteonecrosis lesion.
PubMed: 38947864
DOI: 10.2147/CCIDE.S462051 -
ACS Omega Jun 2024The long- and short-range structural chemistry of the C-type bixbyite compounds ThNdCeO, ThNdCeO, and ThNdCeO is systematically examined using synchrotron X-ray powder...
Probing the Long- and Short-Range Structural Chemistry in the C-Type Bixbyite Oxides ThNdCeO, ThNdCeO, and ThNdCeO via Synchrotron X-ray Diffraction and Absorption Spectroscopy.
The long- and short-range structural chemistry of the C-type bixbyite compounds ThNdCeO, ThNdCeO, and ThNdCeO is systematically examined using synchrotron X-ray powder diffraction (S-PXRD), high-energy resolution fluorescence detection X-ray absorption near edge (HERFD-XANES), and extended X-ray absorption fine structure spectroscopy (EXAFS) measurements supported by electronic structure calculations. S-PXRD measurements revealed that the title compounds all form classical C-type bixbyite structures in space group 3̅ that have disordered cationic crystallographic sites with further observation of characteristic superlattice reflections corresponding to oxygen vacancies. Despite the occurrence of oxygen vacancies, HERFD-XANES measurements on the Ce L-edge revealed that Ce incorporates as Ce into the structures but involves local distortion that resembles cluster behavior and loss of nearest-neighbors. In comparison, HERFD-XANES measurements on the Nd L-edge supported by electronic structure calculations reveal that Nd adopts a local coordination environment similar to the long-range C-type structure while providing charge balancing for the formation of oxygen defects. Th L-edge EXAFS analysis reveals shorter average Th-O distances in the title compounds in comparison to pristine ThO in addition to shorter Th-O and Th-Ce distances compared to Th-Th or Ce-Ce in the corresponding F-type binary oxides (ThO and CeO). These distances are further found to decrease with the increased Nd content of the structures despite simultaneous observation of the overall lattice structure progressively expanding. Linear combination calculations of the M-O bond lengths are used to help explain these observations, where the role of oxygen defects, via Nd incorporation, induces local bond contraction and enhanced Th cation valence, leading to the observed increased lattice expansion with progressive Nd incorporation. Overall, the investigation points to the significance of dissimilar cations exhibiting variable short-range chemical behavior and how it can affect the long-range structural chemistry of complex oxides.
PubMed: 38947849
DOI: 10.1021/acsomega.4c02200 -
ACS Omega Jun 2024Coalfield fires represent a critical environmental and safety concern, warranting a comprehensive understanding of the factors influencing the reactivity of oxidized...
Coalfield fires represent a critical environmental and safety concern, warranting a comprehensive understanding of the factors influencing the reactivity of oxidized coal residues within fire zones. This study investigates the influence of the oxygen volume fraction and oxidation temperature on the residual structure of oxidized coal, elucidating the underlying mechanisms driving reduced coal reactivity. The representative oxidation conditions for coalfield fire zones were determined. Through industrial and elemental analyses, complemented by methods such as infrared diffuse reflection, specific surface area determination, and pore size analysis, results indicate that higher temperatures and oxygen levels decrease volatile matter and fixed carbon, notably above 400 °C due to oxygen-deficient combustion. Hydroxyl groups decrease with a rising temperature in high oxygen conditions, while carboxyl groups increase at lower temperatures with elevated oxygen. Oxygen-lean and high-temperature conditions reinforce the coal structure, evidenced by the reduced condensation index in aromatic hydrocarbon. Oxidation alters the pore morphology, progressing from micropores to larger irregular pores through various stages, including pore formation, expansion, and merging. Elevated oxygen levels intensify oxidation, consuming the coal carbon matrix and reducing micropores, hindering internal gas diffusion, which is the key to a reduced coal reactivity in fire zones.
PubMed: 38947841
DOI: 10.1021/acsomega.4c03605 -
ACS Omega Jun 2024The advancement of water electrolyzer technologies and the production of sustainable hydrogen fuel heavily rely on the development of efficient and cost-effective...
The advancement of water electrolyzer technologies and the production of sustainable hydrogen fuel heavily rely on the development of efficient and cost-effective electrocatalysts for the oxygen evolution reaction (OER). High entropy ceramics, characterized by their unique properties, such as lattice distortion and high configurational entropy, hold significant promise for catalytic applications. In this study, we utilized the sol-gel autocombustion method to synthesize high entropy ceramics containing a combination of 3d transition metals and aluminum ((AlCrCoNiFe)O). We then compared their electrocatalytic performance with other series of synthesized multimetal and monometallic oxides for the OER under alkaline conditions. Our electrochemical analysis revealed that the high entropy ceramics exhibited excellent performance and the lowest charge transfer resistance, Tafel slope (29 mV·dec), and overpotential (η = 230 mV). These remarkable results can be primarily attributed to the high entropy effect induced by the addition of Al, Cr, Co, Ni, and Fe, which introduces increased disorder and complexity into the material's structure. This, in turn, facilitates more efficient OER catalysis by providing diverse active sites and promoting optimal electronic configurations for the reaction. Furthermore, the strong electronic interactions among the constituent elements in the metallic spinels further enhance their catalytic activity in the initiation of the OER process. Combined with the reduced charge transfer resistance, these factors collectively play pivotal roles in enhancing the OER performance of the electrocatalysts. Overall, our study provides valuable insights into the design and development of high-performance electrocatalysts for sustainable energy applications. By harnessing the high entropy effect and leveraging strong electronic interactions, electrocatalytic materials can be tailored to improve efficiency and stability, thus advancing the progress of clean energy technologies.
PubMed: 38947820
DOI: 10.1021/acsomega.4c03807 -
ACS Omega Jun 2024The durability of Pt nanoparticle catalysts is currently the most important factor limiting the widespread use of polymer electrolyte fuel cells (PEFCs). Specifically,...
The durability of Pt nanoparticle catalysts is currently the most important factor limiting the widespread use of polymer electrolyte fuel cells (PEFCs). Specifically, the Pt nanoparticles in standard carbon black-supported Pt nanoparticle (Pt/CB) catalysts repeatedly aggregate on the CB surfaces during PEFC operation, thus, reducing the performance of the cell. Therefore, PEFCs must contain large quantities of Pt to maintain sufficient service lifetimes. This is the main factor hindering the reduction of the cost of PEFCs. The present research demonstrates that ultrafine Pt particles (Pt) having diameters of approximately 0.5 nm can be formed in situ from a platinum chloride complex (PtCl ) on a carbon-based material doped with Fe and N via the dissolution and reprecipitation of Pt in the PtCl during potential cycling in a 0.1 M HClO solution. The Pt are immobilized by both Fe and N in the support material. The mass-based catalytic activity of this material during the oxygen reduction reaction is eight times higher than that of a standard Pt/CB catalyst and is maintained even after 100,000 potential step cycles (0.6 ↔ 1.0 V). The present results provide guidelines for the development of highly durable yet active membrane electrode assemblies that minimize the use of Pt.
PubMed: 38947817
DOI: 10.1021/acsomega.4c02723 -
ACS Omega Jun 2024Hypertension has earned the "silent killer" nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and...
Hypertension has earned the "silent killer" nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and protein glycation play vital roles in the pathogenesis of hypertension. Several studies have shown that they profoundly account for vascular dysfunction, endothelial damage, and disruption of blood pressure regulatory mechanisms. Of particular note are advanced glycation end products (AGEs). AGEs alter vascular tissues' functional and mechanical properties by binding to receptors for advanced glycation end products (RAGE), stimulating inflammation and free radical-mediated pathways. Propranolol, a nonselective beta-adrenergic receptor antagonist, is one of the most commonly used drugs to treat hypertension and cardiovascular diseases. Our study is the first to analyze propranolol's effects on protein glycoxidation through and approaches. Bovine serum albumin (BSA) was utilized to evaluate glycoxidation inhibition by propranolol. Propranolol (1 mM) and BSA (0.09 mM) were incubated with different glycating (0.5 M glucose, fructose, and galactose for 6 days and 2.5 mM glyoxal and methylglyoxal for 12 h) or oxidizing agents (chloramine T for 1 h). Biomarkers of protein glycation (Amadori products (APs), β-amyloid (βA), and advanced glycation end products (AGEs)), protein glycoxidation (dityrosine (DT), kynurenine (KYN), and -formylkynurenine (NFK)), protein oxidation (protein carbonyls (PCs), and advanced oxidation protein products (AOPPs)) were measured by means of colorimetric and fluorimetric methods. The scavenging of reactive oxygen species (hydrogen peroxide, hydroxyl radical, and nitric oxide) and the antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating (FIC) assays)) of propranolol were also evaluated. Additionally, docking was performed to showcase propranolol's interaction with BSA, glycosides, and AGE/RAGE pathway proteins. The products of protein glycation (↓APs, ↓βA, ↓AGEs), glycoxidation (↓DT, ↓KYN, ↓NFK), and oxidation (↓PCs, ↓AOPPs) prominently decreased in the BSA samples with both glycating/oxidizing factors and propranolol. The antiglycoxidant properties of propranolol were similar to those of aminoguanidine, a known protein oxidation inhibitor, and captopril, which is an established antioxidant. Propranolol showed a potent antioxidant activity in the FIC and HO scavenging assays, comparable to aminoguanidine and captopril. analysis indicated propranolol's antiglycative properties during its interaction with BSA, glycosidases, and AGE/RAGE pathway proteins. Our results confirm that propranolol may decrease protein oxidation and glycoxidation . Additional studies on human and animal models are vital for verification of propranolol's antiglycation activity, as this discovery might hold the key to the prevention of diabetic complications among cardiology-burdened patients.
PubMed: 38947802
DOI: 10.1021/acsomega.4c03025