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Molecular Metabolism Jan 2024Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism...
OBJECTIVE
Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity.
METHODS
We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI.
RESULTS
MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival.
CONCLUSIONS
Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.
Topics: Mice; Animals; Monocarboxylic Acid Transporters; Acute Kidney Injury; Oxidation-Reduction; Rhabdomyolysis; Oxidants
PubMed: 38056691
DOI: 10.1016/j.molmet.2023.101849 -
PloS One 2023The current study describes the biogenic synthesis of two metal oxides zinc oxide (ZnO), aluminum oxide (Al2O3) nanoparticles using Camellia sinensis, and Origanum...
Biogenic synthesis of ZnO and Al2O3 nanoparticles using Camellia sinensis and Origanum vulgare L. leaves extract for spectroscopic estimation of ofloxacin and ciprofloxacin in commercial formulations.
The current study describes the biogenic synthesis of two metal oxides zinc oxide (ZnO), aluminum oxide (Al2O3) nanoparticles using Camellia sinensis, and Origanum vulgare L. leaves extract, respectively. The synthesized metal oxide nanoparticles were investigated using spectroscopic and microscopic techniques to confirm the formation of their nanostructures. Accurate and precise spectrofluorometric probes were proposed for the quantification of Ofloxacin (OFX) and Ciprofloxacin (CPFX) in their bulk and commercial formulations. The extraordinary properties of Zinc oxide and aluminum oxide nanoparticles (ZnONPs and Al2O3NPs) enhance the fluorescence intensity in the presence of 0.5 mL and 1.0 mL of sodium dodecyl sulfate (SDS, 1.0% w/v) as organizing agent for the detection of OFX and CPFX, respectively. The optical detection of both drugs at λex/em range 250-700 nm displayed linearity with a main correlation coefficient >0.999 at 1-300 (OFX-SDS-ZnONPs) and 0.5-100 (OFX-SDS-Al2O3NPs) ng mL-1,10-400 (CPFX-SDS-ZnONPs) and 0.1-50 (CPFX-SDS-Al2O3NPs) ng mL-1. The detection and quantification limits were found to be 0.04, 0.03, and 0.02, 0.04 ng mL-1, 0.13, 0.10, and 7.24, 0.09 ng mL-1 for the above-mentioned fluorescence systems, respectively. The suggested spectrofluorometric probes were validated and potentially applied for the estimation of OFX and CPFX in their bulk and commercial formulations.
Topics: Ofloxacin; Zinc Oxide; Ciprofloxacin; Camellia sinensis; Origanum; Nanoparticles; Metal Nanoparticles; Oxides; Aluminum Oxide
PubMed: 37906583
DOI: 10.1371/journal.pone.0286341 -
Journal of Atherosclerosis and... Nov 2023Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary...
AIMS
Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH.
METHODS
In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1.
RESULTS
In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A.
CONCLUSIONS
Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.
Topics: Humans; Hypertension, Pulmonary; Endothelin-1; Chronic Disease; Thrombosis; Endarterectomy; Oxidants; RNA, Messenger; Pulmonary Embolism
PubMed: 37005330
DOI: 10.5551/jat.63973 -
International Journal of Molecular... Jun 2023Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signalling pathways to foster drug resistance, cancer stem cell survival,...
Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signalling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial-mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukaemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukaemia cells, and that these responses were enhanced when TG2 was deleted. The combined ATRA + ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of the cellular oxidative stress response, and calpain proteolytic activity, resulting in TG2 degradation and the reduced survival of WT leukaemia cells. We further showed that the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line and primary peripheral blood mononuclear cells upon ATO treatment, thereby sensitising these cell types to apoptotic signals.
Topics: Humans; Arsenic Trioxide; Calpain; Reactive Oxygen Species; Protein Glutamine gamma Glutamyltransferase 2; Leukocytes, Mononuclear; Leukemia, Promyelocytic, Acute; Tretinoin; Apoptosis; Oxides; Arsenicals
PubMed: 37446117
DOI: 10.3390/ijms241310938 -
Redox Biology Jul 2023Exacerbated hypochlorite (OCl) production is linked to neurodegenerative processes, but there is growing evidence that lower levels of hypochlorite activity are...
Exacerbated hypochlorite (OCl) production is linked to neurodegenerative processes, but there is growing evidence that lower levels of hypochlorite activity are important to protein homeostasis. In this study we characterise the effects of hypochlorite on the aggregation and toxicity of amyloid beta peptide 1-42 (Aβ), a major component of amyloid plaques that form in the brain in Alzheimer's disease. Our results demonstrate that treatment with hypochlorite promotes the formation of Aβ assemblies ≥100 kDa that have reduced surface exposed hydrophobicity compared to the untreated peptide. This effect is the result of the oxidation of Aβ at a single site as determined by mass spectrometry analysis. Although treatment with hypochlorite promotes the aggregation of Aβ, the solubility of the peptide is enhanced and amyloid fibril formation is inhibited as assessed by filter trap assay, thioflavin T assay and transmission electron microscopy. The results of in vitro assays using SH-SY5Y neuroblastoma cells show that pre-treatment of Aβ with a sub-stoichiometric amount of hypochlorite substantially reduces its toxicity. The results of flow cytometry analysis and internalisation assays indicate that hypochlorite-induced modification of Aβ reduces its toxicity via at least two-distinct mechanism, reducing the total binding of Aβ to the surface of cells and facilitating the cell surface clearance of Aβ to lysosomes. Our data is consistent with a model in which tightly regulated production of hypochlorite in the brain is protective against Aβ-induced toxicity.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Hypochlorous Acid; Peptide Fragments
PubMed: 37216700
DOI: 10.1016/j.redox.2023.102736 -
Journal of Nanobiotechnology May 2024Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide...
Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO) that was core coated with a MnO shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO@MnO@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.
Topics: Animals; Mice; Immunotherapy; Oxides; Female; Nucleotidyltransferases; Manganese Compounds; Cell Line, Tumor; Mice, Inbred BALB C; Nanoparticles; Radiation-Sensitizing Agents; Membrane Proteins; Ferroptosis; Glucose Oxidase; Reactive Oxygen Species; Humans; DNA Damage; Tumor Microenvironment
PubMed: 38724978
DOI: 10.1186/s12951-024-02502-8 -
Biosensors May 2024Nanostructured metal oxides (NMOs) provide electrical properties such as high surface-to-volume ratio, reaction activity, and good adsorption strength. Furthermore, they... (Review)
Review
Nanostructured metal oxides (NMOs) provide electrical properties such as high surface-to-volume ratio, reaction activity, and good adsorption strength. Furthermore, they serve as a conductive substrate for the immobilization of biomolecules, exhibiting notable biological activity. Capitalizing on these characteristics, they find utility in the development of various electrochemical biosensing devices, elevating the sensitivity and selectivity of such diagnostic platforms. In this review, different types of NMOs, including zinc oxide (ZnO), titanium dioxide (TiO), iron (II, III) oxide (FeO), nickel oxide (NiO), and copper oxide (CuO); their synthesis methods; and how they can be integrated into biosensors used for medical diagnosis are examined. It also includes a detailed table for the last 10 years covering the morphologies, analysis techniques, analytes, and analytical performances of electrochemical biosensors developed for medical diagnosis.
Topics: Biosensing Techniques; Electrochemical Techniques; Nanostructures; Humans; Oxides; Nickel; Titanium; Zinc Oxide; Metals; Copper
PubMed: 38785712
DOI: 10.3390/bios14050238 -
Surface and intra-pulpal temperature variation during tooth whitening photoactivated with LED/laser.Dental Materials Journal Sep 2023This study evaluated the variation of surface and intra-pulpal temperature, during bleaching protocol, using LED/laser. The 35% (HP35), 15% (HP15) and 6% (HP6) gels were...
This study evaluated the variation of surface and intra-pulpal temperature, during bleaching protocol, using LED/laser. The 35% (HP35), 15% (HP15) and 6% (HP6) gels were used associated with LED/laser applied every 1 min for 30 min in a human canine. The evaluation of surface temperature variation (∆Ts) was performed using a pHmeter and the intra-pulpal temperature variation (∆Ti) was performed using a digital thermometer, at times of 1-, 5-, 10- 15- and 30-min. Statistical analysis was performed using the two-way repeated measures ANOVA test and Bonferroni post-hoc test was used at a significance level of 5%. HP35 and HP15 showed greater temperature variation than HP6 up to 10 min of surface evaluation, showing no differences between them. In the intra-pulpal evaluation, no group showed differences throughout the procedure.
Topics: Humans; Tooth Bleaching; Temperature; Hydrogen Peroxide; Light; Tooth Bleaching Agents; Lasers
PubMed: 37460305
DOI: 10.4012/dmj.2023-017 -
Journal of Nanobiotechnology Oct 2023Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However,...
BACKGROUND
Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility.
RESULTS
In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. HO treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFκB activator tumor necrosis factor α and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFκB and MAPK signaling pathways.
CONCLUSIONS
The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment.
Topics: Humans; Rats; Animals; Antioxidants; Reactive Oxygen Species; Hydrogen Peroxide; Oxidative Stress; Mesenchymal Stem Cells; Regeneration; Nanoparticles; Tendons; Tendon Injuries; Umbilical Cord
PubMed: 37789395
DOI: 10.1186/s12951-023-02125-5 -
Applied and Environmental Microbiology Aug 2023An important role of nitric oxide (NO) as either a free intermediate in the NH oxidation pathway or a potential oxidant for NH or NHOH has been proposed for...
An important role of nitric oxide (NO) as either a free intermediate in the NH oxidation pathway or a potential oxidant for NH or NHOH has been proposed for ammonia-oxidizing bacteria (AOB) and archaea (AOA), respectively. However, tracing NO metabolism at low concentrations remains notoriously difficult. Here, we use electrochemical sensors and the mild NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) to trace apparent NO concentration and determine production rates at low micromolar concentrations in the model AOB strain Nitrosomonas europaea. In agreement with previous studies, we found that PTIO does not affect NH oxidation instantaneously in both Nitrosospira briensis and Nitrosomonas europaea, unlike inhibitors for ammonia oxidation such as allylthiourea and acetylene, although it effectively scavenged NO from the cell suspensions. Quantitative analysis showed that NO production by amounted to 3.15% to 6.23% of NO production, whereas grown under O limitation produced NO equivalent to up to 40% of NO production at high substrate concentrations. In addition, we found that PTIO addition to grown under O limitation abolished NO production. These results indicate different turnover rates of NO during NH oxidation under O-replete and O-limited growth conditions in AOB. The results suggest that NO may not be a free intermediate or remain tightly bound to iron centers of enzymes during hydroxylamine oxidation and that only NH saturation and adaptation to O limitation may lead to significant dissociation of NO from hydroxylamine dehydrogenase. Ammonia oxidation by chemolithoautotrophic ammonia-oxidizing bacteria (AOB) is thought to contribute significantly to global nitrous oxide (NO) emissions and leaching of oxidized nitrogen, particularly through their activity in nitrogen (N)-fertilized agricultural production systems. Although substantial efforts have been made to characterize the N metabolism in AOB, recent findings suggest that nitric oxide (NO) may play an important mechanistic role as a free intermediate of hydroxylamine oxidation in AOB, further implying that besides hydroxylamine dehydrogenase (HAO), additional enzymes may be required to complete the ammonia oxidation pathway. However, the NO spin trap PTIO was found to not inhibit ammonia oxidation in AOB. This study provides a combination of physiological and spectroscopic evidence that PTIO indeed scavenges only free NO in AOB and that significant amounts of free NO are produced only during incomplete hydroxylamine oxidation or nitrifier denitrification under O-limited growth conditions.
Topics: Nitric Oxide; Ammonia; Hydroxylamine; Nitrogen Dioxide; Oxidation-Reduction; Nitrous Oxide; Archaea; Betaproteobacteria; Nitrogen; Hydroxylamines; Nitrification
PubMed: 37439697
DOI: 10.1128/aem.02173-22