Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 18.608
Filter
1.
Anal Chim Acta ; 1312: 342749, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834263

ABSTRACT

Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover, pharmacologically, CO has been substantiated for its therapeutic advantages in animal models of diverse pathological conditions. Given that an excessive level of CO can be toxic, it is imperative to quantify the necessary amount for therapeutic use accurately. However, estimating gaseous CO is notably challenging. Therefore, novel techniques are essential to quantify CO in therapeutic applications and overcome this obstacle precisely. The classical Myoglobin (Mb) assay technique has been extensively used to determine the amount of CO-release from CO-releasing molecules (CORMs) within therapeutic contexts. Nevertheless, specific challenges arise when applying the Mb assay to evaluate CORMs featuring innovative molecular architectures. Here, we report a fluorinated photo-CORM (CORM-FBS) for the photo-induced CO-release. We employed the 19F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new 19F NMR approach opens immense opportunities for researchers to develop reliable techniques for identifying molecular structures, quantitative studies of drug metabolism, and monitoring the reaction process.


Subject(s)
Carbon Monoxide , Light , Myoglobin , Carbon Monoxide/analysis , Myoglobin/chemistry , Magnetic Resonance Spectroscopy/methods , Fluorine/chemistry , Animals , Photochemical Processes
2.
Environ Monit Assess ; 196(6): 545, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38740605

ABSTRACT

In Tunisia, urban air pollution is becoming a bigger problem. This study used a combined strategy of biomonitoring with lichens and satellite mapping with Sentinel-5 satellite data processed in Google Earth Engine (GEE) to assess the air quality over metropolitan Tunis. Lichen diversity was surveyed across the green spaces of the Faculty of Science of Tunisia sites, revealing 15 species with a predominance of pollution-tolerant genera. The Index of Atmospheric Purity (IAP) calculated from the lichen data indicated poor air quality. Spatial patterns of pollutants sulfur dioxide (SO2), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO), and aerosol index across Greater Tunis were analyzed from Sentinel-5 datasets on the GEE platform. The higher values of these indices in the research area indicate that it may be impacted by industrial activity and highlight the considerable role that vehicle traffic plays in air pollution. The results of the IAP, IBL, and the combined ground-based biomonitoring and satellite mapping techniques confirm poor air quality and an environment affected by atmospheric pollutants which will enable proactive air quality management strategies to be put in place in Tunisia's rapidly expanding cities.


Subject(s)
Air Pollutants , Air Pollution , Environmental Monitoring , Lichens , Ozone , Sulfur Dioxide , Lichens/chemistry , Environmental Monitoring/methods , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Tunisia , Ozone/analysis , Sulfur Dioxide/analysis , Nitrogen Dioxide/analysis , Cities , Satellite Imagery , Carbon Monoxide/analysis
3.
Chemosphere ; 358: 142198, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697566

ABSTRACT

In the electrical industry, there are many hazardous gases that pollute the environment and even jeopardize human health, so timely detection and effective control of these hazardous gases is of great significance. In this work, the gas-sensitive properties of Pd-modified g-C3N4 interface for each hazardous gas molecule were investigated from a microscopic viewpoint, taking the hazardous gases (CO, NOx) that may be generated in the power industry as the detection target. Then, the performance of Pd-modifiedg-C3N4 was evaluated for practical applications as a gas sensor material. Novelly, an unconventional means was designed to briefly predict the effect of humidity on the adsorption properties of this sensor material. The final results found that Pd-modified g-C3N4 is most suitable as a potential gas-sensitizing material for NO2 gas sensors, followed by CO. Interestingly, Pd-modified g-C3N4 is less suitable as a potential gas-sensitizing material for NO gas sensors, but has the potential to be used as a NO cleaner (adsorbent). Unconventional simulation explorations of humidity effects show that in practical applications Pd-modified g-C3N4 remains a promising material for gas sensing in specific humidity environments. This work reveals the origin of the excellent properties of Pd-modified g-C3N4 as a gas sensor material and provides new ideas for the detection and treatment of these three hazardous gases.


Subject(s)
Air Pollutants , Palladium , Air Pollutants/analysis , Palladium/chemistry , Adsorption , Water/chemistry , Environmental Monitoring/methods , Gases/analysis , Humidity , Carbon Monoxide/analysis , Nitriles/chemistry , Nitriles/analysis
4.
J Environ Manage ; 359: 121017, 2024 May.
Article in English | MEDLINE | ID: mdl-38718602

ABSTRACT

Energy transition currently brings focus on fuel cell micro-combined heat and power (mCHP) systems for residential uses. The two main technologies already commercialized are the Proton Exchange Membrane Fuel Cells (PEMFCs) and Solid Oxide Fuel Cells (SOFCs). The pollutant emissions of one system of each technology have been tested with a portable probe both in laboratory and field-test configurations. In this paper, the nitrogen oxides (NOx), sulphur dioxide (SO2), and carbon monoxide (CO) emission levels are compared to other combustion technologies such as a recent Euro 6 diesel automotive vehicle, a classical gas condensing boiler, and a gas absorption heat pump. At last, a method of converting the concentration of pollutants (in ppm) measured by the sensors into pollutant intensity per unit of energy (in mg/kWh) is documented and reported. This allows for comparing the pollutant emissions levels with relevant literature, especially other studies conducted with other measuring sensors. Both tested residential fuel cell technologies fed by natural gas can be considered clean regarding SO2 and NOx emissions. The CO emissions can be considered quite low for the tested SOFC and even nil for the tested PEMFC. The biggest issue of natural gas fuel cell technologies still lies in the carbon dioxide (CO2) emissions associated with the fossil fuel they consume. The gas absorption heat pump however shows worse NOx and CO levels than the classical gas condensing boiler. At last, this study illustrates that the high level of hybridization between a fuel cell and a gas boiler may be responsible for unexpected ON/OFF cycling behaviours and therefore prevent both sub-systems from operating as optimally and reliably as they would have as standalone units.


Subject(s)
Air Pollutants , Nitrogen Oxides , Air Pollutants/analysis , Nitrogen Oxides/analysis , Carbon Monoxide/analysis , Sulfur Dioxide/analysis , Benchmarking , Vehicle Emissions/analysis , Environmental Monitoring/methods
5.
Environ Monit Assess ; 196(6): 521, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714584

ABSTRACT

The transport sector is considered the largest contributor of air pollutants in urban areas, mainly on-road vehicles, affecting the environment and human health. Bahía Blanca is a medium-sized Latin American city, with high levels of traffic in the downtown area during peak hours. In this regard, it is necessary to analyze air pollution using an air quality model considering that there are no air pollutant measurements in the central area. Furthermore, this type of study has not been carried out in the region and since the city is expected to grow, it is necessary to evaluate the current situation in order to make effective future decisions. In this sense, the AERMOD model (US-EPA version) and the RLINE source type were used in this work. This study analyzes the variations of pollutant concentrations coming from mobile sources in Bahía Blanca's downtown area, particularly carbon monoxide (CO) and nitrogen oxides (NOx) during the period Jul-2020 to Jun-2022. It is interesting to note the results show the maximum concentration values detected are not directly associated with maximum levels of vehicle flow or emission rates, which highlights the importance of meteorological parameters in the modeling. In addition, alternative scenarios are proposed and analyzed from a sustainable approach. Regarding the scenario analysis, it can be concluded that diesel vehicles have a large influence on NOx emissions. Moreover, restrictions as strict as those proposed for a Low Emission Zone would be less applicable in the city than alternative temporary measures that modify traffic at peak hours.


Subject(s)
Air Pollutants , Air Pollution , Carbon Monoxide , Cities , Environmental Monitoring , Vehicle Emissions , Environmental Monitoring/methods , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Vehicle Emissions/analysis , Carbon Monoxide/analysis , Nitrogen Oxides/analysis , Latin America , Models, Theoretical , Particulate Matter/analysis
6.
Microb Cell Fact ; 23(1): 125, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698392

ABSTRACT

BACKGROUND: The facultatively anaerobic thermophile Parageobacillus thermoglucosidasius is able to produce hydrogen gas (H2) through the water-gas shift (WGS) reaction. To date this process has been evaluated under controlled conditions, with gas feedstocks comprising carbon monoxide and variable proportions of air, nitrogen and hydrogen. Ultimately, an economically viable hydrogenogenic system would make use of industrial waste/synthesis gases that contain high levels of carbon monoxide, but which may also contain contaminants such as H2, oxygen (O2) and other impurities, which may be toxic to P. thermoglucosidasius. RESULTS: We evaluated the effects of synthesis gas (syngas) mimetic feedstocks on WGS reaction-driven H2 gas production by P. thermoglucosidasius DSM 6285 in small-scale fermentations. Improved H2 gas production yields and faster onset towards hydrogen production were observed when anaerobic synthetic syngas feedstocks were used, at the expense of biomass accumulation. Furthermore, as the WGS reaction is an anoxygenic process, we evaluated the influence of O2 perturbation on P. thermoglucosidasius hydrogenogenesis. O2 supplementation improved biomass accumulation, but reduced hydrogen yields in accordance with the level of oxygen supplied. However, H2 gas production was observed at low O2 levels. Supplementation also induced rapid acetate consumption, likely to sustain growth. CONCLUSION: The utilisation of anaerobic syngas mimetic gas feedstocks to produce H2 and the relative flexibility of the P. thermoglucosidasius WGS reaction system following O2 perturbation further supports its applicability towards more robust and continuous hydrogenogenic operation.


Subject(s)
Fermentation , Hydrogen , Oxygen , Hydrogen/metabolism , Oxygen/metabolism , Carbon Monoxide/metabolism , Anaerobiosis , Biomass , Gases/metabolism
7.
Dalton Trans ; 53(23): 9612-9656, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38808485

ABSTRACT

Carbon monoxide, the "silent killer" gas, is increasingly recognised as an important signalling molecule in human physiology, which has beneficial biological properties. A particular way of achieving controlled CO administration is based on the use of biocompatible molecules that only release CO when triggered by internal or external factors. These approaches include the development of pharmacologically effective prodrugs known as CO releasing molecules (CORMs), which can supply biological systems with CO in well-regulated doses. An overview of transition metal-based CORMs with cytotoxic properties is here reported. The mechanisms at the basis of the biological activities of these molecules and their potential therapeutical applications with respect to their stability and CO releasing properties have been discussed. The activation of metal-based CORMs is determined by the type of metal and by the nature and features of the auxiliary ligands, which affect the metal core electronic density and therefore the prodrug resistance towards oxidation and CO release ability. A major role in regulating the cytotoxic properties of these CORMs is played by CO and/or CO-depleted species. However, several mysteries concerning the cytotoxicity of CORMs remain as intriguing questions for scientists.


Subject(s)
Carbon Monoxide , Prodrugs , Carbon Monoxide/chemistry , Carbon Monoxide/pharmacology , Humans , Prodrugs/chemistry , Prodrugs/pharmacology , Animals , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Transition Elements/chemistry
8.
J Nanobiotechnology ; 22(1): 277, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783332

ABSTRACT

Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI.


Subject(s)
Gasotransmitters , Spinal Cord Injuries , Spinal Cord Injuries/therapy , Humans , Animals , Gasotransmitters/therapeutic use , Gasotransmitters/metabolism , Nitric Oxide/metabolism , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Hydrogen Sulfide/therapeutic use , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Carbon Monoxide/metabolism , Carbon Monoxide/therapeutic use , Oxygen/metabolism , Spinal Cord , Hydrogen/therapeutic use , Hydrogen/pharmacology
9.
BMC Public Health ; 24(1): 1411, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802825

ABSTRACT

BACKGROUND: Preterm birth (PTB) is an important predictor of perinatal morbidity and mortality. Previous researches have reported a correlation between air pollution and an increased risk of preterm birth. However, the specific relationship between short-term and long-term exposure to carbon monoxide (CO) and preterm birth remains less explored. METHODS: A population-based study was conducted among 515,498 pregnant women in Chongqing, China, to assess short-term and long-term effects of CO on preterm and very preterm births. Generalized additive models (GAM) were applied to evaluate short-term effects, and exposure-response correlation curves were plotted after adjusting for confounding factors. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using COX proportional hazard models to estimate the long-term effect. RESULTS: The daily incidence of preterm and very preterm birth was 5.99% and 0.41%, respectively. A positive association between a 100 µg/m³ increase in CO and PTB was observed at lag 0-3 days and 12-21 days, with a maximum relative risk (RR) of 1.021(95%CI: 1.001-1.043). The exposure-response curves (lag 0 day) revealed a rapid increase in PTB due to CO. Regarding long-term exposure, positive associations were found between a 100 µg/m3 CO increase for each trimester(Model 2 for trimester 1: HR = 1.054, 95%CI: 1.048-1.060; Model 2 for trimester 2: HR = 1.066, 95%CI: 1.060-1.073; Model 2 for trimester 3: HR = 1.007, 95%CI: 1.001-1.013; Model 2 for entire pregnancy: HR = 1.080, 95%CI: 1.073-1.088) and higher HRs of very preterm birth. Multiplicative interactions between air pollution and CO on the risk of preterm and very preterm birth were detected (P- interaction<0.05). CONCLUSIONS: Our findings suggest that short-term exposure to low levels of CO may have protective effects against preterm birth, while long-term exposure to low concentrations of CO may reduce the risk of both preterm and very preterm birth. Moreover, our study indicated that very preterm birth is more susceptible to the influence of long-term exposure to CO during pregnancy, with acute CO exposure exhibiting a greater impact on preterm birth. It is imperative for pregnant women to minimize exposure to ambient air pollutants.


Subject(s)
Air Pollutants , Carbon Monoxide , Premature Birth , Humans , Female , Pregnancy , Premature Birth/epidemiology , China/epidemiology , Carbon Monoxide/analysis , Adult , Air Pollutants/analysis , Air Pollutants/adverse effects , Air Pollution/adverse effects , Air Pollution/analysis , Infant, Newborn , Maternal Exposure/adverse effects , Maternal Exposure/statistics & numerical data , Time Factors , Young Adult , Risk Factors
10.
Nat Commun ; 15(1): 4151, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755154

ABSTRACT

Atmospheric methane oxidizing bacteria (atmMOB) constitute the sole biological sink for atmospheric methane. Still, the physiological basis allowing atmMOB to grow on air is not well understood. Here we assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source. Four species, including three outside the canonical atmMOB group USCα, enduringly oxidized atmospheric methane, carbon monoxide, and hydrogen during 12 months of growth on air. These four species exhibited distinct substrate preferences implying the existence of multiple metabolic strategies to grow on air. The estimated energy yields of the atmMOB were substantially lower than previously assumed necessary for cellular maintenance in atmMOB and other aerobic microorganisms. Moreover, the atmMOB also covered their nitrogen requirements from air. During growth on air, the atmMOB decreased investments in biosynthesis while increasing investments in trace gas oxidation. Furthermore, we confirm that a high apparent specific affinity for methane is a key characteristic of atmMOB. Our work shows that atmMOB grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air and outlines the metabolic strategies that enable atmMOB to mitigate greenhouse gases.


Subject(s)
Carbon Monoxide , Hydrogen , Methane , Oxidation-Reduction , Methane/metabolism , Carbon Monoxide/metabolism , Hydrogen/metabolism , Atmosphere/chemistry , Air , Nitrogen/metabolism , Greenhouse Gases/metabolism
11.
PLoS One ; 19(5): e0302653, 2024.
Article in English | MEDLINE | ID: mdl-38748750

ABSTRACT

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.


Subject(s)
Carbon Monoxide , Disease Models, Animal , Animals , Swine , Carbon Monoxide/pharmacology , Carbon Monoxide/metabolism , Heart Arrest/therapy , Out-of-Hospital Cardiac Arrest/therapy , Male , Cardiopulmonary Resuscitation/methods
12.
J Hazard Mater ; 472: 134505, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38703689

ABSTRACT

It is critical to explore intervenable environmental factors in suicide mortality. Based on 30,688 suicide cases obtained from the Mortality Surveillance System of the Jiangsu Provincial Centre for Disease Control and Prevention, we utilized a case-crossover design, and found that the OR of suicide deaths increased by a maximum of 0.71 % (95 % CI: 0.09 %, 1.32 %), 0.68 % (95 % CI: 0.12 %, 1.25 %), 0.77 % (95 % CI: 0.19 %, 1.37 %), 2.95 % (95 % CI: 1.62 %, 4.29 %), 4.18 % (95 % CI: 1.55 %, 6.88 %), and 0.93 % (95 % CI: 0.10 %, 1.77 %), respectively, for per 10 µg/m3 increase in the particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and per 0.1 mg/m3 increase in carbon monoxide (CO) concentrations with the conditional logistic regression analysis. People living in county-level cities were more susceptible. Particularly, a significant positive association was found between air pollutant mixture exposure and suicide deaths (OR=1.04,95 % CI: 1.01, 1.06). The excess fraction of suicide deaths due to air pollution reached a maximum of 8.07 %. In conclusion, we found associations between individual and mixed ambient air pollutants and suicide deaths, informing the development of integrated air pollution management and targeted measures for suicide prevention and intervention. ENVIRONMENTAL IMPLICATION: As a major contributor to the global burden of disease, air pollution was confirmed by accumulating studies to have adverse impact on mental health, and potentially lead to suicide deaths. However, systematic studies on the association between air pollution and suicide mortality are lacking. We explored the associations of multiple air pollutants and pollution mixtures with suicide deaths and assessed excess suicide mortality due to air pollution, emphasizing the importance of air pollution control on suicide prevention. Our study provides evidence to support mechanistic studies on the association between air pollution and suicide, and informs comprehensive air pollution management.


Subject(s)
Air Pollutants , Cross-Over Studies , Particulate Matter , Suicide , Humans , Suicide/statistics & numerical data , Air Pollutants/toxicity , Air Pollutants/analysis , Particulate Matter/toxicity , Particulate Matter/analysis , Male , Female , Middle Aged , Adult , China/epidemiology , Ozone/toxicity , Ozone/analysis , Sulfur Dioxide/analysis , Nitrogen Dioxide/analysis , Nitrogen Dioxide/toxicity , Aged , Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/adverse effects , Carbon Monoxide/analysis , Carbon Monoxide/toxicity , Young Adult
13.
ACS Biomater Sci Eng ; 10(6): 4009-4017, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38722972

ABSTRACT

It still remains challenging to design multifunctional therapeutic reagents for effective cancer therapy under a unique tumor microenvironment including insufficient endogenous H2O2 and O2, low pH, and a high concentration of glutathione (GSH). In this work, a CO-based phototherapeutic system triggered by photogenerated holes, which consisted of ionic liquid (IL), the CO prodrug Mn2(CO)10, and iridium(III) porphyrin (IrPor) modified carbonized ZIF-8-doped graphitic carbon nitride nanocomposite (IL/ZCN@Ir(CO)), was designed for cascade hypoxic tumors. Upon light irradiation, the photogenerated holes on IL/ZCN@Ir(CO) oxidize water into H2O2, which subsequently induces Mn2(CO)10 to release CO. Meanwhile, IrPor can convert H2O2 to hydroxyl radical (•OH) and subsequent singlet oxygen (1O2), which further triggers CO release. Moreover, the degraded MnO2 shows activity for glutathione (GSH) depletion and mimics peroxidase, leading to GSH reduction and •OH production in tumors. Thus, this strategy can in situ release high concentrations of CO and reactive oxygen species (ROS) and deplete GSH to efficiently induce cell apoptosis under hypoxic conditions, which has a high inhibiting effect on the growth of tumors, offering an attractive strategy to amplify CO and ROS generation to meet therapeutic requirements in cancer treatment.


Subject(s)
Carbon Monoxide , Glutathione , Carbon Monoxide/metabolism , Carbon Monoxide/chemistry , Carbon Monoxide/pharmacology , Humans , Glutathione/metabolism , Glutathione/chemistry , Animals , Cell Line, Tumor , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/radiotherapy , Tumor Hypoxia/drug effects , Mice , Iridium/chemistry , Iridium/pharmacology , Graphite/chemistry , Graphite/pharmacology , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Nitrogen Compounds
14.
J Am Heart Assoc ; 13(9): e032067, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38700010

ABSTRACT

BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.


Subject(s)
Antibiotics, Antineoplastic , Carbon Monoxide , Cardiotoxicity , Doxorubicin , Membrane Proteins , Animals , Doxorubicin/toxicity , Carbon Monoxide/metabolism , Antibiotics, Antineoplastic/toxicity , Female , Administration, Oral , Mice , Heme Oxygenase-1/metabolism , Heart Diseases/chemically induced , Heart Diseases/prevention & control , Heart Diseases/metabolism , Heart Diseases/pathology , Disease Models, Animal , Mice, Inbred C57BL , Carboxyhemoglobin/metabolism , Ventricular Function, Left/drug effects , Humans
15.
J Chem Inf Model ; 64(10): 4193-4203, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38728115

ABSTRACT

[NiFe] hydrogenases can act as efficient catalysts for hydrogen oxidation and biofuel production. However, some [NiFe] hydrogenases are inhibited by gas molecules present in the environment, such as O2 and CO. One strategy to engineer [NiFe] hydrogenases and achieve O2- and CO-tolerant enzymes is by introducing point mutations to block the access of inhibitors to the catalytic site. In this work, we characterized the unbinding pathways of CO in the complex with the wild-type and 10 different mutants of [NiFe] hydrogenase from Desulfovibrio fructosovorans using τ-random accelerated molecular dynamics (τRAMD) to enhance the sampling of unbinding events. The ranking provided by the relative residence times computed with τRAMD is in agreement with experiments. Extensive data analysis of the simulations revealed that from the two bottlenecks proposed in previous studies for the transit of gas molecules (residues 74 and 122 and residues 74 and 476), only one of them (residues 74 and 122) effectively modulates diffusion and residence times for CO. We also computed pathway probabilities for the unbinding of CO, O2, and H2 from the wild-type [NiFe] hydrogenase, and we observed that while the most probable pathways are the same, the secondary pathways are different. We propose that introducing mutations to block the most probable paths, in combination with mutations to open the main secondary path used by H2, can be a feasible strategy to achieve CO and O2 resistance in the [NiFe] hydrogenase from Desulfovibrio fructosovorans.


Subject(s)
Hydrogenase , Molecular Dynamics Simulation , Hydrogenase/metabolism , Hydrogenase/chemistry , Hydrogenase/antagonists & inhibitors , Carbon Monoxide/metabolism , Desulfovibrio/enzymology , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Mutation , Oxygen/metabolism , Protein Conformation
16.
Biomaterials ; 309: 122606, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38776593

ABSTRACT

Carbon monoxide (CO) has emerged as a potential antitumor agent by inducing the dysfunction of mitochondria and the apoptosis of cancer cells. However, it remains challenging to deliver appropriate amount of CO into tumor to ensure efficient tumor growth suppression with minimum side effects. Herein we developed a CO prodrug-loaded nanomedicine based on the self-assembly of camptothecin (CPT) polyprodrug amphiphiles. The polyprodrug nanoparticles readily dissociate upon exposure to endogenous H2O2 in the tumor, resulting in rapid release of CPT and generation of high-energy intermediate dioxetanedione. The latter can transfer the energy to neighboring CO prodrugs to activate CO production by chemiexcitation, while CPT promotes the generation of H2O2 in tumors, which in turn facilitates cascade CPT and CO release. As a result, the polyprodrug nanoparticles display remarkable tumor suppression in both subcutaneous and orthotopic breast tumor-bearing mice owing to the self-augmented CPT release and CO generation. In addition, no obvious systemic toxicity was observed in mice treated with the metal-free CO prodrug-loaded nanomedicine, suggesting the good biocompatibility of the polyprodrug nanoparticles. Our work provides new insights into the design and construction of polyprodrug nanomedicines for synergistic chemo/gas therapy.


Subject(s)
Camptothecin , Carbon Monoxide , Nanomedicine , Nanoparticles , Prodrugs , Animals , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/therapeutic use , Nanomedicine/methods , Camptothecin/pharmacology , Camptothecin/therapeutic use , Camptothecin/administration & dosage , Camptothecin/chemistry , Female , Humans , Carbon Monoxide/chemistry , Nanoparticles/chemistry , Cell Line, Tumor , Mice, Inbred BALB C , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Hydrogen Peroxide/chemistry , Mice, Nude
17.
Microb Biotechnol ; 17(4): e14452, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38568755

ABSTRACT

Gas fermentation of CO2 and H2 is an attractive means to sustainably produce fuels and chemicals. Clostridium autoethanogenum is a model organism for industrial CO to ethanol and presents an opportunity for CO2-to-ethanol processes. As we have previously characterized its CO2/H2 chemostat growth, here we use adaptive laboratory evolution (ALE) with the aim of improving growth with CO2/H2. Seven ALE lineages were generated, all with improved specific growth rates. ALE conducted in the presence of 2% CO along with CO2/H2 generated Evolved lineage D, which showed the highest ethanol titres amongst all the ALE lineages during the fermentation of CO2/H2. Chemostat comparison against the parental strain shows no change in acetate or ethanol production, while Evolved D could achieve a higher maximum dilution rate. Multi-omics analyses at steady state revealed that Evolved D has widespread proteome and intracellular metabolome changes. However, the uptake and production rates and titres remain unaltered until investigating their maximum dilution rate. Yet, we provide numerous insights into CO2/H2 metabolism via these multi-omics data and link these results to mutations, suggesting novel targets for metabolic engineering in this bacterium.


Subject(s)
Carbon Dioxide , Clostridium , Proteome , Carbon Dioxide/metabolism , Carbon Monoxide/metabolism , Hydrogen/metabolism , Fermentation , Ethanol/metabolism , Metabolome
18.
BMC Pulm Med ; 24(1): 163, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570751

ABSTRACT

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.


Subject(s)
Genome-Wide Association Study , Idiopathic Pulmonary Fibrosis , Humans , Smoking/adverse effects , Smoking/genetics , Tobacco Smoking , Idiopathic Pulmonary Fibrosis/genetics , Carbon Monoxide
19.
Undersea Hyperb Med ; 51(1): 37-40, 2024.
Article in English | MEDLINE | ID: mdl-38615351

ABSTRACT

Carbon monoxide (CO) and cyanide poisoning are frequent causes of morbidity and mortality in cases of house and industrial fires. The 14th edition of guidelines from the Undersea and Hyperbaric Medical Society does not recommend hyperbaric oxygen (HBO2) treatment in those patients who have suffered a cardiac arrest and had to receive cardiopulmonary resuscitation. In this paper, we describe the case of a 31-year-old patient who received HBO2 treatment in the setting of cardiac arrest and survived.


Subject(s)
Carbon Monoxide Poisoning , Heart Arrest , Hyperbaric Oxygenation , Humans , Adult , Carbon Monoxide Poisoning/complications , Carbon Monoxide Poisoning/therapy , Heart Arrest/etiology , Heart Arrest/therapy , Oxygen , Carbon Monoxide
20.
Biol Pharm Bull ; 47(4): 868-871, 2024.
Article in English | MEDLINE | ID: mdl-38644197

ABSTRACT

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.


Subject(s)
Carbon Monoxide , Inflammation , Muscle, Skeletal , Rats, Sprague-Dawley , Reperfusion Injury , Animals , Reperfusion Injury/drug therapy , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Male , Inflammation/drug therapy , Erythrocytes/drug effects , Erythrocytes/metabolism , Rats , Creatine Kinase/blood , Hindlimb/blood supply , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Interleukin-6/metabolism , Interleukin-6/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...