A BODIPY-Ferrocene Conjugate for the Combined Photodynamic Therapy and Chemodynamic Therapy with Improved Antitumor Efficiency.

Photodynamic therapy (PDT) can destroy tumor cells by generating singlet oxygen (1O2) under light irradiation, which is limited by the hypoxia of the neoplastic tissue. Chemodynamic therapy (CDT) can produce toxic hydroxyl radical (•OH) to eradicate tumor cells by catalytic decomposition of endogenous hydrogen peroxide (H2O2), the therapeutic effect of which is highly dependent on the concentration of H2O2. Herein, we propose a BODIPY-ferrocene conjugate with a balanced 1O2 and •OH generation capacity, which can serve as a high-efficiency antitumor agent by combining PDT and CDT. The ferrocene moieties endow the as-prepared conjugates with the ability of chemodynamic killing of tumor cells. Moreover, combined PDT/CDT therapy with improved antitumor efficiency can be realized after exposure to light irradiation. Compared with the monotherapy by PDT or CDT, the BODIPY-ferrocene conjugates can significantly increase the intracellular ROS levels of the tumor cells after light irradiation, thereby inducing the tumor cell apoptosis at low drug doses. In this way, a synergistic antitumor treatment is achieved by the combination of PDT and CDT.

Microplastics supply contaminants in food chain: non-negligible threat to health safety.

The occurrence of microplastics (MPs) and organic pollutants (OPs) residues is commonly observed in diverse environmental settings, where their interactions can potentially alter the behavior, availability, and toxicity of OPs, thereby posing risks to ecosystems. Herein, we particularly emphasize the potential for bioaccumulation and the biomagnification effect of MPs in the presence of OPs within the food chain. Despite the ongoing influx of novel information, there exists a dearth of data concerning the destiny and consequences of MPs in the context of food pollution. Further endeavors are imperative to unravel the destiny and repercussions of MPs/OPs within food ecosystems and processing procedures, aiming to gain a deeper understanding of the joint effect on human health and food quality. Nevertheless, the adsorption and desorption behavior of coexisting pollutants can be significantly influenced by MPs forming biofilms within real-world environments, including temperature, pH, and food constituents. A considerable portion of MPs tend to accumulate in the epidermis of vegetables and fruits, thus necessitating further research to comprehend the potential ramifications of MPs on the infiltration behavior of OPs on agricultural product surfaces.

Impacts of Perfluoroalkyl Substances on Aqueous and Nonaqueous Phase Liquid Dechlorination by Sulfidized Nanoscale Zerovalent Iron.

Per- and poly fluoroalkyl substances (PFASs) are often encountered with nonaqueous phase liquid (NAPL) in the groundwater at fire-fighting and military training sites. However, it is unclear how PFASs affect the dechlorination performance of sulfidized nanoscale zerovalent iron (S-nFe0), which is an emerging promising NAPL remediation agent. Here, S-nFe0 synthesized with controllable S speciation (FeS or FeS2) were characterized to assess their interactions with PFASs and their dechlorination performance for trichloroethylene NAPL (TCE-NAPL). Surface-adsorbed PFASs blocked materials' reactive sites and inhibited aqueous TCE dechlorination. In contrast, PFASs-adsorbed particles with improved hydrophobicity tended to enrich at the NAPL-water interface, and the reactive sites were re-exposed after the PFASs accumulation into the NAPL phase to accelerate dechlorination. This PFASs-induced phenomenon allowed the materials to present a higher reactivity (up to 1.8-fold) with a high electron efficiency (up to 99%) for TCE-NAPL dechlorination. Moreover, nFe0-FeS2 with a higher hydrophobicity was more readily enriched at the NAPL-water interface and more reactive and selective than nFe0-FeS, regardless of coexisting PFASs. These results unveil that a small amount of yet previously overlooked coexisting PFASs can favor selective reductions of TCE-NAPL by S-nFe0, highlighting the importance of materials hydrophobicity and transportation induced by S and PFASs for NAPL remediation.

Ferric Oxide Nanomaterials and Plant-Rhizobacteria Symbionts Cogenerate Iron Plaque for Removing Highly Chlorinated Contaminants in Dryland Soils.

Rhizosphere iron plaques derived from Fe-based nanomaterials (NMs) are a promising tool for sustainable agriculture. However, the requirement for flooded conditions to generate iron plaque limits the scope of the NM application. In this study, we achieved in situ Fenton oxidation of a highly chlorinated persistent organic pollutant (2,2',4,5,5'-pentachlorobiphenyl, PCB101) through iron plaque mediated by the interaction between α-Fe2O3 NMs and plant-rhizobacteria symbionts under dryland conditions. Mechanistically, the coexistence of α-Fe2O3 NMs and Pseudomonas chlororaphis JD37 stimulated alfalfa roots to secrete acidic and reductive agents as well as H2O2, which together mediated the rhizosphere Fenton reaction and converted α-Fe2O3 NMs into iron plaque rich in Fe(II)-silicate. Further verifications reproduced the Fenton reaction in vitro using α-Fe2O3 NMs and rhizosphere compounds, confirming the critical role of •OH in the oxidative degradation of PCB101. Significant reductions in PCB101 content by 18.6%, 42.9%, and 23.2% were respectively found in stem, leaf, and soil after a 120-d treatment, proving the effectiveness of this NMs-plant-rhizobacteria technique for simultaneously safe crop production and soil remediation. These findings can help expand the potential applications of nanobio interaction and its mediated iron plaque generation for both agricultural practice and soil remediation.

Distribution pattern analysis of multiple antibiotics in the soil-rice system using a QuEChERS extraction method.

Antibiotics are commonly released into paddy fields as mixtures via human activities. However, the simultaneous extraction and detection of these chemicals from multiple media are technically challenging due to their different physicochemical properties, resulting in unclear patterns of their transport in the soil-rice system. In this study, a "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) method was developed for the simultaneous analysis of 4 tetracyclines (TCs) and 4 fluoroquinolones (FQs) in the soil and rice tissues from a local poultry farm, and thereby the distribution patterns of the target antibiotics in the soil-rice system and their risk levels to the soil were analyzed. After parameter optimization, the calibration range used for the target antibiotics was 0.1-50 µg/L and each calibration curve was linear with a coefficient of determination (R2 > 0.995); The QuEChERS method achieved satisfactory recovery rates (70.3-124.6%) along with sensitive detection limits (0.005-0.21 ng/g) for TCs and FQs in the soil, root, stem, leaf, and grain. Among the 8 antibiotics, enrofloxacin (ENX), ciprofloxacin (CIP), oxytetracycline (OTC), and doxycycline (DOX) were detected around a poultry farm. The four antibiotics in the collected paddy soils around the poultry farm ranged from 7.1 ng/g to 395.5 ng/g. Notably, ENX and DOX had higher ecological risks (risk quotient values >1) than CIP and OTC in soil. ENX, CIP, and DOX were highly enriched in rice roots with concentrations up to 471.9, 857.3, and 547.4 ng/g, respectively, which were also detected in rice aboveground tissues. The findings may provide both technical and practical guidance for the understanding of antibiotic environmental behavior and risks.

The effects of nanoplastics and microcystin-LR coexposure on Aristichthys nobilis at the early developmental stages.

Nanoplastics (NPs) and microcystin-LR (MC-LR) are two common and harmful pollutants in water environments, especially at aquafarm where are full of plastic products and algae. It is of great significance to study the toxic effects and mechanisms of the NPs and/or MC-LR on fish at the early stage. In this study, the embryo and larvae of a filtering-feeding fish, Aristichthys nobilis, were used as the research objects. The results showed that the survival and hatching rates of the embryo were not significantly affected by the environmental concentration exposure of these two pollutants. Scanning electron microscopy (SEM) observation displayed that NPs adhered to the surface of the embryo membrane. Transcriptomic and bioinformatic analyses revealed that the NPs exposure activated neuromuscular junction development and skeletal muscle fiber in larvae, and affected C5-Branched dibasic acid metabolism. The metabolic and biosynthetic processes of zeaxanthin, xanthophyll, tetraterpenoid, and carotenoid were suppressed after the MC-LR exposure, which was harmful to the retinol metabolism of fish. Excessive production of superoxide dismutase (SOD) was detected under the MC-LR exposure. The MC-LR and NPs coexposure triggered primary immunodeficiency and adaptive immune response, leading to the possibility of reduced fitness of A.nobilis during the development. Collectively, our results indicate that environmental concentration NPs and MC-LR coexposure could cause toxic damage and enhance sick risk in A.nobilis, providing new insights into the risk of NPs and MC-LR on filtering-feeding fish.

Needs and Constraints for Cardiac Rehabilitation Among Patients with Coronary Heart Disease Within a Community-Based Setting: A Study Based on Focus Group Interviews.

Objective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population. Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi's method of descriptive data analysis. Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) "Insufficient CR resources for patients": Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) "Patient CR initiative": Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise. Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.

Phosphodiesterase 5A regulates the vomeronasal pump in mice.

The vomeronasal organ (VNO) is a specialized chemoreceptive structure in many vertebrates that detects chemical stimuli, mostly pheromones, which often elicit innate behaviors such as mating and aggression. Previous studies in rodents have demonstrated that chemical stimuli are actively transported to the VNO via a blood vessel-based pumping mechanism, and this pumping mechanism is necessary for vomeronasal stimulation in behaving animals. However, the molecular mechanisms that regulate the vomeronasal pump remain mostly unknown. In this study, we observed a high level of expression of phosphodiesterase 5A (PDE5A) in the vomeronasal blood vessel of mice. We provided evidence to support the potential role of PDE5A in vomeronasal pump regulation. Local application of PDE5A inhibitors-sildenafil or tadalafil-to the vomeronasal organ (VNO) reduced stimulus delivery into the VNO, decreased the pheromone-induced activity of vomeronasal sensory neurons, and attenuated male-male aggressive behaviors. PDE5A is well known to play a role in regulating blood vessel tone in several organs. Our study advances our understanding of the molecular regulation of the vomeronasal pump.

Origin of the Activity of Electrochemical Ozone Production Over Rutile PbO2 Surfaces.

Ozonation water treatment technology has attracted increasing attention due to its environmental benign and high efficiency. Rutile PbO2 is a promising anode material for electrochemical ozone production (EOP). However, the reaction mechanism underlying ozone production catalyzed by PbO2 was rarely studied and not well-understood, which was in part due to the overlook of the electrochemistry-driven formation of oxygen vacancy (OV) of PbO2. Herein, we unrevealed the origin of the EOP activity of PbO2 starting from the electrochemical surface state analysis using density functional theory (DFT) calculations, activity analysis, and catalytic volcano modeling. Interestingly, we found that under experimental EOP potential (i. e., a potential around 2.2 V vs. reversible hydrogen electrode), OV can still be generated easily on PbO2 surfaces. Our subsequent kinetic and thermodynamic analyses show that these OV sites on PbO2 surfaces are highly active for the EOP reaction through an interesting atomic oxygen (O*)-O2 coupled mechanism. In particular, rutile PbO2(101) with the "in-situ" generated OV exhibited superior EOP activities, outperforming the (111) and (110) surfaces. Finally, by catalytic volcano modeling, we found that PbO2 is close to the theoretical optimum of the reaction, suggesting a superior EOP performance of rutile PbO2. All these analyses are in good agreement with previous experimental observations in terms of EOP overpotentials. This study provides the first volcano model to explain why rutile PbO2 is among the best metal oxide materials for EOP and provides new design guidelines for this rarely studied but industrially promising reaction.

Preparation and measurement of a sandwiched Sn atomic beam source for laser resonance ionization mass spectrometry.

Isotope analysis of Sn plays a crucial role in geochemical studies and in monitoring nuclear contamination. Nevertheless, prevalent analytical techniques for examining Sn isotopes encounter the issue of isobaric interference, markedly impacting the accuracy of the test results. Laser resonance ionization mass spectrometry (LRIMS) can effectively overcome the difficulties associated with the isobaric interference inherent in commercial mass spectrometry. In this paper, different amounts of Sn were prepared on Re filaments by electrodeposition and tested via LRIMS. The results showed that the average detection efficiency of LRIMS decreased with increasing total Sn content from 1 µg to 4 µg, and the fluctuations in the test results among the samples increased significantly. Therefore, the electrodeposition process, as well as the composition and morphology of the deposits were characterized by SEM, EDS and XPS; results showed that the degradation of the samples with increasing Sn content was attributed to the complexity of the composition, micro-structure, valence of the deposits, and the interference of various elements. To cope with the anomalies encountered above, the deposits were heat-treated at 600 °C in a hydrogen atmosphere to eliminate detrimental impurities, like Cl, and Sn was effectively reduced to an almost singular atomic state. Furthermore, a titanium layer was covered on the surface of the heat-treated deposit by magnetron sputtering. Ultimately, a highly efficient and stable Sn atomic beam source with a sandwiched structure has been successfully developed and exhibits broad application prospect.

Nucleophilic hydrolysis enables HF-etched MXene kilofarad specific capacitance and excellent rate performance.

Here, an unusual MXene with a high ratio of oxygen functional groups was prepared by hydrothermal treatment of HF-etched MXene in aqueous KOH solution. The prepared MXene (H-220) exhibits ultrahigh specific capacitance (1030 F g-1 in a potential window of 0.85 V), and excellent rate and cycling performance simultaneously in a sulfuric acid electrolyte, and can act as an anode material of proton batteries.

Rapid Defect Engineering in FeCoNi/FeAl2O4 Hybrid for Enhanced Oxygen Evolution Catalysis: A Pathway to High-Performance Electrocatalysts.

Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in the FeCoNi/FeAl2O4 hybrid coating, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300 mA cm-2 for over 120 hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect-engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.

Supramolecularly modulated carbon-centered radicals: toward selective oxidation from benzyl alcohol to aldehyde.

The reactivity of ketyl radicals and benzoyl radicals, two key intermediates of photo-induced oxidation of benzyl alcohol, can be stabilized by the host-guest interaction of the radicals with cucurbit[7]uril. As a result, the selectivity of photo-induced oxidation from benzyl alcohol to aldehyde is significantly improved by diminishing side reactions and inhibiting the generation of carboxylic acid products. This work presents a new route to modulate the reactivity of radical intermediates, enriching the chemistry of supramolecular intermediates and the toolbox of supramolecular catalysis.

Redox potential model for guiding moderate oxidation of polycyclic aromatic hydrocarbons in soils.

In-situ chemical oxidation is an important approach to remediate soils contaminated with persistent organic pollutants, e.g., polycyclic aromatic hydrocarbons (PAHs). However, massive oxidants are added into soils without an explicit model for predicting the redox potential (Eh) during soil remediation, and overdosed oxidants would pose secondary damage by disturbing soil organic matter and acidity. Here, a soil redox potential (Eh) model was first established to quantify the relationship among oxidation parameters, crucial soil properties, and pollutant elimination. The impacts of oxidant types and doses, soil pH, and soil organic carbon contents on soil Eh were systematically clarified in four commonly used oxidation systems (i.e., KMnO4, H2O2, fenton, and persulfate). The relative error of preliminary Eh model was increased from 48-62% to 4-16% after being modified with the soil texture and dissolved organic carbon, and this high accuracy was verified by 12 actual PAHs contaminated soils. Combining the discovered critical oxidation potential (COP) of PAHs, the moderate oxidation process could be regulated by the guidance of the soil Eh model in different soil conditions. Moreover, the product analysis revealed that the hydroxylation of PAHs occurred most frequently when the soil Eh reached their COP, providing a foundation for further microorganism remediation. These results provide a feasible strategy for selecting oxidants and controlling their doses toward moderate oxidation of contaminated soils, which will reduce the consumption of soil organic matter and protect the main structure and function of soil for future utilization. ENVIRONMENTAL IMPLICATIONS: This study provides a novel insight into the moderate chemical oxidation by the Eh model and largely reduces the secondary risks of excessive oxidation and oxidant residual in ISCO. The moderate oxidation of PAHs could be a first step to decrease their toxicity and increase their bioaccessibility, favoring the microbial degradation of PAHs. Controlling the soil Eh with the established model here could be a promising approach to couple moderate oxidation of organic contaminants with microbial degradation. Such an effective and green soil remediation will largely preserve the soil's functional structure and favor the subsequent utilization of remediated soil.

Nanoplastics inhibit carbon fixation in algae: The effect of aging.

Despite the considerable efforts devoted to the toxicological assessment of nanoplastics, the effect of UV-irradiation induced aging, a realistic environmental process, on the toxicity of nanoplastics toward microalgae and its underlying mechanisms remain largely unknown. Herein, this study comparatively investigated the toxicities of polystyrene nanoplastics (nano-PS) and the UV-aged nano-PS on the eukaryotic alga Chlorella vulgaris, focusing on evaluating their inhibitory effects on carbon fixation. Exposure to environmentally relevant concentrations (0.1-10 mg/L) of nano-PS caused severe damage to chloroplast, inhibited the photosynthetic efficiency and electron transport, and suppressed the activities of carbon fixation related enzymes. Multi-omics results revealed that nano-PS interfered with energy supply by disrupting light reactions and TCA cycle and hindered the Calvin cycle, thereby inhibiting the photosynthetic carbon fixation of algae. The above alterations partially recovered after a recovery period. The aged nano-PS were less toxic than the pristine ones as evidenced by the mitigated inhibitory effect on algal growth and carbon fixation. The aging process introduced oxygen-containing functional groups on the surface of nano-PS, increased the hydrophilicity of nano-PS, limited their attachment on algal cells, and thus reduced the toxicity. The findings of this work highlight the potential threat of nanoplastics to the global carbon cycle.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

Study on the influence of pore water pressure on shear mechanical properties and fracture surface morphology of sandstone.

To further investigate the weakening effect of pore water pressure on intact rock mechanics properties and characteristics of fracture surface after failure, direct shear tests of sandstone were conducted under different pore pressure. A 3D scanner was employed to digitize the morphology of the post-shear fracture surface. The variogram function was applied to quantify the anisotropic characteristics of post-shear fracture surface. The relationship between deformation during shear failure of intact rock and quantitative parameters of fracture surface after shear failure was initially established. It can be found that amplitudes of the sinusoidal surface determine the maximum value of variogram, and period affect lag distance that reach the maximum value of variogram. Test results revealed that the increase of pore pressure has obvious weakening effect on shear strength and deformation of rock. Moreover, the increase of pore pressure makes the shear fracture surface flatter. It can be obtained that both Sillmax and Rangemax are positively related to shear strain, but negatively related to normal strain.

Targeted Gene Deletion or Antagonism of the Prostaglandin E2 EP3 Receptor Protects Against Cardiac Injury Postmyocardial Infarction.

BACKGROUND: Prostaglandin E2 acts through 4 G-protein-coupled receptors (EP1-EP4). We previously reported that activation of the EP3 receptor reduces cardiac contractility, and its expression increases after a myocardial infarction (MI), mediating the reduction in cardiac function. In contrast, cardiac overexpression of the EP4 receptor in MI substantially improves cardiac function. Moreover, we recently reported that mice overexpressing EP3 have heart failure under basal conditions and worsened cardiac function after MI. Thus, the deleterious effects of the prostaglandin E2 EP receptors in the heart are mediated via its EP3 receptor. We, therefore, hypothesized that cardiomyocyte-specific knockout (CM-EP3 KO) or antagonism of the EP3 receptor protects the heart after MI. METHODS: To test our hypothesis, we made the novel CM-EP3 KO mouse and subjected CM-EP3 KO or controls to sham or MI surgery for 2 weeks. In separate experiments, C57BL/6 mice were subjected to 2 weeks of MI and treated with either the EP3 antagonist L798 106 or vehicle starting 3 days post-MI. RESULTS: CM-EP3 KO significantly prevented a decline in cardiac function after MI compared with WT animals and prevented an increase in hypertrophy and fibrosis. Excitingly, mice treated with L798 106 3 days after MI had significantly better cardiac function compared with vehicle-treated mice. CONCLUSIONS: Altogether, these data suggest that EP3 may play a direct role in regulating cardiac function, and pharmaceutical targeting of the EP3 receptor may be a therapeutic option in the treatment of heart failure.