Deficiency of inflammation-sensing protein neuropilin-2 in myeloid-derived macrophages exacerbates colitis via NF-κB activation.

Neuropilin-2 (NRP2) is a multifunctional protein engaged in the regulation of angiogenesis, lymphangiogenesis, axon guidance, and tumor metastasis, but its function in colitis remains unclear. Here, we found that NRP2 was an inflammation-sensing protein rapidly and dramatically induced in myeloid cells, especially in macrophages, under inflammatory contexts. NRP2 deficiency in myeloid cells exacerbated dextran sulfate sodium salt-induced experimental colitis by promoting polarization of M1 macrophages and colon injury. Mechanistically, NRP2 could be induced via NF-κB activation by TNF-α in macrophages, but exerted an inhibitory effect on NF-κB signaling, forming a negative feedback loop with NF-κB to sense and alleviate inflammation. Deletion of NRP2 in macrophages broke this negative feedback circuit, leading to NF-κB overactivation, inflammatory exacerbation, and more severe colitis. Collectively, these findings reveal inflammation restriction as a role for NRP2 in macrophages under inflammation contexts and suggest that NRP2 in macrophages may relieve inflammation in inflammatory bowel disease. © 2023 The Pathological Society of Great Britain and Ireland.

Pure Silica with Ordered Silanols for Propylene/Propane Adsorptive Separation Unraveled by Three-Dimensional Electron Diffraction.

Adsorptive separation of propylene (C3H6) from propane (C3H8), which could deal with energy-intensive cryogenic distillation technologies, remains challenging due to their similar physiochemical properties. Herein, we present a pure silica zeolite with ordered silanols (OSs), whose crystallographic structure was unraveled by the advanced three-dimensional electron diffraction (3D ED), displaying the highly efficient separation of propylene from propane under ambient conditions. The 3D ED technique enables us to investigate its 8-ring pore opening transformation from the round one to the elliptical one during the removal of organic structure-directing agents. Such unique elliptical 8-ring pore openings can exclude larger-size propane and only adsorb propylene. Its C3H6/C3H8 separation performance is also confirmed by column breakthrough experiments, showing a high dynamic adsorption capacity of 53.36 cm3 g-1 for C3H6 but negligible C3H8 under ambient conditions. The dynamic capacity for C3H6 is superior to that of the well-known pure silica DDR-type zeolite (31.07 cm3 g-1). The density functional theory calculation demonstrates that the adsorbed propylene is distributed in the heart-shaped cavity and has a weak interaction with the OSs.

Synthesis and Visualization of Entangled 3D Covalent Organic Frameworks with High-Valency Stereoscopic Molecular Nodes for Gas Separation.

The structural diversity of three-dimensional (3D) covalent organic frameworks (COFs) are limited as there are only a few choices of building units with multiple symmetrically distributed connection sites. To date, 4 and 6-connected stereoscopic nodes with Td , D3h , D3d and C3 symmetries have been mostly reported, delivering limited 3D topologies. We propose an efficient approach to expand the 3D COF repertoire by introducing a high-valency quadrangular prism (D4h ) stereoscopic node with a connectivity of eight, based on which two isoreticular 3D imine-linked COFs can be created. Low-dose electron microscopy allows the direct visualization of their 2-fold interpenetrated bcu networks. These 3D COFs are endowed with unique pore architectures and strong molecular binding sites, and exhibit excellent performance in separating C2 H2 /CO2 and C2 H2 /CH4 gas pairs. The introduction of high-valency stereoscopic nodes would lead to an outburst of new topologies for 3D COFs.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Enhanced Intracellular Delivery and Tissue Retention of Nanoparticles by Mussel-Inspired Surface Chemistry.

Nanomaterials have been broadly studied for intracellular delivery of diverse compounds for diagnosis or therapy. Currently it remains challenging for discovering new biomolecules that can prominently enhance cellular internalization and tissue retention of nanoparticles (NPs). Herein we report for the first time that a mussel-inspired engineering approach may notably promote cellular uptake and tissue retention of NPs. In this strategy, the catechol moiety is covalently anchored onto biodegradable NPs. Thus, fabricated NPs can be more effectively internalized by sensitive and multidrug resistant tumor cells, as well as some normal cells, resulting in remarkably potentiated in vitro activity when an antitumor drug is packaged. Moreover, the newly engineered NPs afford increased tissue retention post local or oral delivery. This biomimetic approach is promising for creating functional nanomaterials for drug delivery, vaccination, and cell therapy.

[Correlation between cognitive function and hippocampal atrophy and cerebral white matter lesions in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the relationship between cognitive impairment and the changes of hippocampal structure and cerebral white matter on brain magnetic resonance imaging (MRI) in subjects with obstructive sleep apnea hypopnea (OSAHS). METHODS: A total of 81 snoring patients were monitored by overnight polysomnography (PSG) at Sleep Center, Second Affiliated Hospital, Soochow University from March 2012 to August 2013. Based on the results of apnea-hypopnea index (AHI), they were divided into mild (n = 23), moderate (n = 18), severe OSAHS (n = 23) and primary snoring (n = 17) groups. Periventricular hyperintensity (PVH) related to the severity of cerebral white matter lesions and hippocampal atrophy on brain MRI were evaluated according to the Fukudas method and Scheltens standard. The sequences of regular and perpendicular to bilateral hippocampal fluid attenuated inversion recovery (FIAIR) were used. Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) were performed to evaluate the changes of cognitive function in all subjects. RESULTS: The cognitive function scores, especially MoCA, progressively decreased and the scores of hippocampal atrophy and PVH increased as the severity of OSAHS aggravated among these groups. Compared to primary snoring group, MoCA and MMSE scores decreased (24.5 ± 2.7 vs 28.0 ± 1.9, P = 0.000; 27.5 ± 1.4 vs 28.7 ± 1.3, P = 0.013) and hippocampal atrophy and PVH scores increased (2.4 ± 1.2 vs 1.5 ± 1.2, P = 0.007; 3.6 ± 1.0 vs 1.6 ± 1.5, P = 0.000) in the severe OSAHS group. The evaluations of MoCA subdomains further revealed selective reduction in visual space, execution function and delayed memory. PVH scores and hippocampal atrophy scores were negatively correlated with MoCA scores (r = -0.30, P = 0.010; r = -0.30, P = 0.006). Multiple linear regression analysis indicated that the degrees of AHI and hippocampal atrophy were the major risk factors for MoCA scores (standardized regression coefficient: -0.386, -0.247; P = 0.000, 0.020). The scores of hippocampal atrophy and PVH were positively correlated with AHI, oxygen reduction index (ODI) and respiratory related arousal index (RI) and negatively with minimum oxygen saturation (LSaO2) and average oxygen saturation (MSaO2) (P < 0.05). CONCLUSIONS: The changes of MRI in hippocampus and cerebral white matter are closely related with cognitive dysfunction. And it may become an objective indicator of assessing cognitive function in OSAHS patients.

Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.

Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages. The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.

[Injury repairing and magnetic resonance tracing of transplanted bone marrow stromal cells in rat liver with hepatic fibrosis].

OBJECTIVE: To explore the recurring patterns of migration and distribution of transplanted bone marrow stromal cells (BMSCs) in rat model with hepatic fibrosis and the feasibility of magnetic resonance (MR) tracing. METHODS: BMSCs labeled with 5-bromodeoxyuridine (Brdu) and super para-magnetic iron oxide (SPIO) were transplanted into rat model with hepatic fibrosis via portal vein. MR scan was performed at Hour 2, Day 3, Day 7 and Week 2 post-transplantation to analyze the hepatic features of MR signal intensity and pathohistology of BMSCs. RESULTS: Multiple hypo-intense lesions appeared in hepatic hilar region at Hour 2 and became smaller with the elapsing time. Hemosiderin and Brdu immunohistochemical stains showed that positive cells were found in portal vein of hepatic porta at Hour 2, small branches of portal vein, sinus hepaticus and around central veins of hepatic lobules at Day 3 and liver parenchyma (esp. in area of lesion) at Day 7 and Week 2. Some of transplanted BMSCs were tightly connected with liver cell to form liver cell cord. The signal intensity changes of MRI corresponded to histological findings at different timepoints. CONCLUSION: The transplanted BMSCs are gradually scattered in whole liver (esp. in lesion area) so that it may help to repair hepatic lesions. And the recurring patterns of MR signal intensity changes reflected the condition of distribution, immigration and differentiation of transplanted cells.

[Values of magnetic resonance spectrum imaging in the diagnosis of hepatic fibrosis of rats].

OBJECTIVE: To explore the values of magnetic resonance spectrum (MRS) in early diagnosis, quantization analysis and staging of hepatic fibrosis. METHODS: A rat model of hepatic fibrosis was established by the method of carbon tetra carbon (CCl4). A total of 47 SD rats were divided into model (n = 40) and control (n = 7) groups. 1H-MRS was performed. The model rats of hepatic fibrosis were grouped according to their pathological stages. The ratio of peak height and peak area of metabolites and lipid (Cho/Lip, Glx/Lip, Lac/Lip and Cr/Lip) were calculated and compared respectively. RESULTS: The ratios of peak height of metabolites and lipid were as follows: ratio of Cho and Lip: significant differences existed between control and grades 3 and 4 model groups (P < 0.05); ratio of Glx and Lip: significant differences existed between control and grades 2, 3 and 4 model groups (P < 0.05); ratio of Cr and Lip: significant differences existed between control and grade 3 model groups (P < 0.05). The peak area ratio of main metabolites and lipid of liver were as follows: ratio of Cho and Lip: significant differences existed between control and grade 4 model groups (P < 0.05); ratio of Glx and Lip: significant differences existed between control and other groups (P < 0.05); ratio of Cr and Lip: significant differences existed between control and grade 4 model groups (P < 0.05); ratio of Lac and Lip: no significant differences existed between these groups (P > 0.05). CONCLUSION: The ratios of peak height and peak area of Cho/Lip, Glx/Lip and Cr/Lip are important for the staging of hepatic fibrosis.

Nickel-Catalyzed Enantioselective Dearomative Heck-Reductive Allylic Defluorination Reaction of Indoles.

Herein, we describe a nickel-catalyzed asymmetric dearomative aryl-difluoroallylation reaction of indoles with α-trifluoromethyl alkenes as an electrophilic coupling partner. The reaction proceeds via a cascade sequence involving dearomative Heck cyclization and reductive allylic defluorination. A series of gem-difluoroallyl substituted indolines are obtained in moderate to good yields (36-77% yield) with excellent enantioselectivity (up to 99% ee). The reaction features broad functional group tolerance, scaled-up synthesis, and late-stage diversification.

Pd-Catalyzed Intramolecular Dearomative [4 + 2] Cycloaddition of Naphthalenes with Arylalkynes.

A Pd-catalyzed intramolecular dearomative [4 + 2] cycloaddition reaction of naphthalenes with arylalkynes is developed. The protocol provides a straightforward method to access a range of polycyclic dihydronaphthalenes containing two vicinal all-carbon stereocenters in moderate yields under mild conditions in an air atmosphere. The deuterium labeling experiment suggests a pathway involving electrophilic dearomatization followed by Friedel-Crafts cyclization. Several synthetic transformations of the product were conducted to demonstrate the utility of this reaction.

Bioinspired and Biomimetic Nanomedicines for Targeted Cancer Therapy.

Undesirable side effects and multidrug resistance are the major obstacles in conventional chemotherapy towards cancers. Nanomedicines provide alternative strategies for tumor-targeted therapy due to their inherent properties, such as nanoscale size and tunable surface features. However, the applications of nanomedicines are hampered in vivo due to intrinsic disadvantages, such as poor abilities to cross biological barriers and unexpected off-target effects. Fortunately, biomimetic nanomedicines are emerging as promising therapeutics to maximize anti-tumor efficacy with minimal adverse effects due to their good biocompatibility and high accumulation abilities. These bioengineered agents incorporate both the physicochemical properties of diverse functional materials and the advantages of biological materials to achieve desired purposes, such as prolonged circulation time, specific targeting of tumor cells, and immune modulation. Among biological materials, mammalian cells (such as red blood cells, macrophages, monocytes, and neutrophils) and pathogens (such as viruses, bacteria, and fungi) are the functional components most often used to confer synthetic nanoparticles with the complex functionalities necessary for effective nano-biointeractions. In this review, we focus on recent advances in the development of bioinspired and biomimetic nanomedicines (such as mammalian cell-based drug delivery systems and pathogen-based nanoparticles) for targeted cancer therapy. We also discuss the biological influences and limitations of synthetic materials on the therapeutic effects and targeted efficacies of various nanomedicines.

Reactive Oxygen Species-Responsive and Self-Illuminating Nanoparticles for Inflammation and Tumor Imaging.

Reactive oxygen species (ROS) play a key role in various physiological and pathological processes. Abnormally elevated ROS levels are generally related to the pathogenesis of inflammatory diseases and tumors. Real-time imaging and quantification of ROS can not only provide new insight into mechanistic understanding of diseases associated with ROS but also facilitate high-throughput and high-content drug screening for these diseases. Here, the present protocol introduces ROS-responsive and self-illuminating nanoparticles with chemiluminescence (CL) and fluorescence (FL) properties that can serve as an effective nanoprobe for imaging of pathophysiology, including inflammation and tumor.

Selective and sensitive detection and detoxification of Pd2+ in living cells with a water-soluble fluorescent probe.

Due to the cytotoxic potential of even low doses of Pd2+, the development of its detection and detoxification strategies is highly demanding. In this paper, we developed a water-soluble fluorescent probe IMQU-8 with a new scaffold for Pd2+ sensing. IMQU-8 can detect Pd2+ with high selectivity and sensitivity and has a good detection limit of 2.5 nM under physiological conditions. Its sensing mechanism has been revealed through job plot experiments and HRMS, FT-IR, 1H NMR and DFT calculations, which demonstrated that the N atoms of the pyridyl group and imino group are crucial for Pd2+ sensing. Fluorescence lifetime assessment indicated that IMQU-8 and IMQU-8-Pd have almost identical fluorescence lifetimes, implying that IMQU-8 undergoes static quenching toward Pd2+. Additionally, IMQU-8 has been successfully applied to image Pd2+ in living cells. Since IMQU-8 and its coordinated complex IMQU-8-Pd exhibit low toxicity, IMQU-8 has been applied for the detoxification of Pd2+ in living cells.

Intense infrared emission of Er(3+) in Ca(8)Mg(SiO(4))(4)Cl(2) phosphor from energy transfer of Eu(2+) by broadband down-conversion.

We report on conversion of near-ultraviolet and visible radiation ranging from 250 to 500 nm into near-infrared emission by a Ca(8)Mg(SiO(4))(4)Cl(2): Eu(2+), Er(3+) phosphor. Efficient 1530-1560 nm Er(3+) emission ((4)I(13/2)-->(4)I(15/2)) was detected under the excitation of Eu(2+) (4f?5d) absorption band as a result of energy transfer from Eu(2+) to Er(3+), which is confirmed by both steady state and time-resolved emission spectra. The laser power dependent emission intensity changes were investigated to analysis the energy transfer mechanism. Energy transfer from Eu(2+) to Er(3+) followed by a multi-photon quantum cutting of Er(3+) is proposed. The result indicates that the phosphor has potential application in enhancement of conversion efficient of germanium solar cells because the energy difference of Er(3+): (4)I(13/2)-->(4)I(15/2) transition matches well with the bandgap of Ge (Eg~0.785 eV).

Hydrogen Peroxide-Activatable Nanoparticles for Luminescence Imaging and In Situ Triggerable Photodynamic Therapy of Cancer.

Abnormally increased reactive oxygen species (ROS) are intimately related to the development and metastasis of cancer. Since hydrogen peroxide (H2O2) is a major component of ROS, molecular imaging and selective treatment in response to high H2O2 are intriguing for the management of cancers. Herein, we report novel self-assembly luminescent nanoparticles, which can be activated by H2O2, thereby serving as an effective nanotheranostics for luminescence imaging and in situ photodynamic therapy (PDT) of tumors with high H2O2. This functional nanomedicine was assembled from an amphiphilic conjugate (defined as CLP) based on chlorin e6 (Ce6) simultaneously conjugated with luminol and poly(ethylene glycol), exhibiting a well-defined core-shell nanostructure. Upon triggering by pathologically relevant levels of H2O2, CLP nanoparticles produced luminescence due to the luminol unit and simultaneous excitation of Ce6 by chemiluminescence resonance energy transfer, enabling in vitro and in vivo imaging of tumors with highly expressed H2O2. In addition, excited Ce6 can produce singlet oxygen (1O2) for in situ PDT of H2O2-high tumors and inhibiting lung metastasis, which was demonstrated by in vitro and in vivo experiments. Furthermore, preliminary studies revealed the biosafety of CLP nanoparticles. Consequently, the self-illuminating nanoparticles are promising for noninvasive imaging and therapy of tumors with high expression of H2O2.

A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning.

Accidental or suicidal ingestion of the world's most widely used herbicide, paraquat (PQ), may result in rapid multi-organ failure with a 60% fatality rate due to the absence of an effective detoxification solution. Effective, specific antidotes to PQ poisoning have been highly desired. Methods: The binding constant of PQ and a synthetic receptor, cucurbit[7]uril (CB[7]), was first determined in various pH environments. The antidotal effects of CB[7] on PQ toxicity were firstly evaluated with in-vitro cell lines. With in-vivo mice models, the pharmacokinetics and the biodistribution of PQ in major organs were determined to evaluate the influence of CB[7] on the oral bioavailability of PQ. Major organs' injuries and overall survival rates of the mice were systemically examined to evaluate the therapeutic efficacy of CB[7] on PQ poisoning. Results: We demonstrate that CB[7] may complex PQ strongly under various conditions and significantly reduce its toxicity in vitro and in vivo. Oral administration of PQ in the presence of CB[7] in a mouse model significantly decreased PQ levels in the plasma and major organs and alleviated major organs' injuries, when compared to those of mice administered with PQ alone. Further studies indicated that oral administration of CB[7] within 2 h post PQ ingestion significantly increased the survival rates and extended the survival time of the mice, in contrast to the ineffective treatment by activated charcoal, which is commonly recommended for PQ decontamination. Conclusion: CB[7] may be used as a specific oral antidote for PQ poisoning by strongly binding with PQ and inhibiting its absorption in the gastrointestinal tracts.

An Eco- and User-Friendly Herbicide.

The increasing use of pesticides in agriculture and gardening has caused severe deterioration to both the ecosystem and the health of users (human beings), so there is an urgent need for eco- and user-friendly pesticides. Among a variety of herbicides, paraquat (PQ), frequently used as an effective herbicidal agent worldwide, is well-known for its serious toxicity that has killed, and harmed, thousands of people and countless wildlife such as fish. Herein, we present a facile supramolecular formulation of PQ@cucurbit[7]uril (PQ@CB[7]), prepared by simply mixing PQ with equivalent (molar) CB[7] in water. With addition of CB[7], PQ's cellular uptake was dramatically inhibited. The reactive oxygen species (ROS) generation and the associated apoptosis otherwise induced by PQ in cellular models were both reduced, resulting in increased cellular viability. In a wildtype zebrafish model that is a typical fragile wildlife species in the ecosystem, the supramolecular formulation exhibited significantly reduced hepatotoxicity and increased survival rate, in comparison with those of the fish exposed to free PQ. In a mouse model that is clinically relevant to human being, the administration of PQ@CB[7] significantly alleviated major organ injuries and unusual hematological parameters that were otherwise induced by free PQ, resulting in a significantly increased survival rate. Meanwhile, this formulation maintained effective herbicidal activity that was equivalent to that of free PQ. Taken together, this facile supramolecular PQ formulation is providing not only an extremely rare example of an eco- and user-friendly herbicide that has been desired for decades but also a practical solution for green agriculture.

A self-illuminating nanoparticle for inflammation imaging and cancer therapy.

Nanoparticles have been extensively used for inflammation imaging and photodynamic therapy of cancer. However, the major translational barriers to most nanoparticle-based imaging and therapy applications are the limited depth of tissue penetration, inevitable requirement of external irradiation, and poor biocompatibility of the nanoparticles. To overcome these critical limitations, we synthesized a sensitive, specific, biodegradable luminescent nanoparticle that is self-assembled from an amphiphilic polymeric conjugate with a luminescent donor (luminol) and a fluorescent acceptor [chlorin e6 (Ce6)] for in vivo luminescence imaging and photodynamic therapy in deep tissues. Mechanistically, reactive oxygen species (ROS) and myeloperoxidase generated in inflammatory sites or the tumor microenvironment trigger bioluminescence resonance energy transfer and the production of singlet oxygen (1O2) from the nanoparticle, enabling in vivo imaging and cancer therapy, respectively. This self-illuminating nanoparticle shows an excellent in vivo imaging capability with suitable tissue penetration and resolution in diverse animal models of inflammation. It is also proven to be a selective, potent, and safe antitumor nanomedicine that specifically kills cancer cells via in situ 1O2 produced in the tumor microenvironment, which contains a high level of ROS.

α-Tocopherol preserves cardiac function by reducing oxidative stress and inflammation in ischemia/reperfusion injury.

OBJECTIVE: Myocardial infarction (MI) is a leading cause of mortality and morbidity worldwide and new treatment strategies are highly sought-after. Paradoxically, reperfusion of the ischemic myocardium, as achieved with early percutaneous intervention, results in substantial damage to the heart (ischemia/reperfusion injury) caused by cell death due to aggravated inflammatory and oxidative stress responses. Chronic therapy with vitamin E is not effective in reducing the cardiovascular event rate, presumably through failing to reduce atherosclerotic plaque instability. Notably, acute treatment with vitamin E in patients suffering a MI has not been systematically investigated. METHODS AND RESULTS: We applied alpha-tocopherol (α-TOH), the strongest anti-oxidant form of vitamin E, in murine cardiac ischemia/reperfusion injury induced by ligation of the left anterior descending coronary artery for 60 min. α-TOH significantly reduced infarct size, restored cardiac function as measured by ejection fraction, fractional shortening, cardiac output, and stroke volume, and prevented pathological changes as assessed by state-of-the-art strain and strain-rate analysis. Cardioprotective mechanisms identified, include a decreased infiltration of neutrophils into cardiac tissue and a systemic anti-inflammatory shift from Ly6Chigh to Ly6Clow monocytes. Furthermore, we found a reduction in myeloperoxidase expression and activity, as well as a decrease in reactive oxygen species and the lipid peroxidation markers phosphatidylcholine (PC) (16:0)-9-hydroxyoctadecadienoic acid (HODE) and PC(16:0)-13-HODE) within the infarcted tissue. CONCLUSION: Overall, α-TOH inhibits ischemia/reperfusion injury-induced oxidative and inflammatory responses, and ultimately preserves cardiac function. Therefore, our study provides a strong incentive to test vitamin E as an acute therapy in patients suffering a MI.