Non-invasive paper-based sensors containing rare-earth-doped nanoparticles for the detection of D-glucose.

Today, diabetes mellitus is one of the most common diseases that affects the population on a worldwide scale. Patients suffering from this disease are required to control their blood-glucose levels several times a day through invasive methods such as piercing their fingers. Our NaGdF4: 5% Er3+, 3% Nd3+ nanoparticles demonstrate a remarkable ability to detect D-glucose levels by analysing alterations in their red-to-green ratio, since this sensitivity arises from the interaction between the nanoparticles and the OH groups present in the D-glucose molecules, resulting in discernible changes in the emission of the green and red bands. These luminescent sensors were implemented and tested on paper substrates, offering a portable, low-cost and enzyme-free solution for D-glucose detection in aqueous solutions with a limit of detection of 22 mg/dL. With this, our study contributes to the development of non-invasive D-glucose sensors, holding promising implications for managing diabetes and improving overall patient well-being with possible future applications in D-glucose sensing through tear fluid.

Correlation of Plasmatic Amyloid Beta Peptides (Aß-40, Aß-42) with Myocardial Injury and Inflammatory Biomarkers in Acute Coronary Syndrome.

Background/Objective: Amyloid beta (ß) -40 levels increase with age and inflammation states and appear to be associated with clinical manifestations of acute coronary syndrome (ACS). We investigated the correlation of Aß peptides with myocardial injury and inflammation biomarkers in patients with or without ST elevation myocardial infarction (STEMI, NSTEMI). Methods: This singe-center, cross-sectional, observational, and correlation study included 65 patients with ACS (n = 34 STEMI, 29 males, age = 58 ± 12 years; n = 31 NSTEMI, 22 males, age = 60 ± 12 years) who were enrolled in the coronary care unit within 12 h after symptom onset from February 2022 to May 2023. Aß peptide levels and biochemical parameters were assessed. Results: NSTEMI patients had a higher prevalence of hypertension (p = 0.039), diabetes (p = 0.043), smoking (p = 0.003), and prior myocardial infarction (p = 0.010) compared to STEMI patients. We observed a higher level of Aß-42 in NSTEMI (p = 0.001) but no difference in Aß-40 levels. We also found a correlation between age and NT-proBNP with both Aß peptides (Aß-40, Aß-42) (p = 0.001, p = 0.002 respectively). Conclusions: Our results show that patients with NSTEMI had a higher prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, and prior myocardial infarction). Considering these results, we propose that Aß-42 can add value to risk stratification in NSTEMI patients.

C-Reactive Protein: The Quintessential Marker of Systemic Inflammation in Coronary Artery Disease-Advancing toward Precision Medicine.

Atherosclerotic cardiovascular disease (CVD) remains the leading cause of mortality worldwide. While conventional risk factors have been studied and managed, CVD continues to pose a global threat. Risk scoring systems based on these factors have been developed to predict acute coronary syndromes and guide therapeutic interventions. However, traditional risk algorithms may not fully capture the complexities of individual patients. Recent research highlights the role of inflammation, particularly chronic low-grade inflammation, in the pathogenesis of coronary artery disease (CAD). C-reactive protein (CRP) is an inflammatory molecule that has demonstrated value as a predictive marker for cardiovascular risk assessment, both independently and in conjunction with other parameters. It has been incorporated into risk assessment algorithms, enhancing risk prediction and guiding therapeutic decisions. Pharmacological interventions with anti-inflammatory properties, such as statins, glucagon-like peptide-1 agonists, and interleukin-1 inhibitors, have shown promising effects in reducing both cardiovascular risks and CRP levels. This manuscript provides a comprehensive review of CRP as a marker of systemic inflammation in CAD. By exploring the current knowledge surrounding CRP and its implications for risk prediction and therapeutic interventions, this review contributes to the advancement of personalized cardiology and the optimization of patient care.

Ag2 S Biocompatible Ensembles as Dual OCT Contrast Agents and NIR Ocular Imaging Probes.

Ag2 S nanoparticles (NPs) emerge as a unique system that simultaneously features in vivo near-infrared (NIR) imaging, remote heating, and low toxicity thermal sensing. In this work, their capabilities are extended into the fields of optical coherence tomography (OCT), as contrast agents, and NIR probes in both ex vivo and in vivo experiments in eyeballs. The new dual property for ocular imaging is obtained by the preparation of Ag2 S NPs ensembles with a biocompatible amphiphilic block copolymer. Rather than a classical ligand exchange, where surface traps may arise due to incomplete replacement of surface sites, the use of this polymer provides a protective extra layer that preserves the photoluminescence properties of the NPs, and the procedure allows for the controlled preparation of submicrometric scattering centers. The resulting NPs ensembles show extraordinary colloidal stability with time and biocompatibility, enhancing the contrast in OCT with simultaneous NIR imaging in the second biological window.

Therapeutic Potential of a Small-Molecule STAT3 Inhibitor in a Mouse Model of Colitis.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC). In the current studies, we used the dextran sodium sulfate (DSS) murine model of colitis, which is widely used in preclinical studies, to determine the contribution of STAT3 to IBD. STAT3 has two isoforms: (STAT3 α; which has pro-inflammatory and anti-apoptotic functions, and STAT3ß; which attenuates the effects of STAT3α). In the current study, we determined the contribution of STAT3 to IBD across all tissues by examining DSS-induced colitis in mice that express only STAT3α and in mice treated with TTI-101, a direct small-molecule inhibitor of both isoforms of STAT3. METHODS: We examined mortality, weight loss, rectal bleeding, diarrhea, colon shortening, apoptosis of colonic CD4+ T-cells, and colon infiltration with IL-17-producing cells following 7-day administration of DSS (5%) to transgenic STAT3α knock-in (STAT3ß-deficient; ΔßΔß) mice and wild-type (WT) littermate cage control mice. We also examined the effect of TTI-101 on these endpoints in DSS-induced colitis in WT mice. RESULTS: Each of the clinical manifestations of DSS-induced colitis examined was exacerbated in ΔßΔß transgenic versus cage-control WT mice. Importantly, TTI-101 treatment of DSS-administered WT mice led to complete attenuation of each of the clinical manifestations and also led to increased apoptosis of colonic CD4+ T cells, reduced colon infiltration with IL-17-producing cells, and down-modulation of colon mRNA levels of STAT3-upregulated genes involved in inflammation, apoptosis resistance, and colorectal cancer metastases. CONCLUSIONS: Thus, small-molecule targeting of STAT3 may be of benefit in treating IBD and preventing IBD-associated colorectal cancer.

3D Optical Coherence Thermometry Using Polymeric Nanogels.

In nanothermometry, the use of nanoparticles as thermal probes enables remote and minimally invasive sensing. In the biomedical context, nanothermometry has emerged as a powerful tool where traditional approaches, like infrared thermal sensing and contact thermometers, fall short. Despite the strides of this technology in preclinical settings, nanothermometry is not mature enough to be translated to the bedside. This is due to two major hurdles: the inability to perform 3D thermal imaging and the requirement for tools that are readily available in the clinics. This work simultaneously overcomes both limitations by proposing the technology of optical coherence thermometry (OCTh). This is achieved by combining thermoresponsive polymeric nanogels and optical coherence tomography (OCT)-a 3D imaging technology routinely used in clinical practice. The volume phase transition of the thermoresponsive nanogels causes marked changes in their refractive index, making them temperature-sensitive OCT contrast agents. The ability of OCTh to provide 3D thermal images is demonstrated in tissue phantoms subjected to photothermal processes, and its reliability is corroborated by comparing experimental results with numerical simulations. The results included in this work set credible foundations for the implementation of nanothermometry in the form of OCTh in clinical practice.

Cincuenta años del Departamento de Medicina del Dolor y Paliativa del Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ / Fifty anniversary of the department of pain and palliative medicine at the Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼

Resumen: Introducción: En México, la primera clínica especializada en el alivio del dolor fue fundada en 1972 por el Dr. Ramón De Lille Fuentes en el Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ (INCMNSZ). Material y métodos: Se realizó una búsqueda histórica documental y entrevistas a quienes han colaborado con el Departamento de Medicina del Dolor y Paliativa del INCMNSZ desde su fundación. Resultados: Nuestra visión es ofrecer atención del dolor, cuidados paliativos y apoyo continuo. Para ello, documentamos nuestra historia y los logros del departamento. Conclusiones: A 50 años de su fundación, el Departamento de Medicina del Dolor y Paliativa del INCMNSZ es un foro de desarrollo científico y de formación de capital humano con un enfoque humanista.

Abstract: Introduction: In Mexico, the first clinic specializing in pain relief was founded in 1972 by Dr. Ramón De Lille Fuentes at the Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ (INCMNSZ). Material and methods: A historical documentary search and interviews were carried out with those who have collaborated with the Department of Pain and Palliative Medicine of the INCMNSZ since its foundation. Results: Our vision is to offer pain management, palliative care, and ongoing support. To do this, we document the history and achievements of the department. Conclusions: 50 years after its foundation, the INCMNSZ Department of Pain and Palliative Medicine is a forum for scientific development and human capital training with a humanistic approach.

Relevance of Sugar Transport across the Cell Membrane.

Sugar transport through the plasma membrane is one of the most critical events in the cellular transport of nutrients; for example, glucose has a central role in cellular metabolism and homeostasis. The way sugars enter the cell involves complex systems. Diverse protein systems participate in the membrane traffic of the sugars from the extracellular side to the cytoplasmic side. This diversity makes the phenomenon highly regulated and modulated to satisfy the different needs of each cell line. The beautiful thing about this process is how evolutionary processes have diversified a single function: to move glucose into the cell. The deregulation of these entrance systems causes some diseases. Hence, it is necessary to study them and search for a way to correct the alterations and utilize these mechanisms to promote health. This review will highlight the various mechanisms for importing the valuable sugars needed to create cellular homeostasis and survival in all kinds of cells.

Genetic and Small-Molecule Modulation of Stat3 in a Mouse Model of Crohn's Disease.

Crohn's disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, ß) which are expressed in most cells in a 4:1 ratio (α: ß). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3ß has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in transgenic-mice that express only STAT3α (∆ß/∆ß), as well as in wild-type (WT) mice administered TTI-101 (formerly C188-9), a small molecule STAT3 inhibitor. We determined that clinical manifestations of CD, such as mortality, rectal-bleeding, colonic bleeding, diarrhea, and colon shortening, were exacerbated in ∆ß/∆ß transgenic versus cage-control WT mice, while they were markedly decreased by TTI-101 treatment of WT mice. TTI-101 treatment also increased apoptosis of pathogenic CD4+ T cells and reduced colon levels of IL-17-positive cells. Our results indicate that STAT3 contributes to CD and that targeting of STAT3 with TTI-101 may be a useful approach to treating CD.

Cardiovascular risk in the postnatal life of children born to women with systemic lupus erythematous / Riesgo cardiovascular en la vida posnatal de hijos de mujeres con lupus eritematoso sistémico

Abstract Systemic lupus erythematous (SLE) is an autoimmune disease with clinical manifestations in multiple organs, primarily striking women of reproductive age. Women with SLE can became pregnant such as any other healthy woman and carrier their pregnancy to term due to the improvement of health systems, but their specific inflammatory conditions could affect the microenvironment in which the fetus grows, and influence the development of placenta and the fetal heart. Until now, there is very little evidence of any increased risk of postnatal cardiovascular disease (CVD) in the apparently healthy children from women with SLE, but it is this great variability in the effects of lupus on pregnant products is related to.

Resumen El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que presenta diversas manifestaciones clínicas en múltiples órganos, y afecta principalmente a mujeres en edad reproductiva. Las mujeres con LES se pueden embarazar y llevar a término su embarazo, sin embargo, las condiciones inflamatorias específicas de la madre pueden modificar el microambiente en el que el embrión y el feto se desarrollan y afectar la formación y desarrollo de la placenta y el corazón fetal. Hasta ahora hay muy poca evidencia de que haya un mayor riesgo de enfermedad cardiovascular (ECV) en hijos aparentemente sanos de madres con LES, a pesar de que se sabe que hay un mayor riesgo de alteraciones cognitivas y neuronales, así como de desarrollar enfermedades autoinmunes en esos niños. El objetivo de esta revisión fue realizar una búsqueda bibliografía cruzando palabras clave acerca la enfermedad cardiovascular en hijos sanos de mujeres con LES. La evidencia mostró que la autoinmunidad materna puede favorecer la predisposición para el desarrollo de ECV en sus hijos, por medio de la modificación de señales que alteran el microambiente durante la gestación, lo que puede afectar la respuesta inmunitaria y cambios epigenéticos durante la vida posnatal.

Substance P-Friend or Foe.

Substance P (SP), a neuropeptide and pain transmitter has multiple roles and is involved in various processes in the body [...].

Optical detection of atherosclerosis at molecular level by optical coherence tomography: An in vitro study.

There is an urgent need for contrast agents to detect the first inflammation stage of atherosclerosis by cardiovascular optical coherence tomography (CV-OCT), the imaging technique with the highest spatial resolution and sensitivity of those used during coronary interventions. Gold nanoshells (GNSs) provide the strongest signal by CV-OCT. GNSs are functionalized with the cLABL peptide that binds specifically to the ICAM-1 molecule upregulated in the first stage of atherosclerosis. Dark field microscopy and CV-OCT are used to evaluate the specific adhesion of these functionalized GNSs to activated endothelial cells. This adhesion is investigated under static and dynamic conditions, for shear stresses comparable to those of physiological conditions. An increase in the scattering signal given by the functionalized GNSs attached to activated cells is observed compared to non-activated cells. Thus, cLABL-functionalized GNSs behave as excellent contrast agents for CV-OCT and promise a novel strategy for clinical molecular imaging of atherosclerosis.

Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy.

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.

Cardiovascular risk in the postnatal life of children born to women with systemic lupus erythematous.

Systemic lupus erythematous (SLE) is an autoimmune disease with clinical manifestations in multiple organs, primarily striking women of reproductive age. Women with SLE can became pregnant such as any other healthy woman and carrier their pregnancy to term due to the improvement of health systems, but their specific inflammatory conditions could affect the microenvironment in which the fetus grows, and influence the development of placenta and the fetal heart. Until now, there is very little evidence of any increased risk of postnatal cardiovascular disease (CVD) in the apparently healthy children from women with SLE, but it is this great variability in the effects of lupus on pregnant products is related to.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que presenta diversas manifestaciones clínicas en múltiples órganos, y afecta principalmente a mujeres en edad reproductiva. Las mujeres con LES se pueden embarazar y llevar a término su embarazo, sin embargo, las condiciones inflamatorias específicas de la madre pueden modificar el microambiente en el que el embrión y el feto se desarrollan y afectar la formación y desarrollo de la placenta y el corazón fetal. Hasta ahora hay muy poca evidencia de que haya un mayor riesgo de enfermedad cardiovascular (ECV) en hijos aparentemente sanos de madres con LES, a pesar de que se sabe que hay un mayor riesgo de alteraciones cognitivas y neuronales, así como de desarrollar enfermedades autoinmunes en esos niños. El objetivo de esta revisión fue realizar una búsqueda bibliografía cruzando palabras clave acerca la enfermedad cardiovascular en hijos sanos de mujeres con LES. La evidencia mostró que la autoinmunidad materna puede favorecer la predisposición para el desarrollo de ECV en sus hijos, por medio de la modificación de señales que alteran el microambiente durante la gestación, lo que puede afectar la respuesta inmunitaria y cambios epigenéticos durante la vida posnatal.

Bismuth Selenide Nanostructured Clusters as Optical Coherence Tomography Contrast Agents: Beyond Gold-Based Particles.

Optical coherence tomography (OCT) is an imaging technique currently used in clinical practice to obtain optical biopsies of different biological tissues in a minimally invasive way. Among the contrast agents proposed to increase the efficacy of this imaging method, gold nanoshells (GNSs) are the best performing ones. However, their preparation is generally time-consuming, and they are intrinsically costly to produce. Herein, we propose a more affordable alternative to these contrast agents: Bi2Se3 nanostructured clusters with a desert rose-like morphology prepared via a microwave-assisted method. The structures are prepared in a matter of minutes, feature strong near-infrared extinction properties, and are biocompatible. They also boast a photon-to-heat conversion efficiency of close to 50%, making them good candidates as photothermal therapy agents. In vitro studies evidence the prowess of Bi2Se3 clusters as OCT contrast agents and prove that their performance is comparable to that of GNSs.

Eosin Y-Functionalized Upconverting Nanoparticles: Nanophotosensitizers and Deep Tissue Bioimaging Agents for Simultaneous Therapeutic and Diagnostic Applications.

Functionalized upconverting nanoparticles (UCNPs) are promising theragnostic nanomaterials for simultaneous therapeutic and diagnostic purposes. We present two types of non-toxic eosin Y (EY) nanoconjugates derived from UCNPs as novel nanophotosensitizers (nano-PS) and deep-tissue bioimaging agents employing light at 800 nm. This excitation wavelength ensures minimum cell damage, since the absorption of water is negligible, and increases tissue penetration, enhancing the specificity of the photodynamic treatment (PDT). These UCNPs are uniquely qualified to fulfil three important roles: as nanocarriers, as energy-transfer materials, and as contrast agents. First, the UCNPs enable the transport of EY across the cell membrane of living HeLa cells that would not be possible otherwise. This cellular internalization facilitates the use of such EY-functionalized UCNPs as nano-PS and allows the generation of reactive oxygen species (ROS) under 800 nm light inside the cell. This becomes possible due to the upconversion and energy transfer processes within the UCNPs, circumventing the excitation of EY by green light, which is incompatible with deep tissue applications. Moreover, the functionalized UCNPs present deep tissue NIR-II fluorescence under 808 nm excitation, thus demonstrating their potential as bioimaging agents in the NIR-II biological window.

Erratum: Rodriguez et al. Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis. Cancers 2021, 13, 3871.

One contributor's name was missing in the original version of the authorship of the paper [...].

Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis.

Although cisplatin is very effective as a treatment strategy in triple-negative breast cancer (TNBC), it has unwarranted outcomes owing to recurrence, chemoresistance and neurotoxicity. There is critically important to find new, effective and safe therapeutics for TNBC. We determined if SP-receptor antagonism in combination with cisplatin may serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC. We used a neuronal cell line (PC12) and two TNBC cell lines (Sum 185 and Sum 159) for these studies. We determined that the levels of cells expressing the high-affinity SP-receptor (neurokinin 1 receptor (NK1R)), as determined by flow-cytometry was significantly elevated in response to cisplatin in all three cells. We determined that treatment with aprepitant, an SP-receptor antagonist decreased cisplatin-induced, loss of viability (studied by MTT assay), production of reactive oxygen species (by DCFDA assay) and apoptosis (by flow-cytometry) in PC12 cells while it was increased in the two TNBC cells. Furthermore, we demonstrated that important genes associated with metastases, inflammation, chemoresistance and cell cycle progression are attenuated by SP-receptor antagonism in the TNBC cell line, Sum 185. These studies implicate that SP-receptor antagonism in combination with cisplatin may possibly serve as a novel, more efficacious and safer therapeutic option than existing therapies for TNBC.

Nanoparticles for In Vivo Lifetime Multiplexed Imaging.

Lifetime multiplexed imaging refers to the simultaneous labeling of different structures with fluorescent probes that present identical photoluminescence spectra and distinct fluorescence lifetimes. This technique allows extracting quantitative information from multichannel in vivo fluorescence imaging. In vivo lifetime multiplexed imaging requires fluorophores with excitation and emission bands in the near-infrared (NIR) and tunable fluorescence lifetimes, plus an imaging system capable of time-resolved image acquisition and analysis.

Substance P Antagonism Prevents Chemotherapy-Induced Cardiotoxicity.

Background: Doxorubicin (DOX), used in chemotherapeutic regimens in many cancers, has been known to induce, cardiotoxicity and life-threatening heart failure or acute coronary syndromes in some patients. We determined the role of Substance P (SP), a neuropeptide and its high affinity receptor, NK-1R in chemotherapy associated cardiotoxicity in mice. We determined if NK-1R antagonism will prevent DOX-induced cardiotoxicity in vivo. Methods: C57BL/6 mice (6- week old male) were injected intraperitoneally with DOX (5 mg per kilogram of body weight once a week for 5 weeks) with or without treatment with aprepitant (a NK-1R antagonist, Emend, Merck & Co., Kenilworth, NJ, USA). Five different dosages of aprepitant were administered in the drinking water five days before the first injection of DOX and then continued until the end of the experiment. Each of these 5 doses are as follows; Dose 1 = 0.9 µg/mL, Dose 2 = 1.8 µg/mL, Dose 3 = 3.6 µg/mL, Dose 4 = 7.2 µg/mL, Dose 5 = 14.4 µg/mL. Controls consisted of mice injected with PBS (instead of DOX) with or without aprepitant treatment. The experiment was terminated 5 weeks post-DOX administration and various cardiac functional parameters were determined. Following euthanization, we measured heart weight to body weight ratios and the following in the hearts, of mice treated with and without DOX and aprepitant; (a) levels of SP and NK1R, (b) cardiomyocyte diameter (to determine evidence of cardiomyocyte hypertrophy), (c) Annexin V levels (to determine evidence of cardiac apoptosis), and (d) ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) (to determine evidence of oxidative stress). Results: We demonstrated that the levels of SP and NK1R were significantly increased respectively by 2.07 fold and 1.86 fold in the hearts of mice treated with versus without DOX. We determined that DOX-induced cardiac dysfunction was significantly attenuated by treatment with aprepitant. Cardiac functional parameters such as fractional shortening (FS), ejection fraction (EF) and stroke volume (SV) were respectively decreased by 27.6%, 21.02% and 21.20% compared to the vehicle treated group (All, p < 0.05, ANOVA). Importantly, compared to treatment with DOX alone, treatment with lower doses of aprepitant in DOX treated mice significantly reduced the effects of DOX on FS, EF and SV to values not significantly different from sham (vehicle treated) mice (All, p < 0.05, ANOVA). The levels of, apoptosis marker (Annexin V), oxidative stress (ratio of GSH with GSSG) and cardiomyocyte hypertrophy were respectively increased by 47.61%, 91.43% and 47.54% in the hearts of mice treated with versus without DOX. Compared to the DOX alone group, treatment with DOX and Dose 1, 2 and 3 of aprepitant significantly decreased the levels of each of these parameters (All p < 0.05, ANOVA). Conclusions: Our studies indicate that the SP/NK1-R system is a key mediator that induces, DOX-induced, cardiac dysfunction, cardiac apoptosis, cardiac oxidative stress and cardiomyocyte hypertrophy. These studies implicate that NK-1R antagonists may serve as a novel therapeutic tool for prevention of chemotherapy induced cardiotoxicity in cancer.