Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes.

Introduction: Disulfiram (DSF) reduces insulin resistance and weight gain in obese mice. However, the effect on adipose tissue is unexplored due to their high instability under physiological conditions, limiting clinical applications. Thus, it is meaningful to develop a DSF carrier for sustained release to adipose tissue.

MICU3 Regulates Mitochondrial Calcium and Cardiac Hypertrophy.

Background: Calcium (Ca) uptake by mitochondria occurs via the mitochondrial Ca uniporter. Mitochondrial Ca uniporter exists as a complex, regulated by 3 MICU (mitochondrial Ca uptake) proteins localized in the intermembrane space: MICU1, MICU2, and MICU3. Although MICU3 is present in the heart, its role is largely unknown.

Mechanisms of reduced myocardial energetics of the dystrophic heart.

Heart disease is a leading cause of death in patients with Duchenne muscular dystrophy (DMD), characterized by the progressive replacement of contractile tissue with scar tissue. Effective therapies for dystrophic cardiomyopathy will require addressing the disease before the onset of fibrosis, however, the mechanisms of the early disease are poorly understood. To understand the pathophysiology of DMD, we perform a detailed functional assessment of cardiac function of the mdx mouse, a model of DMD.

Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term.

Transport of Ca into mitochondria is thought to stimulate the production of ATP, a critical process in the heart's fight or flight response, but excess Ca can trigger cell death. The mitochondrial Ca uniporter complex is the primary route of Ca transport into mitochondria, in which the channel-forming protein MCU and the regulatory protein EMRE are essential for activity. In previous studies, chronic Mcu or Emre deletion differed from acute cardiac Mcu deletion in response to adrenergic stimulation and ischemia/reperfusion (I/R) injury, despite equivalent inactivation of rapid mitochondrial Ca uptake.

Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vessel remodeling; however, its severity and impact on survival depend on right ventricular (RV) failure. Resveratrol (RES), a polyphenol found in red wine, exhibits cardioprotective effects on RV dysfunction in PAH. However, most literature has focused on RES protective effect on lung vasculature; recent finding indicates that RES has a cardioprotective effect independent of pulmonary arterial pressure on RV dysfunction, although the underlying mechanism in RV has not been determined.

A single session of physical activity restores the mitochondrial organization disrupted by obesity in skeletal muscle fibers.

Background: Several studies have proved that physical activity (PA) regulates energetic metabolism associated with mitochondrial dynamics through AMPK activation in healthy subjects. Obesity, a condition that induces oxidative stress, mitochondrial dysfunction, and low AMPK activity leads to mitochondrial fragmentation. However, few studies describe the effect of PA on mitochondrial dynamics regulation in obesity.

Amorphous SiO2 nanoparticles promote cardiac dysfunction via the opening of the mitochondrial permeability transition pore in rat heart and human cardiomyocytes.

Background: Silica nanoparticles (nanoSiO) are promising systems that can deliver biologically active compounds to tissues such as the heart in a controllable manner. However, cardiac toxicity induced by nanoSiO has been recently related to abnormal calcium handling and energetic failure in cardiomyocytes. Moreover, the precise mechanisms underlying this energetic debacle remain unclear.

Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature.

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated.

Changes in the Stoichiometry of Uniplex Decrease Mitochondrial Calcium Overload and Contribute to Tolerance of Cardiac Ischemia/Reperfusion Injury in Hypothyroidism.

Thyroid hormone status in hypothyroidism (HT) downregulates key elements in Ca handling within the heart, reducing contractility, impairing the basal energetic balance, and increasing the risk of cardiovascular disease. Mitochondrial Ca transport is reduced in HT, and tolerance to reperfusion damage has been documented, but the precise mechanism is not well understood. Therefore, we aimed to determine the stoichiometry and activity of the mitochondrial Ca uniporter or uniplex in an HT model and the relevance to the opening of the mitochondrial permeability transition pores (mPTP) during ischemia/reperfusion (I/R) injury.

Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis.

Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes.

Microbial Competition of Rhodotorula mucilaginosa UANL-001L and E. coli increase biosynthesis of Non-Toxic Exopolysaccharide with Applications as a Wide-Spectrum Antimicrobial.

Bacterial species are able to colonize and establish communities in biotic and abiotic surfaces. Moreover, within the past five decades, incidence of bacterial strains resistant to currently used antibiotics has increased dramatically. This has led to diverse health issues and economical losses for different industries.

Small Interfering RNA Targeting Mitochondrial Calcium Uniporter Improves Cardiomyocyte Cell Viability in Hypoxia/Reoxygenation Injury by Reducing Calcium Overload.

Intracellular Ca mishandling is an underlying mechanism in hypoxia/reoxygenation (H/R) injury that results in mitochondrial dysfunction and cardiomyocytes death. These events are mediated by mitochondrial Ca (Ca) overload that is facilitated by the mitochondrial calcium uniporter (MCU) channel. Along this line, we evaluated the effect of siRNA-targeting MCU in cardiomyocytes subjected to H/R injury.

Therapeutic silencing of HPV 16 E7 by systemic administration of siRNA-neutral DOPC nanoliposome in a murine cervical cancer model with obesity.

Purpose: To evaluate the effectiveness of a neutral DOPC nanoliposome system for the delivery of siRNA to tumor cells in an obese murine cervical cancer model.

Methods: In vitro silencing of E6-E7 mRNA and E7 protein using siRNAE6 or siRNAE7 was analyzed in TC-1 cells by RT-PCR and Western blot. Silencing and antitumor capacities of siRNAE7-DOPC-nanoparticles (NP) were tested in vivo in both normal and obese mice using qPCR.