Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischemic injury involves direct activation of mitochondrial sirtuin 3.

Aims: Although current clinical therapies following myocardial infarction have improved patient outcomes, morbidity, and mortality rates secondary to ischemic and ischemia reperfusion (IR) injury remains high. Maintaining mitochondrial quality is essential to limit myocardial damage following cardiac ischemia and IR injury. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in regulating mitochondrial function and cardiac energy metabolism.

The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischaemic heart failure.

Aims: Cardiac energy metabolism is perturbed in ischaemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown.

Mitochondrial fatty acid oxidation is the major source of cardiac adenosine triphosphate production in heart failure with preserved ejection fraction.

Aims: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remains unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF.

Stimulating cardiac glucose oxidation lessens the severity of heart failure in aged female mice.

Heart failure is a prevalent disease worldwide. While it is well accepted that heart failure involves changes in myocardial energetics, what alterations that occur in fatty acid oxidation and glucose oxidation in the failing heart remains controversial. The goal of the study are to define the energy metabolic profile in heart failure induced by obesity and hypertension in aged female mice, and to attempt to lessen the severity of heart failure by stimulating myocardial glucose oxidation.

Amlodipine rescues advanced iron overload cardiomyopathy in hemojuvelin knockout murine model: Clinical implications.

Background: Iron overload cardiomyopathy (IOC) is a major co-morbidity of genetic hemochromatosis and secondary iron overload with limited therapeutic options. We aim to investigate mechanisms of rescue action of amlodipine in the murine model of iron overload, characterize changes in human cardiac tissue due to IOC, and compare them to the changes in the animal model of IOC.

Methods And Results: As an animal model, we used male hemojuvelin knockout (HJVKO) mice, which lacked hemojuvelin (a co-receptor protein for hepcidin expression).

Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway.

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect.

Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans.

Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non-invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non-failing control (NFC, n=46) explanted human hearts.

Natural History of a Mouse Model Overexpressing the Dp71 Dystrophin Isoform.

Dystrophin is a 427 kDa protein that stabilizes muscle cell membranes through interactions with the cytoskeleton and various membrane-associated proteins. Loss of dystrophin as in Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle weakness and cardiac dysfunction. Multiple promoters along the dystrophin gene () give rise to a number of shorter isoforms.

Barth syndrome-related cardiomyopathy is associated with a reduction in myocardial glucose oxidation.

Heart failure presents as the leading cause of infant mortality in individuals with Barth syndrome (BTHS), a rare genetic disorder due to mutations in the tafazzin () gene affecting mitochondrial structure and function. Investigations into the perturbed bioenergetics in the BTHS heart remain limited. Hence, our objective was to identify the potential alterations in myocardial energy metabolism and molecular underpinnings that may contribute to the early cardiomyopathy and heart failure development in BTHS.

Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels.

[Figure: see text].

Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis.

Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown.

Modulation of bone formation and resorption using a novel zoledronic acid loaded gelatin nanoparticles integrated porous titanium scaffold: an in vitro and in vivo study.

Osteoporotic bone defects are a major challenge in clinics for bone regeneration. With the condition of osteoporosis, excessive bone absorption and impaired osteogenesis result in unexpectedly long healing procedures for defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffold was designed, to be integrated with anti-catabolic drug zoledronic acid nanoparticles (ZOL loaded gelatin NPs), which was able to achieve a local sustained release of ZOL as expected.

Analysis and Classification for Single-Trial EEG Induced by Sequential Finger Movements.

In recent years, motor imagery-based BCIs (MI-BCIs) controlled various external devices successfully, which have great potential in neurological rehabilitation. In this paper, we designed a paradigm of sequential finger movements and utilized spatial filters for feature extraction to classify single-trial electroencephalography (EEG) induced by finger movements of left and right hand. Ten healthy subjects participated the experiment.

Effects of Gastrin-releasing Peptide on Hippocampal Neural Networks in Vascular Dementia Rats.

Gastrin-releasing peptide (GRP) has been confirmed to exhibit a variety of physiological functions in the brain and play a role in many neurological diseases. Our previous research found that GRP could restore the impaired synaptic plasticity and the spatial learning and memory impairments induced by vascular dementia (VD). However, the specific mechanisms of GRP affecting hippocampus, especially the effects on the neuronal oscillations were still poorly understood.

Low-Frequency Pulsed Magnetic Field Improves Depression-Like Behaviors and Cognitive Impairments in Depressive Rats Mainly via Modulating Synaptic Function.

Transcranial magnetic stimulation (TMS) has shown great promise as a medical treatment of depression. The effectiveness of TMS treatment at high frequency has been well investigated; however, low-frequency TMS in depression treatment has rarely been investigated in depression-induced cognitive deficits. Herein, this study was carried out to assess the possible modulatory role of low-frequency pulsed magnetic field (LFPMF) on reversing cognitive impairment in a model of depression induced by chronic unpredictable stress (CUS).

Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs.

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival.

PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.

Background Cancer therapies inhibiting PI 3Kα (phosphoinositide 3-kinase-α)-dependent growth factor signaling, including trastuzumab inhibition of HER 2 (Human Epidermal Growth Factor Receptor 2), can cause adverse effects on the heart. Direct inhibition of PI 3Kα is now in clinical trials, but the effects of PI 3Kα pathway inhibition on heart atrophy, remodeling, and function in the context of cancer therapy are not well understood. Method and Results Pharmacological PI 3Kα inhibition and heart-specific genetic deletion of p110α, the catalytic subunit of PI 3Kα, was characterized in conjunction with anthracycline (doxorubicin) treatment in female murine models.

PI3Kα-regulated gelsolin activity is a critical determinant of cardiac cytoskeletal remodeling and heart disease.

Biomechanical stress and cytoskeletal remodeling are key determinants of cellular homeostasis and tissue responses to mechanical stimuli and injury. Here we document the increased activity of gelsolin, an actin filament severing and capping protein, in failing human hearts. Deletion of gelsolin prevents biomechanical stress-induced adverse cytoskeletal remodeling and heart failure in mice.

Modulation of Low-Frequency Pulsed Magnetic Field on Hippocampal Neural Oscillation in Depression Rats.

Transcranial magnetic stimulation (TMS), as a non-invasive brain stimulation technique, has been approved for some medication-resistant depression by the United States Food and Drug Administration. However, the majority of these studies have focused on the effects of high-frequency TMS, and little is known about low-frequency TMS in depression treatment. Furthermore, the potential electroneurophysiology mechanisms of TMS on the improvement of and function of the brain remain poorly understood.

Evaluation of an artificial vertebral body fabricated by a tantalum-coated porous titanium scaffold for lumbar vertebral defect repair in rabbits.

Tantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated the healing and fusion efficacy of this scaffold in lumbar vertebral defects after corpectomy in rabbits. The results showed that BMSCs on the surface of the Ta-coated Ti scaffolds proliferated better than BMSCs on Ti scaffolds.

Effects of Moisture Content and Loading Profile on Changing Properties of Bone Micro-Biomechanical Characteristics.

BACKGROUND Our study explored the influences of hydration conditions and loading methods on the mechanical properties of cortical bones and cancellous bones. MATERIAL AND METHODS Elastic modulus and hardness of human cortical bones and cancellous bones that contained different moisture levels (20%, 30%, 40%, 50%, and 60%) were measured with nanoindentation with different peak loads and loading rates. Cortical bones with 20% and 60% moisture were tested with 30 nm, 40 nm, and 50 nm peak loads at 6 nm/s, 8 nm/s, and 10 nm/s loading rates, respectively.

Bombesin attenuated ischemia-induced spatial cognitive and synaptic plasticity impairment associated with oxidative damage.

The dysfunction of spatial cognition is a character to various neurological disorders and therapeutic strategy. However, it is limited to known risk factors clinically so far. Gastrin releasing peptide (GRP) signaling is a neuropeptide system mediating emotional memory events.

[Progress in the application of neural oscillations cross-frequency coupling in cognitive function research].

Neural oscillations cross-frequency coupling (CFC) refers to the effect of the cross modulation between the electrophysiological oscillation rhythm in different ensembles of neurons. The CFC can reflect the mechanism of information transfer and exchange of local field potentials, electroencephalograph (EEG) and other neural electrophysiological activities at different spatial and temporal scales and plays an important role in the study of cognitive function. This paper introduces the basic phenomenon and classifications of neural oscillation CFC briefly, and reviews the typical applications in the study of the animal cognition model and human cognitive function in recent years, respectively.