Beyond the beat: A pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health.

Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes.

Single-cell RNA Sequencing (scRNA-seq): Advances and Challenges for Cardiovascular Diseases (CVDs).

Implementing Single-cell RNA sequencing (scRNA-seq) has significantly enhanced our comprehension of cardiovascular diseases (CVDs), providing new opportunities to strengthen the prevention of CVDs progression. Cardiovascular diseases continue to be the primary cause of death worldwide. Improving treatment strategies and patient risk assessment requires a deeper understanding of the fundamental mechanisms underlying these disorders.

Modulation of the Immune System Mechanisms using Probiotic Bacteria in Allergic Diseases: Focus on Allergic Retinitis and Food Allergies.

Allergic illnesses occur when an organism's immune system is excessively responsive to certain antigens, such as those that are presented in the environment. Some people suffer from a wide range of immune system-related illnesses including allergic rhinitis, asthma, food allergies, hay fever, and even anaphylaxis. Immunotherapy and medications are frequently used to treat allergic disorders.

New Approaches Targeting the Renin-Angiotensin System: Inhibition of Brain Aminopeptidase A, ACE2 Ubiquitination, and Angiotensinogen.

Despite the availability of various therapeutic classes of antihypertensive drugs, hypertension remains poorly controlled, in part because of poor adherence. Hence, there is a need for the development of antihypertensive drugs acting on new targets to improve control of blood pressure. This review discusses novel insights (including the data of recent clinical trials) with regard to interference with the renin-angiotensin system, focusing on the enzymes aminopeptidase A and angiotensin-converting enzyme 2 (ACE2) in the brain, as well as the substrate of renin- angiotensinogen-in the liver.

Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.

Aims: Angiotensin-converting enzyme 2 (ACE2) is a critical component of the compensatory renin-angiotensin system that is down-regulated during the development of hypertension, possibly via ubiquitination. However, little is known about the mechanisms involved in ACE2 ubiquitination in neurogenic hypertension. This study aimed at identifying ACE2 ubiquitination partners, establishing causal relationships and clinical relevance, and testing a gene therapy strategy to mitigate ACE2 ubiquitination in neurogenic hypertension.

Real-Time Visualization of Cytosolic and Mitochondrial ATP Dynamics in Response to Metabolic Stress in Cultured Cells.

Adenosine 5' triphosphate (ATP) is the energy currency of life, which is produced in mitochondria (~90%) and cytosol (less than 10%). Real-time effects of metabolic changes on cellular ATP dynamics remain indeterminate. Here we report the design and validation of a genetically encoded fluorescent ATP indicator that allows for real-time, simultaneous visualization of cytosolic and mitochondrial ATP in cultured cells.

Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a "2-Hit" Murine Model.

Background Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a "2-hit" murine model.

Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia.

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model.

Hydrogen Sulfide Modulates Endothelial-Mesenchymal Transition in Heart Failure.

Background: Hydrogen sulfide is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure. Cystathionine γ-lyase (CSE), 1 of 3 hydrogen-sulfide-producing enzyme, is predominantly localized in the vascular endothelium. The interaction between the endothelial CSE-hydrogen sulfide axis and endothelial-mesenchymal transition, an important pathological process contributing to the formation of fibrosis, has yet to be investigated.

Soluble urokinase plasminogen activator receptor: from biomarker to active participant in atherosclerosis and cardiovascular disease.

Atherosclerosis contributes to the majority of deaths related to cardiovascular disease (CVD). Recently, the nonspecific inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) has shown prognostic value in patients with CVD; however, it remains unclear whether suPAR participates in the disease process. In this issue of the JCI, Hindy and colleagues report on their evaluation of a multi-ethnic cohort of over 5,000 participants without known CVD.

Nicotine and novel tobacco products drive adverse cardiac remodeling and dysfunction in preclinical studies.

Background: The heart undergoes structural and functional changes in response to injury and hemodynamic stress known as cardiac remodeling. Cardiac remodeling often decompensates causing dysfunction and heart failure (HF). Cardiac remodeling and dysfunction are significantly associated with cigarette smoking.

A combination of novel NSC small molecule inhibitor along with doxorubicin inhibits proliferation of triple-negative breast cancer through metabolic reprogramming.

Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to the absence of well-defined molecular targets and the highly invasive and proliferative nature of TNBC cells. Current treatments against TNBC have shown little promise due to high recurrence rate in patients. Consequently, there is a pressing need for novel and efficacious therapies against TNBC.

Ovarian hormones do not mediate protection against pulmonary hypertension and right ventricular remodeling in female mice exposed to chronic, inhaled nicotine.

Electronic cigarette use has increased globally prompting calls for improved understanding of nicotine's cardiovascular health effects. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension and right ventricular (RV) remodeling in male mice, but not female mice, suggesting sex differences in nicotine-related pathology. Clinically, biological females develop pulmonary hypertension more often but have less severe disease than biological males, likely because of the cardiopulmonary protective effects of estrogen.

Difelikefalin, a peripherally restricted KOR (kappa opioid receptor) agonist, produces diuresis through a central KOR pathway.

Difelikefalin is a peripherally restricted kappa opioid receptor (KOR) agonist that was recently approved by the FDA to treat pruritis in dialysis patients. Here, we investigated the cardiovascular and renal responses to difelikefalin, and using the KOR antagonist norbinaltorphimine (norBNI), examined whether any difelikefalin-induced changes in the renal excretion of water and/or electrolytes were mediated through a central or peripheral KOR pathway. The effects of norBNI pretreatment on nalfurafine, a KOR agonist that crosses the blood-brain barrier, were also examined.

Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine.

Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod.

Serum Metabolomics Reveals Distinct Profiles during Ischemia and Reperfusion in a Porcine Model of Myocardial Ischemia-Reperfusion.

Acute myocardial infarction (MI) is one of the leading causes of death worldwide. Early identification of ischemia and establishing reperfusion remain cornerstones in the treatment of MI, as mortality and morbidity can be significantly reduced by establishing reperfusion to the affected areas. The aim of the current study was to investigate the metabolomic changes in the serum in a swine model of MI induced by ischemia and reperfusion (I/R) injury, and to identify circulating metabolomic biomarkers for myocardial injury at different phases.

Genetically Encoded ATP Biosensors for Direct Monitoring of Cellular ATP Dynamics.

Adenosine 5'-triphosphate, or ATP, is the primary molecule for storing and transferring energy in cells. ATP is mainly produced via oxidative phosphorylation in mitochondria, and to a lesser extent, via glycolysis in the cytosol. In general, cytosolic glycolysis is the primary ATP producer in proliferative cells or cells subjected to hypoxia.

Mitochondrial HS Regulates BCAA Catabolism in Heart Failure.

Background: Hydrogen sulfide (HS) exerts mitochondria-specific actions that include the preservation of oxidative phosphorylation, biogenesis, and ATP synthesis, while inhibiting cell death. 3-MST (3-mercaptopyruvate sulfurtransferase) is a mitochondrial HS-producing enzyme whose functions in the cardiovascular disease are not fully understood. In the current study, we investigated the effects of global 3-MST deficiency in the setting of pressure overload-induced heart failure.

Alpha7 nicotinic acetylcholine receptor mediates chronic nicotine inhalation-induced cardiopulmonary dysfunction.

Cigarette smoking remains the leading modifiable risk factor for cardiopulmonary diseases; however, the effects of nicotine alone on cardiopulmonary function remain largely unknown. Previously, we have shown that chronic nicotine vapor inhalation in mice leads to the development of pulmonary hypertension (PH) with right ventricular (RV) remodeling. The present study aims to further examine the cardiopulmonary effects of nicotine and the role of the α7 nicotinic acetylcholine receptor (α7-nAChR), which is widely expressed in the cardiovascular system.

Nischarin Deletion Reduces Oxidative Metabolism and Overall ATP: A Study Using a Novel Knockout Mouse Model.

Nischarin (Nisch) is a cytosolic scaffolding protein that harbors tumor-suppressor-like characteristics. Previous studies have shown that Nisch functions as a scaffolding protein and regulates multiple biological activities. In the current study, we prepared a complete Nisch knockout model, for the first time, by deletion of exons 5 and 6.