Dysregulation of HO-1-SIRT1 Axis is Associated with AngII-Induced Adipocyte Dysfunction.

Angiotensin II (AngII), a component of the Renin-Angiotensin-Aldosterone System (RAAS), has been implicated in the dysregulation of adipose tissue function. Inhibition of AngII has been shown to improve adipose tissue function in mice with metabolic syndrome. It is well established that the Heme Oxygenase-1 (HO-1), an antioxidant improves oxidative stress and phenotypic change in adipocytes.

Enhancing Heart Failure Diagnosis Accuracy and Distinguishing It From Other Pulmonary Conditions: A Retrospective Case Series Study Leveraging the HeartLogic Parameters.

Introduction Heart failure (HF) poses a substantial and escalating medical and economic challenge, marked by significant morbidity and mortality. It stands as the primary cause of hospital admissions among the elderly, contributing significantly to healthcare expenditures in developed nations. Evaluating cardiac and pulmonary function remains challenging, necessitating careful interpretation to mitigate misdiagnosis and inappropriate treatment.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis.

COVID-19-Associated Sepsis: Potential Role of Phytochemicals as Functional Foods and Nutraceuticals.

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19.

pNaKtide Inhibits Na/K-ATPase Signaling and Attenuates Obesity.

Obesity is a growing public health crisis across the world and has been recognized as an underlying risk factor for metabolic syndrome. Growing evidence demonstrates the critical role of oxidative stress in the pathophysiological mechanisms of obesity and related metabolic dysfunction. As we have established previously that Na/K-ATPase can amplify oxidative stress signaling, we aimed to explore the effect of inhibition of this pathway on obesity phenotype using the peptide antagonist, pNaKtide.

Erratum: Role of adipocyte Na,K-ATPase oxidant amplification loop in cognitive decline and neurodegeneration.

[This corrects the article DOI: 10.1016/j.isci.

Adipocyte Na, K-ATPase Signaling Attenuates Experimental Uremic Cardiomyopathy.

Oxidative stress has been shown to cause an alteration of intracellular signaling in adipocytes that may lead to various comorbidities of obesity and cardiovascular complications. Evidence suggests that dysregulation of Na, K-ATPase signaling can contribute to systemic inflammation and redox signaling that leads to various metabolic disturbances. Hence the present study aims to explore the specific role of adipocyte Na, K-ATPase signaling in the amelioration of pathophysiological alterations of experimental uremic cardiomyopathy.

Transitioning to Unfractionated Heparin in Treatment of Non-ST-Segment Elevation Myocardial Infarction Patients on Direct Oral Anti-Xa Inhibitors.

The heparin anti-Xa assay is affected by the use of direct oral anticoagulants (DOACs) and is utilized in the management of intravenous unfractionated heparin. Patients with non-ST-segment myocardial infarction (NSTEMI) receive intravenous unfractionated heparin with prior administration of DOACs poses challenges given these laboratory abnormalities. On this background, we evaluate if an elevated heparin anti-Xa assay may lead to the decision to delay heparin in the management of NSTEMI patients and the outcome of in-hospital mortality.

Inhibition of Na/K-ATPase signaling Attenuates Steatohepatitis and Atherosclerosis in Mice Fed a Western Diet.

We have previously reported that the α1 subunit of sodium-potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that the blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose.

Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL.

Introduction: Adipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes shows pro-inflammatory phenotypes accompanied by oxidative stress and abnormal secretion. Nevertheless, molecular mechanisms of how adipocytes are stimulated to secrete exosomes under those conditions remain poorly understood.

Prevalence of Substance Abuse Among Trauma Patients in Rural West Virginia.

Background:  Substance abuse poses considerable clinical, economic, and social challenges. West Virginia is hailed as the epicenter of the substance abuse in the United States, the prevalence and pattern of different trauma mechanisms in a rural context or in patients with different forms of substance abuse remain unclear.

Objective:  We performed the following analysis to understand the prevalence of substance abuse in patients with different trauma mechanisms in the rural setting with high substance abuse in the West Virginia.

Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs.

COVID-19 is renowned as a multi-organ disease having subacute and long-term effects with a broad spectrum of clinical manifestations. The evolving scientific and clinical evidence demonstrates that the frequency of cognitive impairment after COVID-19 is high and it is crucial to explore more clinical research and implement proper diagnostic and treatment strategies. Several central nervous system complications have been reported as comorbidities of COVID-19.

Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.

Na/K-ATPase (NKA), besides its ion transporter function, is a signal transducer by regulating Src family kinases (SFK). The signaling NKA contributes to oxidized LDL-induced macrophage foam cell formation and interacts with TLR4. However, its role in lipopolysaccharides (LPS)-induced signaling and glycolytic switch in macrophages remains unclear.

Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.

Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity.

Gene module regulation in dilated cardiomyopathy and the role of Na/K-ATPase.

Dilated cardiomyopathy (DCM) is a major cause of cardiac death and heart transplantation. It has been known that black people have a higher incidence of heart failure and related diseases compared to white people. To identify the relationship between gene expression and cardiac function in DCM patients, we performed pathway analysis and weighted gene co-expression network analysis (WGCNA) using RNA-sequencing data (GSE141910) from the NCBI Gene Expression Omnibus (GEO) database and identified several gene modules that were significantly associated with the left ventricle ejection fraction (LVEF) and DCM phenotype.

Tumor-Suppressor Role of the α1-Na/K-ATPase Signalosome in NASH Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, with an estimate of 0.84 million cases every year. In Western countries, because of the obesity epidemic, non-alcoholic steatohepatitis (NASH) has become the major cause of HCC.

Optimization of Prescription Drug Monitoring Program to Overcome Opioid Epidemic in West Virginia.

The development of the Prescription Drug Monitoring Program (PDMP) led to an innovation in the healthcare organization system (HCOs). The PDMP system has been utilized in different states at various organizational levels in an effort to achieve improved health outcomes, reduce the number of prescription drug overdoses, and lighten the economic burden that follows. However, during the implementation of PDMP, there were several barriers and limitations that were discovered.

Gut microbiome and diet in populations with obesity: Role of the Na+/K+-ATPase transporter signaling in severe COVID-19.

Objective: The triad of obesity, a high-protein diet from animal sources, and disturbed gut microbiota have been linked to poor clinical outcomes in patients with COVID-19. In this report, the effect of oxidative stress resulting from the Na /K -ATPase transporter signaling cascade is explored as a driver of this poor clinical outcome.

Methods: Protein-protein interactions with the SARS-CoV-2 proteome were identified from the interactome data for Na /K -transporting ATPase subunit α-1 (ATP1A1), epidermal growth factor receptor, and ERB-B2 receptor tyrosine kinase 2, using the curated data from the BioGRID Database of Protein Interactions.

Role of adipocyte Na,K-ATPase oxidant amplification loop in cognitive decline and neurodegeneration.

Recent studies suggest that a western diet may contribute to clinical neurodegeneration and dementia. Adipocyte-specific expression of the Na,K-ATPase signaling antagonist, NaKtide, ameliorates the pathophysiological consequences of murine experimental obesity and renal failure. In this study, we found that a western diet produced systemic oxidant stress along with evidence of activation of Na,K-ATPase signaling within both murine brain and peripheral tissues.

A Review of miRNAs as Biomarkers and Effect of Dietary Modulation in Obesity Associated Cognitive Decline and Neurodegenerative Disorders.

There has been a progressive increase in the prevalence of obesity and its comorbidities such as type 2 diabetes and cardiovascular diseases worldwide. Recent studies have suggested that the crosstalk between adipose tissue and central nervous system (CNS), through cellular mediators and signaling pathways, may causally link obesity with cognitive decline and give rise to neurodegenerative disorders. Several mechanisms have been proposed in obesity, including inflammation, oxidative stress, insulin resistance, altered lipid and cholesterol homeostasis, which may result in neuroinflammation, altered brain insulin signaling, amyloid-beta (Aβ) deposition and neuronal cell death.

The Na/K-ATPase Signaling and SGLT2 Inhibitor-Mediated Cardiorenal Protection: A Crossed Road?

In different large-scale clinic outcome trials, sodium (Na)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na gradient to drive other Na-dependent transporters, the possible role of the sodium-potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored.