Fine particulate matter (PM)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony.

Results of human and animal studies independently suggest that either ambient fine particulate matter (PM) air pollution exposure or a disturbed circadian rhythm (circadian dyssynchrony) are important contributing factors to the rapidly evolving type-2-diabetes (T2D) epidemic. The objective of this study is to investigate whether circadian dyssynchrony increases the susceptibility to PM and how PM affects metabolic health in circadian dyssynchrony. We examined systemic and organ-specific changes in glucose homeostasis and insulin sensitivity in mice maintained on a regular (12/12 h light/dark) or disrupted (18/6 h light/dark, light-induced circadian dyssynchrony, LICD) light cycle exposed to air or concentrated PM (CAP, 6 h/day, 30 days).

A New Look at Barriers to Clinical Care Among Appalachian Residents Living With Diabetes.

In the United States, diabetes is the seventh leading cause of death and continues to rise in prevalence, with type 2 diabetes accounting for 90-95% of all cases. Rates of diabetes in Kentucky, and, in particular, the Appalachian region, are among the highest in the nation and are increasing faster than the national average. Despite this disproportionate burden, barriers to clinical appointment attendance have not been fully explored in this population.

Root Cause for Metabolic Syndrome and Type 2 Diabetes: Can Lifestyle and Nutrition Be the Answer for Remission.

Obesity and its association with metabolic syndrome are implicated in many disease states. Research has focused on the role of diet and lifestyle modifications in the evolution of prediabetes to diabetes seeking ways to intervene and improve outcomes. Proven nutritional include leaner proteins, an abundance of vegetables, extra-virgin olive oil, and controlled portioning of carbs and starches.

Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes.

Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when challenged with a high fat diet. Here, we studied the transcriptional response of the adipose tissue of these mice to acute high fat diet exposure.

Tris(1,3-dichloro-2-propyl) phosphate is a metabolism-disrupting chemical in male mice.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphate flame retardant. The primary TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), is detectable in the urine of over 90 % of Americans. Epidemiological studies show sex-specific associations between urinary BDCPP levels and metabolic syndrome, which is an established risk factor for type 2 diabetes, heart disease, and stroke.

Heart rate recovery as an assessment of cardiorespiratory fitness in young adults.

Background: Cardiorespiratory fitness, typically measured as peak oxygen uptake (VO) during maximal graded exercise testing (GXT), is a predictor of morbidity, mortality, and cardiovascular disease. However, measuring VO is costly and inconvenient and thus not widely used in clinical settings. Alternatively, postexercise heart rate recovery (HRRec), which is an index of vagal reactivation, is a valuable assessment of VO in older adults and athletes.

Exercise-induced specialized proresolving mediators stimulate AMPK phosphorylation to promote mitochondrial respiration in macrophages.

Objective: Physical activity has been shown to reduce the risk of CVD mortality in large-cohort longitudinal studies; however, the mechanisms underpinning the beneficial effects of exercise remain incompletely understood. Emerging data suggest that the risk reducing effect of exercise extends beyond changes in traditional CVD risk factors alone and involves alterations in immunity and reductions in inflammatory mediator production. Our study aimed to determine whether exercise-enhanced production of proresolving lipid mediators contribute to alterations in macrophage intermediary metabolism, which may contribute to the anti-inflammatory effects of exercise.

The Detection of Periodic Reemergence Events of SARS-CoV-2 Delta Strain in Communities Dominated by Omicron.

Despite entering an endemic phase, SARS-CoV-2 remains a significant burden to public health across the global community. Wastewater sampling has consistently proven utility to understanding SARS-CoV-2 prevalence trends and genetic variation as it represents a less biased assessment of the corresponding communities. Here, we report that ongoing monitoring of SARS-CoV-2 genetic variation in samples obtained from the wastewatersheds of the city of Louisville in Jefferson county Kentucky has revealed the periodic reemergence of the Delta strain in the presence of the presumed dominant Omicron strain.

E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice.

E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation.

Transient gene therapy using cell cycle factors reverses renin-angiotensin-aldosterone system activation in heart failure rat model.

The loss of cardiomyocytes after myocardial infarction (MI) leads to heart failure. Recently, we demonstrated that transient overexpression of 4 cell cycle factors (4F), using a polycistronic non-integrating lentivirus (TNNT2-4F-NIL) resulted in significant improvement in cardiac function in a rat model of MI. Yet, it is crucial to demonstrate the reversal of the heart failure-related pathophysiological manifestations, such as renin-angiotensin-aldosterone system activation (RAAS).

F4/80 Resident Macrophages Contribute to Cisplatin-Induced Renal Fibrosis.

Background: Cisplatin-induced kidney injury remains a major obstacle in utilizing cisplatin as a chemotherapeutic for solid-organ cancers. Thirty percent of patients treated with cisplatin develop acute kidney injury (AKI), and even patients who do not develop AKI are at risk for long-term declines in kidney function and development of chronic kidney disease (CKD). Modeling cisplatin-induced kidney injury in mice has revealed that repeated low doses of cisplatin lead to development of kidney fibrosis.

PON2 mediates mitochondrial dysfunction in tracheal epithelial cells in response to a quorum sensing molecule N-(-3-oxododecanoyl)-l-homoserine lactone.

The opportunistic bacterium Pseudomonas aeruginosa secretes the quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (C12) to co-ordinate gene expression profiles favorable for infection. Recent studies have demonstrated that high concentrations of C12 impair many aspects of host cell physiology, including mitochondrial function and cell viability. The cytotoxic effects of C12 are mediated by the lactonase enzyme, Paraoxonase 2 (PON2), which hydrolyzes C12 to a reactive metabolite.

Biomimetic cardiac tissue culture model (CTCM) to emulate cardiac physiology and pathophysiology ex vivo.

There is need for a reliable in vitro system that can accurately replicate the cardiac physiological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Here, we developed a cardiac tissue culture model (CTCM) that can electro-mechanically stimulate heart slices with physiological stretches in systole and diastole during the cardiac cycle.

Nrf2 transcriptional upregulation of IDH2 to tune mitochondrial dynamics and rescue angiogenic function of diabetic EPCs.

Endothelial progenitor cells (EPCs) are reduced in number and impaired in function in diabetic patients. Whether and how Nrf2 regulates the function of diabetic EPCs remains unclear. In this study, we found that the expression of Nrf2 and its downstream genes were decreased in EPCs from both diabetic patients and db/db mice.

Combining Community Wastewater Genomic Surveillance with State Clinical Surveillance: A Framework for SARS-CoV-2 Public Health Practice.

This study aimed to develop a framework for combining community wastewater surveillance with state clinical surveillance for the confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants within the community and to provide recommendations on how to expand on such research and apply the findings in public health responses. Wastewater samples were collected weekly from 17 geographically resolved locations in Louisville/Jefferson County, Kentucky (USA), from February 10 to December 13, 2021. Genomic surveillance and quantitative reverse transcription PCR (RT-qPCR) platforms were used to screen for SARS-CoV-2 in wastewater, and state clinical surveillance was used for confirmation.

Carnosine as a potential therapeutic for the management of peripheral vascular disease.

Aims: To evaluate the potential role of carnosine in the management of peripheral vascular disease.

Data Synthesis: Peripheral vascular disease is growing in its burden and impact; however it is currently under researched, and there are a lack of strong, non-invasive therapeutic options for the clinicians. Carnosine is a dipeptide stored particularly in muscle and brain tissue, which exhibits a wide range of physiological activities, which may be beneficial as an adjunct treatment for peripheral vascular disease.

Obesity and Fatty Acids Promote Mitochondrial Translocation of STAT3 Through ROS-Dependent Mechanisms.

Obesity promotes the onset and progression of metabolic and inflammatory diseases such as type 2 diabetes. The chronic low-grade inflammation that occurs during obesity triggers multiple signaling mechanisms that negatively affect organismal health. One such mechanism is the persistent activation and mitochondrial translocation of STAT3, which is implicated in inflammatory pathologies and many types of cancers.

Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles.

Background: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated.

Rigor Me This: What Are the Basic Criteria for a Rigorous, Transparent, and Reproducible Scientific Study?

Scientific advancement is predicated upon the ability of a novel discovery to be independently reproduced and substantiated by others. Despite this inherent necessity, the research community is awash in published studies that cannot be replicated resulting in widespread confusion within the field and waning trust from the general public. In many cases, irreproducibility is the unavoidable consequence of a study that is conducted without the appropriate degree of rigor, typified by fundamental flaws in approach, design, execution, analysis, interpretation, and reporting.

Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart.

Background Histidyl dipeptides such as carnosine are present in a micromolar to millimolar range in mammalian hearts. These dipeptides facilitate glycolysis by proton buffering. They form conjugates with reactive aldehydes, such as acrolein, and attenuate myocardial ischemia-reperfusion injury.

Influence of biological sex and exercise on murine cardiac metabolism.

Although the structural and functional effects of exercise on the heart are well established, the metabolic changes that occur in the heart during and after exercise remain unclear. In this study, we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise. After the exercise bout, we also recorded blood lactate, glucose, and ketone body levels and measured cardiac mitochondrial respiration.