Basic Science and Pathogenesis.

Background: This study was to elucidate the impact of blast-induced neurotrauma (BINT) on phosphoproteome networks and cognition in a genetically heterogeneous population of mice (rTg4510) with the human tau P301L mutation linked to Alzheimer's disease-related dementia (ADRD) including frontotemporal dementia.

Method: Mild traumatic brain injury was induced in rTg4510 mice exposed to a single low-density blast (LIB) at an upright position. After assessment of cognitive function by the automated-Home Cage Monitoring (aHCM) system, frontal cortex tissue was collected at 40 days post-injury.

LIM kinases in cardiovascular health and disease.

The Lim Kinase (LIMK) family of serine/threonine kinases is comprised of LIMK1 and LIMK2, which are central regulators of cytoskeletal dynamics via their well-characterized roles in promoting actin polymerization and destabilizing the cellular microtubular network. The LIMKs have been demonstrated to modulate several fundamental physiological processes, including cell cycle progression, cell motility and migration, and cell differentiation. These processes play important roles in maintaining cardiovascular health.

Thymidine Phosphorylase Promotes Abdominal Aortic Aneurysm via VSMC Modulation and Matrix Remodeling in Mice and Humans.

Thymidine phosphorylase (TYMP) promotes platelet activation and thrombosis while suppressing vascular smooth muscle cell (VSMC) proliferation. Both processes are central to the development and progression of abdominal aortic aneurysms (AAAs). We hypothesize that TYMP plays a role in AAA development.

Impact of Artificial Intelligence on Polyp Size and Surveillance Colonoscopy: A Phantom Study.

Background Artificial intelligence (AI) is a hot topic in the world of medicine. AI may be useful in identifying and sizing polyps, which influence surveillance intervals. Therefore, we examined polyp size estimation by AI using a survey study.

PI3K signaling and lysyl oxidase is critical to corneal stroma fibrosis following mustard gas injury.

Sulfur mustard gas (SM), an alkylating and vesicating agent, has been used frequently in many wars and conflicts. SM exposure to the eye results in several corneal abnormalities including scar/fibrosis formation. However, molecular mechanism for SM induced corneal fibrosis development is poorly understood.

Mineralocorticoid receptor antagonism prevents coronary microvascular dysfunction in intermittent hypoxia independent of blood pressure.

Study Objectives: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), and is associated with increased cardiovascular mortality that may not be reduced by standard therapies. Inappropriate activation of the renin-angiotensin-aldosterone system occurs in IH, and mineralocorticoid receptor (MR) blockade has been shown to improve vascular outcomes in cardiovascular disease. Thus, we hypothesized that MR inhibition prevents coronary and renal vascular dysfunction in mice exposed to chronic IH.

Prevention of Cardiovascular Disease in Women with Type 2 Diabetes: The Role of Incretin Mimetics and Sodium-Glucose Cotransporter-2 Inhibitors.

Cardiovascular disease (CVD) is the leading cause of death among individuals with type 2 diabetes (T2D), with women experiencing a disproportionate risk of events compared to men. Women have an amplified burden of cardiovascular risk factors once T2D is diagnosed. Incretin mimetics now play a central role in managing cardiovascular risk by improving glycemic control, promoting weight loss, and potentially exerting direct cardioprotective effects.

Pulsed electric field ablation as a candidate to enhance the anti-tumor immune response to immune checkpoint inhibitors.

Cancer ablation with pulsed electric fields (PEFs) involves the delivery of high-voltage, short-duration electrical pulses that destabilize tumor cells, leading to cellular death. Unlike most conventional ablation technologies, PEF ablation is non-thermal, allowing for safe and targeted energy delivery to the tumor without damaging surrounding tissue and critical structures. PEFs allow for specific dosing, predictable treatment zones, and preservation of the extracellular matrix and adjacent vascular tissues.

Anti-fibrotic effects of lisinopril (ACE inhibitor) and fasudil (ROCK inhibitor) in combination for canine corneal fibrosis in vitro.

Background: Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti-fibrotic effects of the FDA-approved drugs, angiotensin-converting enzyme inhibitor (ACE-I) lisinopril and rho-kinase inhibitor (ROCK-I) fasudil, alone and in combination, on the canine cornea using an established in vitro model.

Methods: To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (n = 20) were used.

Effect of insulin on indices of cerebral blood flow and cerebrovascular compliance in young adults.

Insulin has important vasodilatory effects in the peripheral circulation, but less is known about insulin's role in cerebrovascular control. Herein, we hypothesized both systemic (intravenous) and local (intranasal) insulin administration would increase indices of cerebral blood flow and reduce cerebrovascular compliance (Ci) in young adults. Participants were assigned to one of four separate protocols.

Role of epigenetics in corneal health and disease.

Epigenetics plays a vital role in corneal health and diseases. Epigenetic changes regulate the expression of genes by altering the accessibility of chromatin via histone modifications, DNA methylation and miRNAs without altering DNA sequence. Ocular trauma and infections are common causes of corneal damage, vision impairment, and mono/bilateral blindness worldwide.

Impact of dietary supplementation of glycocalyx precursors on vascular function in type 2 diabetes.

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGPs, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high-molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for 4 wk restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants.

EF24, a Curcumin Analog, Reverses Interleukin-18-Induced miR-30a or miR-342-Dependent TRAF3IP2 Expression, RECK Suppression, and the Proinflammatory Phenotype of Human Aortic Smooth Muscle Cells.

Curcumin, a polyphenolic compound derived from the widely used spice has shown anti-atherosclerotic effects in animal models and cultured vascular cells. Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells.

Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss.

Introduction: Tongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death.

Dopamine D2 receptors in the accumbal core region mediates the effects of fentanyl on sleep-wakefulness.

Fentanyl, a potent analgesic and addictive substance, significantly impacts sleep-wakefulness (S-W). Acutely, it promotes wake, whereas chronic abuse leads to severe sleep disruptions, including insomnia, which contributes to opioid use disorders (OUD), a chronic brain disease characterized by compulsive opioid use and harmful consequences. Although the critical association between sleep disruptions and fentanyl addiction is acknowledged, the precise mechanisms through which fentanyl influences sleep remain elusive.

Transcriptomic landscape of quiescent and proliferating human corneal stromal fibroblasts.

This study analyzed the transcriptional changes in primary human corneal stromal fibroblasts (hCSFs) grown under quiescent (serum-free) and proliferating (serum-supplemented) culture conditions to identify genes, pathways, and protein‒protein interaction networks influencing corneal repair and regeneration. Primary hCSFs were isolated from donor human corneas and maintained in serum-free or serum-laden conditions. RNA was extracted from confluent cultures using Qiagen kit and subjected to RNA sequencing (RNAseq) analysis.

Effect of endothelin-1 on the blood pressure response to acute hypoxia and hyperoxia in healthy young men.

Endothelin-1 (ET-1) and its receptors are linked to increases in sensitivity of the chemoreceptors to hypoxic stress and the development of hypertension in preclinical models. We hypothesized ET receptor antagonism would lower resting blood pressure (BP) as well as the acute BP response to chemoreflex stress. Twenty-four men (31 ± 5 years, 26 ± 3 kg/m) completed two study visits (control, bosentan).

Role of the peripheral chemoreceptors in cardiovascular and metabolic control in type 2 diabetes.

Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes (T2D) and the contribution of the peripheral chemoreceptors to resting cardiovascular and metabolic control. We hypothesized that: (1) adults with T2D exhibit exaggerated peripheral chemoreflex sensitivity; (2) the peripheral chemoreceptors contribute to cardiovascular dysfunction in T2D; and (3) attenuation of peripheral chemoreceptor activity improves glucose tolerance in T2D.

Enhanced ECCD36 signaling promotes skeletal muscle insulin resistance in female mice.

Consumption of a Western diet (WD) increases CD36 expression in vascular, hepatic, and skeletal muscle tissues promoting lipid metabolic disorders and insulin resistance. We further examined the role of endothelial cell-specific CD36 (ECCD36) signaling in contributing to skeletal muscle lipid metabolic disorders, insulin resistance, and their underlying molecular mechanisms. Female ECCD36 wild-type (ECCD36) and knock-out (ECCD36) mice, aged 6 wk, were provided with either a WD or a standard chow diet for a duration of 16 wk.

Integrating molecular and cellular components of endothelial shear stress mechanotransduction.

The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces (i.e.