Hindbrain catecholamine regulation of ventromedial hypothalamic nucleus glycogen metabolism during acute versus recurring insulin-induced hypoglycemia in male versus female rat.

Ventromedial hypothalamic nucleus (VMN) glycogen metabolism affects local glucoregulatory signaling. The hindbrain metabolic-sensitive catecholamine (CA) neurotransmitter norepinephrine controls VMN glycogen phosphorylase (GP)-muscle (GPmm) and -brain (GPbb) type expression in male rats. Present studies addressed the premise that CA regulation of hypoglycemic patterns of VMN glycogen metabolic enzyme protein expression is sex-dimorphic, and that this signal is responsible for sex differences in acclimation of these profiles to recurrent insulin-induced hypoglycemia (RIIH).

Ventromedial hypothalamic nucleus glycogen regulation of metabolic-sensory neuron AMPK and neurotransmitter expression: role of lactate.

Astrocyte glycogen is dynamically remodeled during metabolic stability and provides oxidizable l-lactate equivalents during neuroglucopenia. Current research investigated the hypothesis that ventromedial hypothalamic nucleus (VMN) glycogen metabolism controls glucostimulatory nitric oxide (NO) and/or glucoinhibitory gamma-aminobutyric acid (GABA) neuron 5'-AMP-activated protein kinase (AMPK) and transmitter marker, e.g.

Restoring the endothelial barrier function in the elderly.

Endothelial barrier dysfunction in the elderly has been associated with severe disorders, including acute respiratory distress syndrome, sepsis and COVID-19. Herein we deliver an opinion regarding the development of alternative therapeutic avenues to counteract the pathogenesis of the corresponding diseases.

Unfolded Protein Response: A Regulator of the Endothelial Barrier.

Recent evidence suggest that the endothelial barrier function is enhanced by the mild activation of the unfolded protein response (UPR), which aims to suppress abnormal increases of endoplasmic reticulum stress. Heat shock protein 90 inhibitors and growth hormone releasing hormone antagonists exert the capacity to activate this multifaceted cellular mechanism (UPR). Thus, investigations on the signalling network involved in those events, may deliver exciting opportunities in diseases related to endothelial barrier dysfunction.

Growth Hormone Releasing Hormone in Endothelial Barrier Function.

Growth hormone releasing hormone (GHRH) is the integral regulator of the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis. It exerts mitogenic effects in a plethora of progressive cancers. Recent evidence suggests the emerging role of that 44-amino acid (aa) neuropeptide in lung endothelial barrier function (EBF), which will be discussed herein.

Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance.

This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software.

Aiming student pharmacist organizations toward professional success: Mapping student activities to a professional development program.

Introduction: This project describes the mapping of the Accreditation Council for Pharmacy Education (ACPE) Accreditation Standards to activities of a student pharmacist organization and to assess student perceptions of the process' utility in completing a professional growth and development program (PGDP).

Methods: A list of activities from the student pharmacist organization for academic year 2018-2019 was compiled at the start of each semester. ACPE Standards 3 and 4 were mapped to each chapter activity using a spreadsheet.

Insights on supporting the aging brain microvascular endothelium.

Blood brain barrier hyperpermeability has been associated with age-related affective disorders, including depression, mania, anxiety, Alzheimer's and Parkinson's disease. Our recent efforts suggest that a promising therapeutic approach may arise due to the activation of the unfolded protein response (UPR) element in the affected tissues. Growth hormone releasing hormone antagonists and heat shock protein 90 inhibitors have been shown to induce UPR.

Identification of new fisetin analogs as kinase inhibitors: Data on synthesis and anti-skin cancer activities evaluation.

This article contains supplemental datasets of the recently published related research article by Roy et al., [1]. It provides in-depth data not included in the original co-submission on the biophysical, molecular docking, and biological characterization of newly synthesized flavonol-based analogs of fisetin, a natural dietary small molecule with anticancer and anti-inflammatory properties.

Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases.

Lung cancer (LC) and pancreatic cancer (PC) are the first and fourth leading causes of cancer‑related deaths in the US. Deregulated cell cycle progression is the cornerstone for rapid cell proliferation, tumor development, and progression. Here, we provide evidence that a novel combinatorial miR treatment inhibits cell cycle progression at two phase transitions, through their activity on the CDK4 and CDK1 genes.

Sex differences in ventromedial hypothalamic nucleus glucoregulatory transmitter biomarker protein during recurring insulin-induced hypoglycemia.

Recurring insulin-induced hypoglycemia (RIIH) in males correlates with maladaptive glucose counter-regulatory collapse and acclimated expression of ventromedial hypothalamic nucleus (VMN) nitric oxide (NO) and γ-aminobutyric acid (GABA) metabolic transmitter biomarkers, e.g., neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase (GAD).

Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress.

The brain endothelium is an integral element of the blood-brain barrier (BBB). Dysfunction of this formation due to increased generation of reactive oxygen species (ROS) progresses the establishment of neurological disorders including stroke and traumatic brain injury. Heat shock protein 90 inhibitors are anti-inflammatory agents, and their activities are mediated, at least in part, by P53.

Neuroestradiol regulation of ventromedial hypothalamic nucleus 5'-AMP-activated protein kinase activity and counterregulatory hormone secretion in hypoglycemic male versus female rats.

Hypoglycemia activates the ultra-sensitive energy gauge 5'-AMP-activated protein kinase (AMPK) in ventromedial hypothalamic nucleus (VMN) gluco-regulatory neurons. The VMN is exemplified by high levels of expression of the enzyme aromatase, which converts testosterone to estradiol. This study examined the hypothesis that neuroestradiol imposes sex-dimorphic control of VMN AMPK activity during eu- and/or hypoglycemia.

Cancer Vaccines, Treatment of the Future: With Emphasis on HER2-Positive Breast Cancer.

Breast cancer is one of the leading causes of death in women. With improvements in early-stage diagnosis and targeted therapies, there has been an improvement in the overall survival rate in breast cancer over the past decade. Despite the development of targeted therapies, tyrosine kinase inhibitors, as well as monoclonal antibodies and their toxin conjugates, all metastatic tumors develop resistance, and nearly one-third of HER2+ breast cancer patients develop resistance to all these therapies.

HPLC-electrospray ionization-mass spectrometry optimization by high-performance design of experiments for astrocyte glutamine measurement.

The amino acid glutamine (Gln) is a likely source of energy in the brain during neuroglucopenia. Effects of glucose deficiency on astrocyte Gln homeostasis remain unclear, as analytical tools of requisite sensitivity for quantification of intracellular levels of this molecule are not currently available. Here, a primary hypothalamic astrocyte culture model was used in conjunction with design of experiments (DOE)-refined high-performance liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) methodology to investigate the hypothesis that glucoprivation alters astrocyte Gln content in a sex-specific manner.

Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Astrocyte Glycogen Metabolism.

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR).

Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers.

Due to hurdles, including resistance, adverse effects, and poor bioavailability, among others linked with existing therapies, there is an urgent unmet need to devise new, safe, and more effective treatment modalities for skin cancers. Herein, a series of flavonol-based derivatives of fisetin, a plant-based flavonoid identified as an anti-tumorigenic agent targeting the mammalian targets of rapamycin (mTOR)-regulated pathways, were synthesized and fully characterized. New potential inhibitors of receptor tyrosine kinases (c-KITs), cyclin-dependent kinase-2 (CDK2), and mTOR, representing attractive therapeutic targets for melanoma and non-melanoma skin cancers (NMSCs) treatment, were identified using inverse-docking, in vitro kinase activity and various cell-based anticancer screening assays.

Unfolded protein response in the COVID-19 context.

The unfolded protein response (UPR) maintains cellular homeostasis by regulating key elements of cellular growth and defense. Recent evidence suggests that this mechanism affects the vascular barrier function, by modulating lung endothelial permeability. Dysregulation of this barrier contributes in the irreversible outcomes of the SARS-CoV-2 - inflicted acute respiratory distress syndrome (ARDS).

Metformin in acute respiratory distress syndrome: An opinion.

Senior individuals are more susceptible to the irreversible outcomes of endothelial barrier dysfunction, the hallmark of Acute Respiratory Distress Syndrome (ARDS). The Severe Acute Respiratory Syndrome Coronovirus 2 (SARS-CoV-2) - inflicted ARDS delivers the devastating outcomes of the COVID-19 worldwide. Endothelial hyperpermeability has been associated with both the progression and establishment of the COVID-19 - related respiratory failure.

Sex-dimorphic neuroestradiol regulation of ventromedial hypothalamic nucleus glucoregulatory transmitter and glycogen metabolism enzyme protein expression in the rat.

Background: Ventromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression.

Methods: The aromatase inhibitor letrozole (LZ) was used with high-resolution microdissection/Western blot techniques to address the hypothesis that neuroestradiol exerts sex-dimorphic control of VMN neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase (GAD) protein expression.

Sex-dimorphic Rostro-caudal Patterns of 5'-AMP-activated Protein Kinase Activation and Glucoregulatory Transmitter Marker Protein Expression in the Ventrolateral Ventromedial Hypothalamic Nucleus (VMNvl) in Hypoglycemic Male and Female Rats: Impact of Estradiol.

The ventromedial hypothalamic nucleus-ventrolateral part (VMNvl) is an estradiol-sensitive structure that controls sex-specific behavior. Electrical reactivity of VMNvl neurons to hypoglycemia infers that cellular energy stability is monitored there. Current research investigated the hypothesis that estradiol elicits sex-dimorphic patterns of VMNvl metabolic sensor activation and gluco-regulatory neurotransmission during hypoglycemia.

Involvement of the unfolded protein response in the protective effects of growth hormone releasing hormone antagonists in the lungs.

Growth hormone releasing hormone (GHRH) antagonists enhance endothelial barrier function and counteract the LPS-induced lung endothelial hyperpermeability, the cardinal feature of the acute respiratory distress syndrome (ARDS). The unfolded protein response (UPR) is a multifaceted molecular mechanism, strongly involved in tissue defense against injury. The current study introduces the induction of UPR by GHRH antagonists, since those peptides induced several UPR activation markers, including the inositol-requiring enzyme-1α (IRE1α), the protein kinase RNA-like ER kinase (PERK), and the activating transcription factor 6 (ATF6).

Norepinephrine Regulation of Adrenergic Receptor Expression, 5' AMP-Activated Protein Kinase Activity, and Glycogen Metabolism and Mass in Male Versus Female Hypothalamic Primary Astrocyte Cultures.

Norepinephrine (NE) control of hypothalamic gluco-regulation involves astrocyte-derived energy fuel supply. In male rats, exogenous NE regulates astrocyte glycogen metabolic enzyme expression through 5'-AMP-activated protein kinase (AMPK)-dependent mechanisms. Current research utilized a rat hypothalamic astrocyte primary culture model to investigate the premise that NE imposes sex-specific direct control of AMPK activity and glycogen mass and metabolism in these glia.