Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis.

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis.

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (NaSeO) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + NaSeO (2 mg/kg), and AMPH + PDG + NaSeO.

Neuroprotective Effect of Morin Hydrate against Attention-Deficit/Hyperactivity Disorder (ADHD) Induced by MSG and/or Protein Malnutrition in Rat Pups: Effect on Oxidative/Monoamines/Inflammatory Balance and Apoptosis.

Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD).

Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer's Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression.

Mobile-Based Augmented Reality Application in Pharmacy Schools Implemented in Pharmaceutical Compounding Laboratories: Students' Benefits and Reception.

Background: Augmented reality (AR) is a technological approach which combines virtual objects such as text, pictures or videos with physical objects (real-world). The study aimed to design, implement and validate a mobile-based AR application, as a self-paced, interactive, student-centered learning tool be used in the pharmaceutical compounding laboratory course for first year pharmacy students.

Method: A mobile-based AR application (Amplified Rx app; HeyPayLess Inc) compatible with iOS and android operating system was developed.

Single-cell multiplex qPCR evidence for sex-dimorphic glutamate decarboxylase, estrogen receptor, and 5'-AMP-activated protein kinase alpha subunit mRNA expression by ventromedial hypothalamic nucleus GABAergic neurons.

The inhibitory amino acid transmitter γ-aminobutryic acid (GABA) acts within the ventromedial hypothalamus to regulate systemic glucose homeostasis, but the issue of whether this neurochemical signal originates locally or is supplied by afferent innervation remains controversial. Here, combinatory in situ immunocytochemistry/laser-catapult microdissection/single-cell multiplex qPCR techniques were used to investigate the premise that ventromedial hypothalamic nucleus ventrolateral (VMNvl) and/or dorsomedial (VMNdm) division neurons contain mRNAs that encode glutamate decarboxylase (GAD) or GAD and metabolic-sensory biomarkers, and that expression of these genes is sex-dimorphic. In male and female rats, GAD mRNA was elevated in VMNvl versus VMNdm GAD-immunopositive (-ir) neurons, yet the female exhibited higher GAD transcript content in VMNdm versus VMNvl GABAergic nerve cells.

Glycogen phosphorylase isoform regulation of glucose and energy sensor expression in male versus female rat hypothalamic astrocyte primary cultures.

Astrocyte glycogen constitutes the primary energy fuel reserve in the brain. Current research investigated the novel premise that glycogen turnover governs astrocyte responsiveness to critical metabolic and neurotransmitter (norepinephrine) regulatory signals in a sex-dimorphic manner. Here, rat hypothalamic astrocyte glycogen phosphorylase (GP) gene expression was silenced by short-interfering RNA (siRNA) to investigate how glycogen metabolism controlled by GP-brain type (GPbb) or GP-muscle type (GPmm) activity affects glucose [glucose transporter-2 (GLUT2)] and energy [5'-AMP-activated protein kinase (AMPK)] sensor and adrenergic receptor (AR) proteins in each sex.

Effects of short-term food deprivation on catecholamine and metabolic-sensory biomarker gene expression in hindbrain A2 noradrenergic neurons projecting to the forebrain rostral preoptic area: Impact of negative versus positive estradiol feedback.

Hindbrain A2 noradrenergic neurons assimilate estrogenic and metabolic cues. In female mammals, negative- versus positive-feedback patterns of estradiol (E) secretion impose divergent regulation of the gonadotropin-releasing hormone (GnRH)-pituitary-gonadal (HPG) neuroendocrine axis. Current research used retrograde tracing, dual-label immunocytochemistry, single-cell laser-microdissection, and multiplex qPCR methods to address the premise that E feedback modes uniquely affect metabolic regulation of A2 neurons involved in HPG control.

p53 missense mutant G242A subverts natural killer cells in sheltering mouse breast cancer cells against immune rejection.

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault.

Hindbrain lactate regulation of hypoglycemia-associated patterns of catecholamine and metabolic-sensory biomarker gene expression in A2 noradrenergic neurons innervating the male versus female ventromedial hypothalamic nucleus.

Caudal hindbrain A2 noradrenergic neurons provide critical metabolic-sensory input to the brain glucostatic circuitry. In males, insulin-induced hypoglycemia (IIH)-associated patterns of A2 cell dopamine-beta-hydroxylase (DβH) protein expression reflect diminution of the oxidizable fuel L-lactate, yet DβH exhibits sex-dimorphic responses to IIH. Here, retrograde tracing and combinatory single-cell laser-microdissection/multiplex qPCR techniques were used to examine whether lactate imposes sex-specific control of hypoglycemia-associated metabolic-sensory function and noradrenergic neurotransmission in A2 neurons that innervate the ventromedial hypothalamic nucleus (VMN), a key glucose-regulatory structure.

The Tobacco β-Cembrenediol: A Prostate Cancer Recurrence Suppressor Lead and Prospective Scaffold via Modulation of Indoleamine 2,3-Dioxygenase and Tryptophan Dioxygenase.

Prostate cancer (PC) is the second leading cause of death in men in the US. PC has a high recurrence rate, and limited therapeutic options are available to prevent disease recurrence. The tryptophan-degrading enzymes 2,3-indoleamine dioxygenase (IDO1) and tryptophan dioxygenase (TDO2) are upregulated in invasive PC.

Selenium Nanoparticles with Prodigiosin Rescue Hippocampal Damage Associated with Epileptic Seizures Induced by Pentylenetetrazole in Rats.

Background: Prodigiosin (PDG) is a red pigment synthesized by bacterial species with important pharmaceutical and biological activities. Here, we investigated the neuroprotective and anticonvulsant activities of green biosynthesized selenium formulations with PDG (SeNPs-PDG) versus pentylenetetrazole (PTZ)-induced epileptic seizures.

Methods: Rats were assigned into six experimental groups: control; PTZ (60 mg/kg, epileptic model); sodium valproate (200 mg/kg) + PTZ; PDG (300 mg/kg) + PTZ; sodium selenite (0.

Student Performance on Graded Versus Ungraded Readiness Assurance Tests in a Team-Based Learning Elective.

Team-based learning is widely used in pharmacy education. In this context, students need to be incentivized to do preclass preparation, thus ensuring they are ready for team-based learning, via graded readiness assurance tests (RATs). The purpose of this study was to determine the effect of graded versus ungraded RATs on examination performance in an ambulatory care elective course for third-year student pharmacists.

Neuroprotective Efficiency of Prodigiosins Conjugated with Selenium Nanoparticles in Rats Exposed to Chronic Unpredictable Mild Stress is Mediated Through Antioxidative, Anti-Inflammatory, Anti-Apoptotic, and Neuromodulatory Activities.

Purpose: Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats.

Pharmacological Investigation of CC-LAAO, an L-Amino Acid Oxidase from Snake Venom.

Snake venom proteins, which are responsible for deadly snakebite envenomation, induce severe injuries including neurotoxicity, myotoxicity, cardiotoxicity, hemorrhage, and the disruption of blood homeostasis. Yet, many snake-venom proteins have been developed as potential drugs for treating human diseases due to their pharmacological effects. In this study, we evaluated the use of, an L-amino acid oxidase isolated from snake venom CC-LAAO, as a potential anti-glioblastoma drug, by investigating its in vivo and in vitro pharmacological effects.

PCSK9 Axis-Targeting Pseurotin A as a Novel Prostate Cancer Recurrence Suppressor Lead.

Prostate cancer (PC) is the most common malignancy and the second leading cause of cancer death in men. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the cholesterol metabolism by regulating the LDL receptor (LDLR) degradation. The PCSK9 axis is proved to be a potential novel therapeutic target in multiple cancer types.

Peptides and peptidomimetics as therapeutic agents for Covid-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Covid-19 pandemic has caused high morbidity and mortality rates worldwide. Virus entry into cells can be blocked using several strategies, including inhibition of protein-protein interactions (PPIs) between the viral spike glycoprotein and cellular receptors, as well as blocking of spike protein conformational changes that are required for cleavage/activation and fusogenicity. The spike-mediated viral attachment and entry into cells via fusion of the viral envelope with cellular membranes involve PPIs mediated by short peptide fragments exhibiting particular secondary structures.

A pH-sensitive liposome formulation of a peptidomimetic-Dox conjugate for targeting HER2 + cancer.

Cancer treatment faces the challenge of selective delivery of the cytotoxic drug to the desired site of action to minimize undesired side effects. The liposomal formulation containing targeting ligand conjugated cytotoxic drug can be an effective approach to specifically deliver chemotherapeutic drugs to cancer cells that overexpress a particular cell surface receptor. This research focuses on the in vitro and in vivo studies of a peptidomimetic ligand attached doxorubicin for the HER2 positive lung and breast cancer cells transported by a pH-dependent liposomal formulation system for the enhancement of targeted anticancer treatment.

Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men.

The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients.

Louisiana Medicaid access for treatment and care for hepatitis C virus (LA-MATCH) project: A cross-sectional study protocol.

Introduction: This article presents the Louisiana Hepatitis C Elimination Program's evaluation protocol underway at the Louisiana State University Health Sciences Center-New Orleans. With the availability of direct-acting antiviral (DAA) agents, the elimination of Hepatitis C (HCV) has become a possibility. The HCV Elimination Program was initiated by the Louisiana Department of Health (LDH) Office of Public Health (OPH), LDH Bureau of Health Services Financing (Medicaid), and the Louisiana Department of Public Safety and Corrections (DPSC) to provide HCV treatment through an innovative pricing arrangement with Asegua Therapeutics, whereby a fixed cost is set for a supply of treatment over five years.

Identification of genetic modifiers of lifespan on a high sugar diet in the Genetic Reference Panel.

Genome-wide association studies (GWAS) have become beneficial in identifying genetic variants underlying susceptibility to various complex diseases and conditions, including obesity. Utilizing the Genetic Reference Panel (DGRP), we performed a GWAS of lifespan of 193 genetically distinct lines on a high sugar diet (HSD). The DGRP analysis pipeline determined the most significant lifespan associated polymorphisms were within loci of genes involved in: neural processes, behavior, development, and apoptosis, among other functions.

Comparative Gene Signature of (-)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights.

Triple negative breast cancer (TNBC) heterogeneity and limited therapeutic options confer its phenotypic aggressiveness. The discovery of anti-TNBC natural products with valid molecular target(s) and defined pharmacodynamic profile would facilitate their therapeutic nutraceutical use by TNBC patients. The extra-virgin olive oil (EVOO) is a key Mediterranean diet ingredient.