Oral administration of ethinyl estradiol and the brain-selective estrogen prodrug DHED in a female common marmoset model of menopause: Effects on cognition, thermoregulation, and sleep.

Menopausal symptoms of sleep disturbances, cognitive deficits, and hot flashes are understudied, in part due to the lack of animal models in which they co-occur. Common marmosets (Callithrix jacchus) are valuable nonhuman primates for studying these symptoms, and we examined changes in cognition (reversal learning), sleep (48 h/wk of sleep recorded by telemetry), and thermoregulation (nose temperature in response to mild external warming) in middle-aged, surgically-induced menopausal marmosets studied at baseline, during 3-week phases of ethinyl estradiol (EE, 4 μg/kg/day, p.o.

Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia.

Background: Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation.

Results: Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy. The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via selective disruption of pro-survival mTOR signaling.

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer.

Background: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.

Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice.

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL.

Estradiol influences adenosinergic signaling and nonrapid eye movement sleep need in adult female rats.

Gonadal steroids and gender are risk factors for sleep disruptions and insomnia in women. However, the relationship between ovarian steroids and sleep is poorly understood. In rodent models, estradiol (E2) suppresses sleep in females suggesting that E2 may reduce homeostatic sleep need.

Prenatal Kynurenine Elevation Elicits Sex-Dependent Changes in Sleep and Arousal During Adulthood: Implications for Psychotic Disorders.

Dysregulation of the kynurenine pathway (KP) of tryptophan catabolism has been implicated in psychotic disorders, including schizophrenia and bipolar disorder. Kynurenic acid (KYNA) is a KP metabolite synthesized by kynurenine aminotransferases (KATs) from its biological precursor kynurenine and acts as an endogenous antagonist of N-methyl-D-aspartate and α7-nicotinic acetylcholine receptors. Elevated KYNA levels found in postmortem brain tissue and cerebrospinal fluid of patients are hypothesized to play a key role in the etiology of cognitive symptoms observed in psychotic disorders.

Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization.

Effective radiation treatment (RT) for recurrent nasopharyngeal cancers (NPC), featuring an intrinsic hypoxic sub-volume, remains a clinical challenge. Lack of disease-specific models of NPC, together with difficulties in establishing patient derived xenograft (PDX) models, have further hindered development of personalized therapeutic options. Herein, we established two NPC organoid lines from recurrent NPC PDX models and further characterized and compared these models with original patient tumors using RNA sequencing analysis.

Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus (EBV), which is highly prevalent in South China, Southeast Asia, and North Africa. Despite being a highly radio-sensitive and treatable cancer, a majority of NPC patients are diagnosed in their advanced stage, and locoregional and distant relapses following definitive treatment contribute largely to cancer-specific mortality among these patients. Given that EBV-driven NPC is the predominant variant seen in endemic regions, various EBV detection methods have been developed and are utilized in screening, prognostication, and post-treatment surveillance of NPC patients.

Sex, Drugs, and the Medial Amygdala: A Model of Enhanced Sexual Motivation in the Female Rat.

Methamphetamine (METH) is a psychomotor stimulant that is reported to enhance sexual desire and behavior in both men and women, leading to increases in unplanned pregnancies, sexually-transmitted infections, and even comorbid psychiatric conditions. Here, we discuss our rodent model of increased sexually-motivated behaviors in which the co-administration of METH and the ovarian hormones, estradiol and progesterone, intensify the incentive properties of a sexual stimulus and increases measures of sexually-motivated behavior in the presence of an androgen-specific cue. We then present the neurobiological mechanisms by which this heightened motivational salience is mediated by the actions of METH and ovarian hormones, particularly progestins, in the posterodorsal medial nucleus of the amygdala (MePD), a key integration site for sexually-relevant sensory information with generalized arousal.

Adsorption of 4--Nonylphenol, Carvacrol, and Ethanol onto Iron Oxide from Nonaqueous Hydrocarbon Solvents.

The adsorption of 4--nonylphenol (4NP), carvacrol, and ethanol onto the surface of iron oxide from nonaqueous solutions is presented. It is found that adsorption of 4NP from alkanes is strong and proceeds to monolayer formation, where the molecules are essentially "upright". However, at high relative concentrations, ethanol successfully out-competes 4NP for the iron oxide surface.

Neuroendocrine Control of Sleep.

Sleep is a phenomenon in animal behavior as enigmatic as it is ubiquitous, and one deeply tied to endocrine function. Though there are still many unanswered questions about the neurochemical basis of sleep and its functions, extensive interactions have been identified between sleep and the endocrine system, in both the endocrine system's effect on sleep and sleep's effect on the endocrine system. Unfortunately, until recent years, much research on sleep behavior largely disregarded its connections with the endocrine system.

Sex differences in hearing: Probing the role of estrogen signaling.

Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans.

Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate.

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects, including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI letrozole (20 μg, p.

A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats.

The kynurenine pathway (KP) of tryptophan degradation has been implicated in psychiatric disorders. Specifically, the astrocyte-derived metabolite kynurenic acid (KYNA), an antagonist at both N-methyl-d-aspartate (NMDA) and α7 nicotinic acetylcholine (α7nACh) receptors, has been implicated in cognitive processes in health and disease. As KYNA levels are elevated in the brains of patients with schizophrenia, a malfunction at the glutamatergic and cholinergic receptors is believed to be causally related to cognitive dysfunction, a core domain of the psychopathology of the illness.

Methamphetamine alters DNMT and HDAC activity in the posterior dorsal medial amygdala in an ovarian steroid-dependent manner.

Methamphetamine (Meth) is a psychomotor stimulant associated with increased sexual drive and risky sexual behaviors in both men and women. Females are comparatively understudied, despite the fact that are just as likely as men to use methamphetamine. Importantly, Meth-associated sexual behaviors put female-users at a greater risk for unplanned pregnancies, and increase the risk of psychiatric co-morbidities such as depression.

Sex Differences in Hippocampal Memory and Kynurenic Acid Formation Following Acute Sleep Deprivation in Rats.

Inadequate sleep is a prevalent problem within our society that can result in cognitive dysfunction. Elevations in kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation known to impact cognition, in the brain may constitute a molecular link between sleep loss and cognitive impairment. To test this hypothesis, we investigated the impact of 6 hours of sleep deprivation on memory and KP metabolism (brain and plasma) in male and female rats.

Size-Based Enrichment Technologies for Non-cancerous Tumor-Derived Cells in Blood.

Enumeration of circulating tumor cells (CTCs) in the bloodstream can predict prognosis and survival in cancer patients. However, CTC rarity and heterogeneity pose challenges in using them as biomarkers. Recent publications have reported new classes of circulating, non-cancerous tumor-derived cells present in cancer patients but not in healthy controls; these include cancer-associated macrophages, tumor-endothelial clusters (TECs), and cancer-associated fibroblasts (CAFs).

The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice.

Background: Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice.

Methods: Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.

The Role of Ovarian Hormones and the Medial Amygdala in Sexual Motivation.

Purpose: Although research into the neurobiology of sexual desire in women is active, relatively little is understood about the origins of sexual motivation in women. The purpose of our review is to discuss factors that influence a central sexual motivate state and generalized arousal as potential drivers of sexual motivation in women and female rats.

Recent Findings: Sexual motivation is the product of interactions of the central motive state and salient sexually-relevant cues.

Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats.

Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality.