5-HT receptor activation produces rapid antidepressant-like effects in rodents.

Ketamine is noted for its rapid onset antidepressant response and effectiveness in patients with treatment resistant depression. While most research has focused on glutamatergic mechanisms, recent studies show that antidepressant-like effects in rodents are dependent upon the serotonergic (5-HT) system and suggest a potential contribution of the 5-HT receptor. In this study we utilized CP-94253 to examine whether 5-HT receptor agonism produces rapid and sustained antidepressant-like effects, focusing on rodent models and treatment approaches commonly used to demonstrate the differentiated response to ketamine.

TAAR1 and 5-HT receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid.

Despite the rising prevalence of autism spectrum disorder (ASD), there remains a significant unmet need for pharmacotherapies addressing its core and associative symptoms. While some atypical antipsychotics have been approved for managing associated irritability and aggression, their use is constrained by substantial side effects. This study aimed firstly to develop behavioral measures to explore frustration, irritability and aggression phenotypes in the rat prenatal valproic acid (VPA) model of ASD.

TAAR1 agonists improve glycemic control, reduce body weight and modulate neurocircuits governing energy balance and feeding.

Objective: Metabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 (TAAR1) have potential as a new treatment option for schizophrenia. Intriguingly, preclinical tudies have also identified TAAR1 as a novel regulator of metabolic control.

A Meta-Analysis of the Antidepressant Responses in Pivotal Trials on Esketamine Nasal Spray and Atypical Antipsychotics.

Purpose: This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant outcomes.

Patients And Methods: Data were extracted from 12 trials of ESK-NS or AAPs in depressed patients (4276) with inadequate response or resistance to conventional antidepressants. Montgomery-Åsberg Depression Rating Scale (MADRS) score reductions from baseline and response rates (≥50% reduction) were analyzed.

On the use of partitioning for scheduling of surgeries in the inpatient surgical department.

In hospitals, the efficient planning of the operating rooms (ORs) is difficult due to the uncertainty inherent to surgical services. This is especially true for the inpatient surgical department where complex and long surgeries are often performed along with surgeries on emergency patients. This paper aims to improve the scheduling of the inpatient department by partitioning the elective surgeries into the more predictable surgeries (MPS) group and the less predictable surgeries (LPS) group, based on surgery duration variability, and by scheduling each of the two surgery groups in different ORs.

Putative role of GPR139 on sleep modulation using pharmacological and genetic rodent models.

GPR139 is a G-protein coupled receptor expressed in circumventricular regions of the habenula and septum. Amino acids L-tryptophan and L-phenylalanine have been shown to activate GPR139 at physiologically relevant concentrations. The aim of the present study was to investigate the role of GPR139 on sleep modulation using pharmacological and genetic (GPR139 knockout mice, KO) rodent models.

The PAR2 signal peptide prevents premature receptor cleavage and activation.

Unlike closely related GPCRs, protease-activated receptors (PAR1, PAR2, PAR3, and PAR4) have a predicted signal peptide at their N-terminus, which is encoded by a separate exon, suggesting that the signal peptides of PARs may serve an important and unique function, specific for PARs. In this report, we show that the PAR2 signal peptide, when fused to the N-terminus of IgG-Fc, effectively induced IgG-Fc secretion into culture medium, thus behaving like a classical signal peptide. The presence of PAR2 signal peptide has a strong effect on PAR2 cell surface expression, as deletion of the signal peptide (PAR2ΔSP) led to dramatic reduction of the cell surface expression and decreased responses to trypsin or the synthetic peptide ligand (SLIGKV).

A Natural Product with High Affinity to Sigma and 5-HT Receptors as Novel Therapeutic Drug for Negative and Cognitive Symptoms of Schizophrenia.

Dehydrocorybulbine (DHCB), an alkaloid from Corydalis yanhusuo. W.T, has been identified as a dopamine receptor antagonist.

Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC).

Purpose: No study has investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any patients with early-stage cancer. This study (DYNAMIC) investigated perioperative dynamic changes in ctDNA and determined the appropriate detection time of ctDNA-based surveillance for surgical patients with lung cancer. Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391).

GPR139 and Dopamine D2 Receptor Co-express in the Same Cells of the Brain and May Functionally Interact.

GPR139, a G-coupled receptor that is activated by the essential amino acids L-tryptophan and L-phenylalanine, is predominantly expressed in the brain and pituitary. The physiological function of GPR139 remains elusive despite the availability of pharmacological tool agonist compounds and knock-out mice. Whole tissue RNA sequencing data from human, mouse and rat tissues revealed that GPR139 and the dopamine D receptor (DRD2) exhibited some similarities in their distribution patterns in the brain and pituitary gland.

Mutagenesis of GPR139 reveals ways to create gain or loss of function receptors.

GPR139 is a Gq-coupled receptor activated by the essential amino acids L-tryptophan (L-Trp) and L-phenylalanine (L-Phe). We carried out mutagenesis studies of the human GPR139 receptor to identify the critical structural motifs required for GPR139 activation. We applied site-directed and high throughput random mutagenesis approaches using a double addition normalization strategy to identify novel GPR139 sequences coding receptors that have altered sensitivity to endogenous ligands.

Melanin concentrating hormone modulates oxytocin-mediated marble burying.

Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying.

The Antinociceptive Properties of the Corydalis yanhusuo Extract.

Corydalis yanhusuo. W.T.

Inactivation of the melanin concentrating hormone system impairs maternal behavior.

In order to prepare the mother for the demands of pregnancy and lactation, the maternal brain is subjected to a number of adaptations. Maternal behaviors are regulated by complex neuronal interactions. Here, we show that the melanin concentrating hormone (MCH) system is an important regulator of maternal behaviors.

A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity.

Background: Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whether methionine administration could lead to behavioral changes that reflect schizophrenic symptoms in mice.

Amide alkaloids from Scopolia tangutica.

Four new hydroxycinnamic acid amides, scotanamines A-D (1-4), and seven known alkaloids, including N (1),N (10)-di-dihydrocaffeoylspermidine (5), scopolamine (6), anisodamine (7), hyoscyamine (8), anisodine (9), caffeoylputrescine (10), and N (1)-caffeoyl-N (3)-dihydrocaffeoylspermidine (11), were obtained from the roots of Scopolia tangutica. The present study represents the first recognition of hydroxycinnamic acid amides containing putrescine or spermidine in S. tangutica.

Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons.

Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI), but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated.

Histamine inhibits the melanin-concentrating hormone system: implications for sleep and arousal.

Melanin-concentrating hormone (MCH)-producing neurons are known to regulate a wide variety of physiological functions such as feeding, metabolism, anxiety and depression, and reward. Recent studies have revealed that MCH neurons receive projections from several wake-promoting brain regions and are integral to the regulation of rapid eye movement (REM) sleep. Here, we provide evidence in both rats and mice that MCH neurons express histamine-3 receptors (H3R), but not histamine-1 (H1R) or histamine-2 (H2R) receptors.

Semi-automatic segmentation and classification of Pap smear cells.

Cytologic screening has been widely used for detecting the cervical cancers. In this study, a semiautomatic PC-based cellular image analysis system was developed for segmenting nuclear and cytoplasmic contours and for computing morphometric and textual features to train support vector machine (SVM) classifiers to classify four different types of cells and to discriminate dysplastic from normal cells. A software program incorporating function, including image reviewing and standardized denomination of file names, was also designed to facilitate and standardize the workflow of cell analyses.

A novel analgesic isolated from a traditional Chinese medicine.

Background: Current pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.

Results: In a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain.

Anatomical characterization of bombesin receptor subtype-3 mRNA expression in the rodent central nervous system.

Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein-coupled receptor (GPCR) involved in the regulation of energy homeostasis. Mice deficient in BRS-3 develop late-onset mild obesity with metabolic defects, while synthetic agonists activating BRS-3 show antiobesity profiles by inhibiting food intake and increasing metabolic rate in rodent models. The molecular mechanisms and the neural circuits responsible for these effects, however, remain elusive and demand better characterization.

Augmentative effect of spinosin on pentobarbital-induced loss of righting reflex in mice associated with presynaptic 5-HT1A receptor.

Objectives: This study investigated whether spinosin potentiates pentobarbital-induced loss of righting reflex (LORR) in mice via 5-HT(1A) receptors.

Methods: Our primary endpoint for sedation was LORR. In addition, the basal rectal temperature was measured.

Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: the TMN and VLPO as key elements in the pathway.

To investigate the mechanism by which L-type Ca+ channel blockers exerted potentiating effects on pentobarbital-induced hypnosis, the present study was undertaken to determine if the interaction of diltiazem and serotonergic system influences the architecture of pentobarbital sleep in rats and examined c-Fos expression in the ventrolateral preoptic nucleus (VLPO) and the tuberomammillary nucleus (TMN). The polysomnogram consisting of EEG and EMG was recorded for analyzing sleep architecture. The results showed that diltiazem (2.

Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system.

Semen Zizhiphi Spinozae has been used extensively for the treatment of insomnia. This study investigated the effect and possible mechanism of action of spinosin (also known as 2''-beta-o-glucopyranosyl swertisin), a major constituent of semen Zizhiphi Spinozae, on sleep in mice. The present results showed that spinosin significantly and dose-dependently augmented pentobarbital (45 mg/kg, i.