T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data.

Transcriptome analysis has become increasingly utilized in aging research. However, the identification of the key molecular changes underlying aging processes and longevity-promoting regimens from transcriptome data remains challenging. Here, we present Transcriptomic CLassification via Adaptive learning of Signature States (T-CLASS), an online tool that identifies, from transcriptome data, gene sets of several hundred genes that provide an optimal representation of longevity and aging paradigms.

Inhibitory action of citronellol on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in juvenile mice.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) serves as the primary relay point for orofacial nociceptive inputs transmitted thin myelinated Aδ and unmyelinated C primary afferent fibers. Citronellol is a monoterpenoid alcohol found in the essential oil of various medicinal plants, such as . It has been shown to be able to alleviate orofacial pain.

Potential anti-nociceptive effect of beta-ionone on orofacial pain through GABA and glycine mimetic action on substantia gelatinosa neurons of trigeminal subnucleus caudalis in mice.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) plays a crucial role in integrating and regulating nociceptive inputs related to orofacial region. Although beta-ionone has been identified for its biomedical properties, its nociceptive effect was not fully studied. This study employed a whole-cell patch-clamp technique in juvenile mice to investigate the direct membrane effects of beta-ionone on SG neurons of the Vc.

Fucoxanthin Inhibits the NMDA and AMPA Receptors Through Regulating the Calcium Response on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice.

Glutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson's disease (PD), Alzheimer's disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial nociceptive transmission via Aδ and C primary afferent fibers, majorly utilize glutamate as the principal excitatory neurotransmitter. Fucoxanthin (FCX), a carotenoid pigment extracted from brown seaweed, possesses various pharmaceutical properties including neuroprotective effect in multiple neuronal populations.

OASIS portable: User-friendly offline suite for secure survival analysis.

Online application for survival analysis (OASIS) and its update, OASIS 2, have been widely used for survival analysis in biological and medical sciences. Here, we provide a portable version of OASIS, an all-in-one offline suite, to facilitate secure survival analysis without uploading the data to online servers. OASIS portable provides a virtualized and isolated instance of the OASIS 2 webserver, operating on the users' personal computers, and enables user-friendly survival analysis without internet connection and security issues.

Tissue-specific and tissue-agnostic effects of genome sequence variation modulating blood pressure.

Genome-wide association studies (GWASs) have identified numerous variants associated with polygenic traits and diseases. However, with few exceptions, a mechanistic understanding of which variants affect which genes in which tissues to modulate trait variation is lacking. Here, we present genomic analyses to explain trait heritability of blood pressure (BP) through the genetics of transcriptional regulation using GWASs, multiomics data from different tissues, and machine learning approaches.

Inhibitory Effects of Honokiol on Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Juvenile Mice.

Inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are known to be abundant in the substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc). Thus, it has been recognized as an initial synaptic site for regulating orofacial nociceptive stimuli. Honokiol, a principal active ingredient derived from the bark of Magnolia officinalis, has been exploited in traditional remedies with multiple biological effects, including anti-nociception on humans.

Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs.

Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5371 GLOM and 9787 TUBE genes with at least one variant significantly associated with expression (eGene) by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an "integrative prior" for Bayesian statistical fine-mapping.

Suppression of neurotransmission on gonadotropin-releasing hormone neurons in letrozole-induced polycystic ovary syndrome: A mouse model.

Objective: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder in reproductive-age women, characterized by the accretion of small cystic follicles in the ovary associated with chronic anovulation and overproduction of androgens. Ovarian function in all mammals is controlled by gonadotropin-releasing hormone (GnRH) neurons, which are the central regulator of the hypothalamic-pituitary-gonadal (HPG) axis. However, the impact on the neurotransmitter system regulating GnRH neuronal function in the letrozole-induced PCOS mouse model remains unclear.

Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model.

Chromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we developed a sequence-based machine learning method to evaluate and refine chromatin accessibility data.

Hydrogen peroxide suppresses excitability of gonadotropin-releasing hormone neurons in adult mouse.

It has been reported that reactive oxygen species (ROS) derived from oxygen molecule reduction can interfere with the cross-talk between the hypothalamic-pituitary-gonadal (HPG) axis and other endocrine axes, thus affecting fertility. Furthermore, ROS have been linked to GnRH receptor signaling in gonadotropes involved in gonadotropin release. There has been evidence that ROS can interfere with the HPG axis and gonadotropin release at various levels.

Deconvolution of bulk tumors into distinct immune cell states predicts colorectal cancer recurrence.

Predicting colorectal cancer recurrence after tumor resection is crucial because it promotes the administration of proper subsequent treatment or management to improve the clinical outcomes of patients. Several clinical or molecular factors, including tumor stage, metastasis, and microsatellite instability status, have been used to assess the risk of recurrence, although their predictive ability is limited. Here, we predicted colorectal cancer recurrence based on cellular deconvolution of bulk tumors into two distinct immune cell states: cancer-associated (tumor-infiltrating immune cell-like) and noncancer-associated (peripheral blood mononuclear cell-like).

Evolutionary rewiring of regulatory networks contributes to phenotypic differences between human and mouse orthologous genes.

Mouse models have been engineered to reveal the biological mechanisms of human diseases based on an assumption. The assumption is that orthologous genes underlie conserved phenotypes across species. However, genetically modified mouse orthologs of human genes do not often recapitulate human disease phenotypes which might be due to the molecular evolution of phenotypic differences across species from the time of the last common ancestor.

Resveratrol activates GABA and/or glycine receptors on substantia gelatinosa neurons of the subnucleus caudalis in mice.

Although a number of studies have reported that resveratrol has analgesic effects, the direct effect of resveratrol on substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) involved in orofacial nociceptive transmission has not been clearly examined. Thus, the objective of this study was to investigate effects of resveratrol on SG neurons of Vc in mice using a whole-cell patch-clamp technique. Resveratrol (500 μM) induced repeatable inward currents without desensitisation.

MON-2, a Golgi protein, mediates autophagy-dependent longevity in .

The Golgi apparatus plays a central role in trafficking cargoes such as proteins and lipids. Defects in the Golgi apparatus lead to various diseases, but its role in organismal longevity is largely unknown. Using a quantitative proteomic approach, we found that a Golgi protein, MON-2, was up-regulated in long-lived mutants with mitochondrial respiration defects and was required for their longevity.

GABA- and Glycine-Mimetic Responses of Linalool on the Substantia Gelatinosa of the Trigeminal Subnucleus Caudalis in Juvenile Mice: Pain Management through Linalool-Mediated Inhibitory Neurotransmission.

Linalool, a major odorous constituent in essential oils extracted from lavender, is known to have a wide range of physiological effects on humans including pain management. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is involved in transmission of orofacial nociceptive responses through thin myelinated A[Formula: see text] and unmyelinated C primary afferent fibers. Up to date, the orofacial antinociceptive mechanism of linalool concerning SG neurons of the Vc has not been completely clarified yet.

Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons.

Lithium (Li) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities.

Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats.

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models.

Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients.

Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we present a machine-learning framework to identify robust drug biomarkers by taking advantage of network-based analyses using pharmacogenomic data derived from three-dimensional organoid culture models.

Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells.

Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles.

Inhibitory actions of borneol on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is the first relay site for the orofacial nociceptive inputs the thin myelinated Aδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonored herbal ingredients in traditional Chinese medicine, is a popular treatment for anxiety, anesthesia, and antinociception. However, to date, little is known as to how borneol acts on the SG neurons of the Vc.

Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice.

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic-pituitary-gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear.

Potentiation of the Glycine Response by Bisphenol A, an Endocrine Disrupter, on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice.

Lamina II, also called the substantia gelatinosa (SG) of the medullary dorsal horn (the trigeminal subnucleus caudalis, Vc), is thought to play an essential role in the control of orofacial nociception because it receives the nociceptive signals from primary afferents, including thin myelinated Aδ- and unmyelinated C-fibers. Glycine, the main inhibitory neurotransmitter in the central nervous system, plays an essential role in the transference of nociceptive messages from the periphery to higher brain regions. Bisphenol A (BPA) is reported to alter the morphological and functional characteristics of neuronal cells and to be an effector of a great number of ion channels in the central nervous system.