Benzbromarone Analog SAR: Potent hURAT1 (SLC22A12) Inhibitors and Drug Transporter Interaction Studies.

Purpose: There were two main purposes for this study. One, to report two benzbromarone analogs and test their in vitro activity in the URAT1 inhibition assay; and two, to probe the structure-activity relationship (SAR) of various benzbromarone analogs regarding other drug transporters that may play a role in the uric acid uptake/elimination interplay.

Methods: In brief, chemical synthesis of two benzbromarone analogs was prepared using methods analogous to those reported.

Subdiaphragmatic vagotomy reduces hypothalamic oxytocin expression and blood levels after oral MDMA administration in male rats.

3,4-Methylenedioxymethamphetamine (MDMA) is a widely recognized entactogen frequently used recreationally. It is known for its interaction with the serotonin and oxytocin systems, which underlie its entactogenic effects in humans. Recently, we demonstrated that the gut-brain axis, mediated by the subdiaphragmatic vagus nerve, contributes to MDMA-induced resilience enhancement in rodents.

Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice.

Arketamine, the (R)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.

Examining the content validity of the Comprehensive Assessment of Functioning for Mental Illness-Subjective Version (CAMI-S) with reference to the framework of the International Classification of Functioning, Disability, and Health (ICF).

Aim: To support the achievement of life goals and social participation of persons with mental illness, based on the World Health Organization's International Classification of Functioning, Disability, and Health (ICF), we generated items, identified domains, and examined the content validity of the Comprehensive Assessment of Functioning for Mental Illness-Subjective Version (CAMI-S). The purpose was to assess patients' strengths and weaknesses by incorporating the patient and public involvement perspective.

Methods: Focus group interviews on the items to be included were conducted with Group A.

The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients.

Background: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab.

Objective: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment.

Preconditioning-Induced Facilitation of Lactate Release from Astrocytes Is Essential for Brain Ischemic Tolerance.

A sublethal ischemic episode [termed preconditioning (PC)] protects neurons in the brain against a subsequent severe ischemic injury. This phenomenon is known as brain ischemic tolerance and has received much attention from researchers because of its robust neuroprotective effects. We have previously reported that PC activates astrocytes and subsequently upregulates P2X7 receptors, thereby leading to ischemic tolerance.

Cryo-EM structure of P-glycoprotein bound to triple elacridar inhibitor molecules.

P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. This mechanism is particularly problematic in cancer cells, where it diminishes the therapeutic efficacy of anticancer drugs. P-gp inhibitors, such as elacridar, have been developed to circumvent the decrease in drug efficacy due to P-gp efflux.

Post-Disaster Community Transition of Psychiatric Inpatients: Lessons from the Fukushima Nuclear Accident.

This study sought to explore factors related to community transition after the mandatory evacuation of psychiatric inpatients to other hospitals owing to the Fukushima Daiichi Nuclear Power Plant accident. A retrospective cohort design was adopted and 391 psychiatric patients were examined. Univariate and multivariate analyses were conducted to confirm the association between the achievement or non-achievement of discharge to community living and their backgrounds (age, gender, evacuation destination, psychiatric diagnoses, and physical complications).

Copy Number Gain in Androgen Receptors Predicts the Poor Prognosis in Japanese Castration-resistant Prostate Cancer.

Background/aim: The prognostic significance of androgen receptor amplification (AR amp) in cell-free DNA (cfDNA) was studied in Japanese patients with castration-resistant prostate cancer (CRPC).

Patients And Methods: A total of 120 serum samples were obtained from 38 patients with CRPC. Serum cfDNA was purified and the AR copy number was determined.

Central administered xenin induced Fos expression in nesfatin-1 neurons in rats.

Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system.

Dysuricemia-A New Concept Encompassing Hyperuricemia and Hypouricemia.

The importance of uric acid, the final metabolite of purines excreted by the kidneys and intestines, was not previously recognized, except for its role in forming crystals in the joints and causing gout. However, recent evidence implies that uric acid is not a biologically inactive substance and may exert a wide range of effects, including antioxidant, neurostimulatory, proinflammatory, and innate immune activities. Notably, uric acid has two contradictory properties: antioxidant and oxidative ones.

Medical School Clinical Trials Educational Intervention: Impact on Knowledge and Attitudes.

Medical student knowledge and opinions of clinical research have important ramifications for how likely they will be to refer patients into clinical trials as practicing physicians. This study examined students understanding, knowledge, and attitudes about clinical trials at the start of medical school and after completion of a multi-faceted intervention designed to increase medical students' confidence in understanding and explaining clinical trials during the pre-clinical and clinical years. Medical students were surveyed about their knowledge of and attitudes toward clinical trials in their first (N = 724) and third (N = 191) years of medical school.

Machine-learning predicts time-series prognosis factors in metastatic prostate cancer patients treated with androgen deprivation therapy.

Machine learning technology is expected to support diagnosis and prognosis prediction in medicine. We used machine learning to construct a new prognostic prediction model for prostate cancer patients based on longitudinal data obtained from age at diagnosis, peripheral blood and urine tests of 340 prostate cancer patients. Random survival forest (RSF) and survival tree were used for machine learning.

Contribution of the L-Type Amino Acid Transporter Family in the Diagnosis and Treatment of Prostate Cancer.

The L-type amino acid transporter (LAT) family contains four members, LAT1~4, which are important amino acid transporters. They mainly transport specific amino acids through cell membranes, provide nutrients to cells, and are involved in a variety of metabolic pathways. They regulate the mTOR signaling pathway which has been found to be strongly linked to cancer in recent years.

Interaction of buspirone and its major metabolites with human organic cation transporters.

Buspirone, a cationic drug, is an anxiolytic and antidepressant drug. However, whether buspirone and its metabolites are interacted with organic cationic transporter remains uncertain. In this study, we examined the interaction of buspirone and its major metabolites 1-(2-pyrimidinyl)piperazine (1-PP) and 6-hydroxybuspirone (6'-OH-Bu) with hOCTs using human hepatocellular carcinoma (HepG2), human colorectal adenocarcinoma (Caco-2) cells, and S2 cells expressing OCT1 (S2hOCT1), 2 (S2hOCT2), or 3 (S2hOCT3).