SREBP-Dependent Regulation of Lipid Homeostasis Is Required for Progression and Growth of Pancreatic Ductal Adenocarcinoma.

Unlabelled: Solid tumors undergo metabolic reprogramming when growth outstrips local nutrient supply. Lipids such as cholesterol and fatty acids are required for continued tumor cell proliferation, and oncogenic mutations stimulate de novo lipogenesis to support tumor growth. Sterol regulatory element-binding protein (SREBP) transcription factors control lipid homeostasis by activating genes required for lipid synthesis and uptake.

A High-Throughput Screening Platform Identifies FDA-Approved Drugs That Inhibit SREBP Pathway Activation.

Sterol regulatory element-binding protein (SREBP) transcription factors are central regulators of lipid homeostasis and are essential for lipid metabolic reprogramming that supports tumor growth in multiple cancers. SREBP pathway inhibitors have been identified, but bioavailable compounds are lacking. To address this need, we designed a novel approach for screening a collection of 4,474 FDA-approved drugs.

In vivo CRISPR screening identifies geranylgeranyl diphosphate as a pancreatic cancer tumor growth dependency.

Objective: Cancer cells must maintain lipid supplies for their proliferation and do so by upregulating lipogenic gene programs. The sterol regulatory element-binding proteins (SREBPs) act as modulators of lipid homeostasis by acting as transcriptional activators of genes required for fatty acid and cholesterol synthesis and uptake. SREBPs have been recognized as chemotherapeutic targets in multiple cancers, however it is not well understood which SREBP target genes are essential for tumorigenesis.

In vivo CRISPR screening identifies geranylgeranyl diphosphate as a pancreatic cancer tumor growth dependency.

Cancer cells must maintain lipid supplies for their proliferation and do so by upregulating lipogenic gene programs. The sterol regulatory element-binding proteins (SREBPs) act as modulators of lipid homeostasis by acting as transcriptional activators of genes required for fatty acid and cholesterol synthesis and uptake. SREBPs have been recognized as chemotherapeutic targets in multiple cancers, however it is not well understood which SREBP target genes are essential for tumorigenesis.

[Validation of Quantitative Accuracy and Variability in Lu Imaging Using Monte Carlo Simulation].

Purpose: To predict side effects and optimize injection doses in the dosimetry of Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for Lu imaging under various imaging conditions.

Methods: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.

SREBP-dependent regulation of lipid homeostasis is required for progression and growth of pancreatic ductal adenocarcinoma.

Unlabelled: Metabolic reprogramming is a necessary component of oncogenesis and cancer progression that solid tumors undergo when their growth outstrips local nutrient supply. The supply of lipids such as cholesterol and fatty acids is required for continued tumor cell proliferation, and oncogenic mutations stimulate de novo lipogenesis to support tumor growth. Sterol regulatory element-binding protein (SREBP) transcription factors control cellular lipid homeostasis by activating genes required for lipid synthesis and uptake.

Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners.

The receptor protein tyrosine phosphatase phogrin primarily localizes to hormone secretory granules in neuroendocrine cells. Concurrent with glucose-stimulated insulin secretion, phogrin translocates to pancreatic β-cell plasma membranes, where it interacts with insulin receptors (IRs) to stabilize insulin receptor substrate 2 (IRS2) that, in turn, contributes to glucose-responsive β-cell growth. Pancreatic β-cell development was not altered in β-cell-specific, phogrin-deficient mice, but the thymidine incorporation rate decreased in phogrin-deficient islets with a moderate reduction in IRS2 protein expression.

Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene.

We recently reported that phogrin, also known as IA-2β or PTPRN2, forms a complex with the insulin receptor in pancreatic β cells upon glucose stimulation and stabilizes insulin receptor substrate 2. In β cells of systemic phogrin gene knockout (IA-2β) mice, impaired glucose-induced insulin secretion, decreased insulin granule density, and an increase in the number and size of lysosomes have been reported. Since phogrin is expressed not only in β cells but also in various neuroendocrine cells, the precise impact of phogrin expressed in β cells on these cells remains unclear.

Association between Masticatory Performance, Nutritional Intake, and Frailty in Japanese Older Adults.

The older adult population in Japan is expected to increase. Therefore, long-term care and frailty prevention are important. However, the relationship between masticatory performance, nutritional intake, and frailty remains unclear.

Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study.

Aim: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project.

Methods: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e.

Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan.

Background: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs.

Methods: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan.

The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the "Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)" project.

Background: Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

Introduction: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS).

Methods: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study.

Satisfaction with web-based courses on clinical practice guidelines for psychiatrists: Findings from the "Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)" project.

To disseminate, educate, and validate psychiatric clinical practice guidelines, the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project was launched in 2016. In this study, we investigated whether the web-based courses offered by this project would be as effective as the face-to-face courses. We analyzed and compared survey answers about overall participant satisfaction with the course and answers regarding clinical knowledge of schizophrenia and major depressive disorder between 170 participants who took the web-based courses in 2020 and 689 participants who took the face-to-face courses from 2016 to 2019.

Development of an individual fitness score (IFS) based on the depression treatment guidelines of in the Japanese Society of Mood Disorders.

Aim: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders.

Factors related to masticatory performance in junior and senior high school students and young adults: A cross-sectional study.

Purpose: Maintaining good masticatory function from a young age promotes lifelong health, yet limited studies have explored masticatory performance in young individuals. We investigated the relationship of sex, age, and individual oral functions with masticatory performance among junior and senior high school students and young adults.

Methods: This cross-sectional study included students aged 12-13, 14-15, and 16-17 years (groups S1, S2, and S3, respectively) and young adults aged 20-40 years (group YA).

Development of individual fitness score for conformity of prescriptions to the "Guidelines For Pharmacological Therapy of Schizophrenia".

Aims: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence-practice-gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'.

[Effects of Skin Environmental Changes by Steam Towel, Ethanol, l-Menthol and Carpronium on the Drug Behavior in the Minoxidil Nanoparticles-applied Mice].

We previously designed the formulation containing minoxidil (MXD) nanoparticles (MXD-NPs), and found that the MXD-NPs can mainly deliver MXD into hair bulbs via hair follicles pathway, and that the therapeutic efficiency for hair growth is higher in comparison with the formulation containing dissolved MXD. In this study, we investigated whether the skin environmental changes by the treatment of steam towel, ethanol, l-menthol and commercially available (CA) carpronium affect the drug behavior in the MXD-NPs-applied mice. The steam towel, ethanol, l-menthol and CA-carpronium were pre-treated 3 min before MXD-NPs application, and the MXD content in the hair bulge, bulb, skin tissue and blood of mice were measured 4 h after MXD-NPs application.

Effect of Self- and Inter-Cultivar Grafting on Growth and Nutrient Content in Sweet Basil ( L.).

Vegetable grafting has been applied to fruiting crops, yet only to a limited extent in leafy greens and herbs which may also benefit from grafting. In this study, we examined the effect of reciprocal grafting two sweet basil ( L.) cultivars of differing vigor on plant growth and leaf mineral nutrient concentration to test whether differences in growth exist due to grafting and whether such differences are due to altered plant nutrient status in two trials.

Characteristics of the treatments for each severity of major depressive disorder: A real-world multi-site study.

Purpose: In the treatment guidelines for major depressive disorder (MDD), the recommended treatment differs based on the severity. However, the type of treatment provided based on the severity of MDD in real-world clinical practice has not been investigated. In this study, we clarified the actual situation of MDD treatment in clinical practice and compared the treatment based on the severity of MDD.

Prescription of Anticholinergic Drugs in Patients With Schizophrenia: Analysis of Antipsychotic Prescription Patterns and Hospital Characteristics.

In several clinical guidelines for schizophrenia, long-term use of anticholinergic drugs is not recommended. We investigated the characteristics of the use of anticholinergics in patients with schizophrenia by considering psychotropic prescription patterns and differences among hospitals. A cross-sectional, retrospective prescription survey at the time of discharge was conducted on 2027 patients with schizophrenia from 69 Japanese hospitals.

2,2,6,6-Tetramethylpiperidine-1-oxyl acts as a volatile inhibitor of ferroptosis and neurological injury.

Ferroptosis, a type of oxidative stress cell death, has been implicated in cell injury in several diseases, and treatments with specific inhibitors have been shown to protect cells and tissues. Here we demonstrated that a treatment with the nitroxide radical, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), prevented the ferroptotic cell death in an airborne manner. Other TEMPO derivatives and lipophilic antioxidants, such as Trolox and ferrostatin-1, also prevented cell death induced by erastin and RSL3; however, only TEMPO exhibited inhibitory activity from a physically distant location.