Loss of Angulin-1/LSR promotes vasculogenic mimicry and epithelial-mesenchymal transition in breast cancer.

Vasculogenic mimicry (VM) is a process by which tumor cells form vessel-like network to secure oxygen and nutrients essential for tumor growth. Intercellular junctions, including tight junctions, may play a critical role in this process, important for VM. Here, we investigated the role of angulin-1/LSR (Ang-1), a key component of tricellular tight junctions, in VM regulation.

Colonizing bacteria around aggregated lymphoid tissue of the rat ascending colon change diurnally and affect the host local transcriptome.

The settlement levels of indigenous bacteria show circadian rhythms in various regions of the rat alimentary tract. Numerous bacteria colonize between the mucosal folds of the ascending colon in rodents; however, the rhythm of bacteria colonizing the ascending colon remains to be clarified. Therefore, we first aimed to examine the diurnal changes in bacteria colonizing in the rat ascending colon.

A Case Report of Graves' Disease Diagnosed during an Evaluation of an Abnormal Opacity on a Chest X-ray with a Review of The Pertinent Literature.

We treated a 43-year-old woman with Graves' disease (GD), complicated by thymic hyperplasia. Routine chest radiography revealed an abnormal opacity, and computed tomography revealed an anterior mediastinal tumor. At the initial visit to our institution, blood tests revealed hyperthyroidism with positive thyroid-stimulating hormone receptor antibodies, confirming the diagnosis of GD.

ACLY inhibition promotes tumour immunity and suppresses liver cancer.

Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC). Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation.

PTBP1 Depletion in Mature Astrocytes Reveals Distinct Splicing Alterations Without Neuronal Features.

Astrocyte-to-neuron reprogramming via depletion of PTBP1, a potent repressor of neuronal splicing, has been proposed as a therapeutic strategy, but its efficacy remains debated. While some reported successful conversion, others disputed this, citing a lack of neuronal gene expression as evidence of failed reprogramming. This interpretation was further challenged, attributed to incomplete PTBP1 inactivation, fueling ongoing controversy.

Benefits and Accuracy of Real-Time CGM in Children and Adolescents with Type 1 Diabetes Attending Summer Camp: 2nd year.

Context: In 2023, we employed Dexcom G6 for real-time continuous glucose monitoring (rt-CGM); it showed high usefulness but unsatisfactory accuracy in type 1 diabetes summer camp (camp) participants.

Objective: To assess the usefulness, recommendation and accuracy of a new rt-CGM system in camp, 2024.

Methods: Sensor glucose (SG) concentrations were measured by Dexcom G7 (G7) from 6 days prior to camp.

Age-Related Glucose Intolerance Is Associated with Impaired Insulin Secretion in Community-Dwelling Japanese Adults: The Kumamoto Koshi Study.

: Glucose tolerance progressively declines with age. However, the effects of aging on insulin secretion and insulin sensitivity in Japanese subjects are unclear. : We conducted an oral glucose tolerance test (OGTT) in residents aged between 22 and 85 years in Koshi City, Kumamoto Prefecture, Japan, to clarify the characteristics of insulin secretion and insulin sensitivity in older adults.

Shiba: a versatile computational method for systematic identification of differential RNA splicing across platforms.

Alternative pre-mRNA splicing (AS) is a fundamental regulatory process that generates transcript diversity and cell type variation. We developed Shiba, a comprehensive method that integrates transcript assembly, splicing event identification, read counting, and differential splicing analysis across RNA-seq platforms. Shiba excels in capturing annotated and unannotated AS events with superior accuracy, sensitivity, and reproducibility.

Orally administrated acetate inhibits atherosclerosis progression through AMPK activation via GPR43 in plaque macrophages.

Background And Aims: Oral administration of acetic acid, a short-chain fatty acid, has been shown to efficiently reduce obesity and insulin resistance in both experimental animals and humans. The anti-atherosclerotic effect of acetate is expected owing to its anti-inflammatory and anti-oxidative stress characteristics; however, this remains to be fully understood.

Methods: For 12 weeks, apolipoprotein E-deficient mice were administered 0.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma.

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.

Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).

[Obesity, Metabolic Syndrome, and Fatty Liver Disease].

Obesity, metabolic syndrome, and fatty liver disease, particularly nonalcoholic fatty liver disease(NAFLD), are significant health issues in current society. These conditions are linked to lifestyle changes such as overeating and lack of exercise, and their prevalence is increasing. Obesity is defined using body mass index(BMI), with a BMI of 25 kg/m or higher considered obese in Japan due to the higher health risks in this population.

Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression.

Lipodystrophy and obesity are associated with insulin resistance and metabolic syndrome accompanied by fat tissue dysregulation. Here, we show that serine protease inhibitor A1 (SerpinA1) expression in the liver is increased during recovery from lipodystrophy caused by the adipocyte-specific loss of insulin signaling in mice. SerpinA1 induces the proliferation of white and brown preadipocytes and increases the expression of uncoupling protein 1 (UCP1) to promote mitochondrial activation in mature white and brown adipocytes.

Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.

Background & Aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.

Female sex hormones inversely regulate acute kidney disease susceptibility throughout life.

While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules.

The benefits and accuracy of real-time continuous glucose monitoring in children and adolescents with type 1 diabetes attending a summer camp.

Aims/introduction: This study evaluated the usability, satisfaction, and accuracy of a real-time continuous glucose monitoring (rt-CGM) in children and adolescents with type 1 diabetes (T1D) attending a summer camp.

Materials And Methods: Seven children and adolescents with T1D (camper) and 31 of healthcare providers (HCPs) participating in a 2-day summer camp in Kumamoto, Japan were enrolled. The usability and satisfaction were evaluated by tailored questionnaire.

Ultra-processed foods cause weight gain and increased energy intake associated with reduced chewing frequency: A randomized, open-label, crossover study.

Aim: To elucidate the effects of ultra-processed foods (UPFs) on body weight and ad libitum energy intake compared with non-UPFs.

Materials And Methods: In this randomized, open-label crossover study conducted at the University of Tokyo Hospital, overweight/obese Japanese male participants were randomly assigned (1:1) to start the study with consumption of either UPFs or non-UPFs for 1 week, followed by a 2-week washout period, before crossing over to the alternate food diet for 1 week. Individuals with diabetes, hypertension or any other medical conditions who visited a hospital regularly were excluded.

Physiological and pathophysiological actions of insulin in the liver.

The liver plays an important role in the control of glucose homeostasis. When insulin levels are low, such as in the fasting state, gluconeogenesis and glycogenolysis are stimulated to maintain the blood glucose levels. Conversely, in the presence of increased insulin levels, such as after a meal, synthesis of glycogen and lipid occurs to maintain the blood glucose levels within normal range.

Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy.

Background And Aims: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration-approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC.

Organelle communication maintains mitochondrial and endosomal homeostasis during podocyte lipotoxicity.

Organelle stress exacerbates podocyte injury, contributing to perturbed lipid metabolism. Simultaneous organelle stresses can occur in the kidney in the diseased state; therefore, a thorough analysis of organelle communication is crucial for understanding the progression of kidney diseases. Although organelles closely interact with one another at membrane contact sites, limited studies have explored their involvement in kidney homeostasis.

The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown.