NAD deficiency plays essential roles in the hyperuricemia of stroke-prone spontaneously hypertensive rat via xanthine dehydrogenase to xanthine oxidase conversion.

Inhibition of xanthine oxidoreductase (XOR) was shown to ameliorate the stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), suggesting hyperuricemia had a pathological role in this rat model. In this study, we thus aimed to explore mechanisms inducing hyperuricemia in SHRSP. XOR is known to have two forms, xanthine dehydrogenase (XDH) as the prototype and xanthine oxidase (XO) as the converted form through cleavage of a peptide bond or through formation of disulfide bonds in the enzyme.

Left ventricular size and heart failure: A cardiac MRI assessment of 38,129 individuals from the UK Biobank.

Background: Previous studies suggest that prevalent heart failure (HF) differs based on left ventricular ejection fraction (LVEF) and left ventricular (LV) chamber size. Furthermore, the prevalence of HF with preserved ejection fraction (HFpEF) is often considered approaching, or exceeding that of HF with reduced ejection fraction in the community.

Aim: The aim of this study was to evaluate prevalent and incident HF based on LVEF and CMR-determined LV size within a large community-dwelling cohort.

Use of Polygenic Risk Score for Prediction of Heart Failure in Cancer Survivors.

Background: The risk for heart failure (HF) is increased among cancer survivors, but predicting individual HF risk is difficult. Polygenic risk scores (PRS) for HF prediction summarize the combined effects of multiple genetic variants specific to the individual.

Objectives: The aim of this study was to compare clinical HF prediction models with PRS in both cancer and noncancer populations.

An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1.

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm.

Relief of pain in mice by an antibody with high affinity for cell adhesion molecule 1 on nerves.

Aims: Cell adhesion molecule 1 (CADM1) is a member of the immunoglobulin superfamily and is abundantly expressed on nerve fibers. Recently, the anti-CADM1 ectodomain antibody 3E1 has proven useful as a drug delivery vector for CADM1-expressing cells in vitro. When injected subcutaneously into mice, whether 3E1 accumulates on nerve fibers and serves as an analgesic was examined.

HLA Association among Thai Patients with Diffuse and Limited Cutaneous Systemic Sclerosis.

This study aimed to clarify the association of HLA Class I and II with dcSSc and lcSSc in Thais. HLA typing for 11 gene loci (Class I: HLA-A, B and C, and Class II [HLA-DR, DP and DQ]) was carried out using the Next Generation DNA Sequencing method (three fields) in 92 Thai patients with systemic sclerosis (55 dcSSc, 37 lcSSc) and 135 healthy controls (HCs). The distribution of HLA alleles in patients with dcSSc and lcSSc was compared.

Efficient intracellular drug delivery by co-administration of two antibodies against cell adhesion molecule 1.

Cell adhesion molecule 1 (CADM1), a single-pass transmembrane protein, is involved in oncogenesis. We previously demonstrated the therapeutic efficacy of anti-CADM1 ectodomain monoclonal antibodies against mesothelioma; however, the underlying mechanism is unclear. In the present study, we explored the molecular behavior of anti-CADM1 antibodies in CADM1-expressing tumor cells.

Immediate Breast Reconstruction With Latissimus Dorsi Myocutaneous Flap and Silicone Implant Followed by Adjuvant Radiotherapy for Breast Cancer.

Background: About 30% to 50% of women with breast cancer undergo mastectomy, and approximately 50% of them will receive adjuvant radiotherapy (ART). This study evaluates the medium- and long-term impact of ART after immediate breast reconstruction (IBR) with latissimus dorsi myocutaneous (LDM) flap and silicone implants.

Methods: Clinical, surgical, and oncological data were retrospectively collected and analyzed based on the medical records of 176 patients who had undergone IBR with LDM flap and silicone implants.

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction.

Blood cell phenotypes are routinely tested in healthcare to inform clinical decisions. Genetic variants influencing mean blood cell phenotypes have been used to understand disease aetiology and improve prediction; however, additional information may be captured by genetic effects on observed variance. Here, we mapped variance quantitative trait loci (vQTL), i.

Ploidy inference from single-cell data: application to human and mouse cell atlases.

Ploidy is relevant to numerous biological phenomena, including development, metabolism, and tissue regeneration. Single-cell RNA-seq and other omics studies are revolutionizing our understanding of biology, yet they have largely overlooked ploidy. This is likely due to the additional assay step required for ploidy measurement.

Is Immediate Breast Reconstruction With a Latissimus Dorsi Myocutaneous Flap Safe for Starting Adjuvant Chemotherapy in Patients With Breast Cancer?

Introduction: Immediate breast reconstruction following mastectomy reduces perceptions of mutilation and femininity issues in oncological patients, but surgical complications should not delay chemotherapy. This study evaluated postsurgical complications in patients who underwent radical breast surgery followed by immediate reconstruction with latissimus dorsi myocutaneous flaps and silicone implants, along with resulting impacts in delaying chemotherapy.

Materials And Methods: This retrospective study utilized a prospectively maintained database.

Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks.

Aims: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown.

Sodium L-Aspartate Supplementation Improves Repeated-Sprint Performance.

Aspartate supplementation has been reported to improve endurance performance by facilitating the tricarboxylic acid cycle flux. The present study was performed to investigate the effects of aspartate supplementation on repeated-sprint performance and blood pH. Following an overnight fast, fourteen healthy males completed three sets of 10 × 6 s maximal sprints after consuming sodium L-aspartate (ASP) or placebo (PLA), in a double-blind manner.

Potential Contribution of Cell Adhesion Molecule 1 to the Binding of SARS-CoV-2 Spike Protein to Mouse Nasal Mucosa.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first infects the host nasal mucosa, where the viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) on the mucosal cells. This study aimed at searching host cell surface molecules that could contribute to the infection in two views; abundance on host cells and affinity to the spike protein. Since the nasal mucosa is lined by respiratory and olfactory epithelia, and both express an immunoglobulin superfamily member cell adhesion molecule 1 (CADM1), whether CADM1 would participate in the spike protein binding was examined.

Neoadjuvant chemotherapy impact on outcomes in immediate breast reconstruction with latissimus dorsi flap and silicone implant.

Background And Objectives: Neoadjuvant chemotherapy (NCH) has demonstrated efficacy in downsizing tumors and facilitating less extensive surgery. However, immediate breast reconstruction (IBR) after NCH has raised concerns regarding higher complication rates. This study evaluates the impact of NCH on outcomes following IBR with a latissimus dorsi flap and implant (LDI) after mastectomy.

Genotypes of Stim1 and the proximal region on chromosome 1 exert opposite effects on stroke susceptibility in stroke-prone spontaneously hypertensive rat.

Background: The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetic model for cerebral stroke. Although a recent study on a congenic SHRSP suggested that a nonsense mutation in stromal interaction molecule 1 ( Stim1 ) encoding a major component of store-operated Ca 2+ entry was a causal variant for stroke in SHRSP, this was not conclusive because the congenic region including Stim1 in that rat was too wide. On the other hand, we demonstrated that the Wistar-Kyoto (WKY)-derived congenic fragment adjacent to Stim1 exacerbated stroke susceptibility in a congenic SHRSP called SPwch1.

Deciphering the genetic landscape of obesity: a data-driven approach to identifying plausible causal genes and therapeutic targets.

Objectives: Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. However, identifying the causal genes, pathways, and tissues/cell types responsible for these associations remains a challenge, and standardized analysis workflows are lacking. Additionally, due to limited treatment options for obesity, there is a need for the development of new pharmacological therapies.

Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq.

We investigated the progression of nonalcoholic fatty liver disease from fatty liver to steatohepatitis using single-nucleus and bulk ATAC-seq on the livers of rats fed a high-fat diet (HFD). Rats fed HFD for 4 wk developed fatty liver, and those fed HFD for 8 wk further progressed to steatohepatitis. We observed an increase in the proportion of inflammatory macrophages, consistent with the pathological progression.

Case report: Evolution of catatonic mutism and psychotic symptoms in an adolescent with Down syndrome: transition from Down syndrome disintegrative disorder to anti-N-methyl-D-aspartate receptor encephalitis.

During her first year of junior high school, a 12-year-old Japanese girl with Down syndrome experienced dizziness, gait disruption, paroxysmal weakness in her hands, and sluggish speaking. Regular blood tests and a brain MRI revealed no abnormalities, and she was tentatively diagnosed with adjustment disorder. Nine months later, the patient experienced a subacute sickness of chest pain, nausea, sleep problem with night terrors, and delusion of observation.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Interstrand crosslinking oligonucleotides elucidate the effect of metal ions on the methylation status of repetitive DNA elements.

DNA methylation plays an important physiological function in cells, and environmental changes result in fluctuations in DNA methylation levels. Metal ions have become both environmental and health concerns, as they have the potential to disrupt the genomic DNA methylation status, even on specific sequences. In the current research, the methylation status of two typical repetitive DNA elements, i.