Identification of Gallbladder-Specific Distal Regulatory Sequence of Murine Sox17.

Sox17 is a key transcriptional regulator of endoderm formation and function in the gallbladder, blood vessels and reproductive organs. Although multiple transcript variants of Sox17 have been suggested, the precise mechanisms underlying their time- and tissue-specific expression remain unclear. In this study, we discovered two putative regulatory sequences (R1 and R2) adjacent to different transcription start sites of mouse Sox17 exon 1 and generated deletion mice for these regions (Sox17).

Saving a hopeless tooth with a four-wall bone defect: A case report.

Background: Recombinant human fibroblast growth factor-2 (rhFGF-2) has been shown to effectively promote the formation of new periodontal tissues, and its efficacy has been demonstrated in clinical settings. Moreover, the clinical and radiographic outcomes in the treatment of periodontal infrabony defects can be improved by using rhFGF-2 in combination with a bone substitute. Here, we present a case of four-wall bone defect in a tooth treated by combination regenerative therapy using rhFGF-2 and beta-tricalcium phosphate (β-TCP).

Gearing Effects on -9-Anth-PyBidine-Cu(OAc)-Catalyzed Asymmetric Direct Haloimidation Reactions of Alkylidenemalononitriles.

A newly developed -9-anthranylmethyl bis(imidazolidine)pyridine (-9-Anth-PyBidine)-Cu(OAc) complex catalyzed asymmetric haloimidation reactions of alkylidenemalononitriles with -bromosuccinimide and -chlorosuccinimide, employing the succinimide moiety directly as a copper-bound nucleophile. The anthranyl substituent showed a gearing effect that produced a well-organized asymmetric sphere involving the -H proton of the imidazolidine ring in the ligand. The gearing effect afforded hydrogen bonding-assisted copper-catalyzed haloimidation reactions with high enantioselectivity.

Brain-derived neurotrophic factor promotes bone regeneration in a canine model of peri-implantitis.

Purpose: The present study aims to determine whether the brain-derived neurotrophic factor (BDNF)/high-molecular-weight hyaluronic acid (HMW-HA) complex could regenerate bone around implants lost due to peri-implantitis.

Methods: Dogs had their three premolars extracted, and three implants were placed on each side. After osseointegration, 3-0 silk threads were ligated around the healing abutment for 12 weeks.

Role of transglutaminase 2 in promoting biglycan synthesis in idiopathic gingival fibromatosis.

Background: This study aimed to elucidate the pathogenesis of idiopathic gingival fibromatosis (IGF).

Methods: Human gingival fibroblasts (hGFs) were isolated from patients with IGF and periodontitis. Differential gene expression in the hGFs was analyzed using RNA sequencing.

Genomic diversity of the Japanese wheat core collection and selection of alleles for agronomic traits in the breeding process.

Combining high-throughput genotyping data with the latest wheat genomic information provided more detailed information on the genetic diversity of the Japanese wheat core collection (JWC). Analysis of genomic population structure divided the JWC accessions into three populations: northeast Japan accessions, native and southwest Japan accessions, and modern accessions showing mixed breeding patterns. This indicates that Japanese wheat varieties have a background of native genomes from southwest Japan incorporating valuable genes from various exotic lines, which is supported by the history of Japanese wheat breeding.

The oral cavity is a potential reservoir of gram-negative antimicrobial-resistant bacteria, which are correlated with ageing and the number of teeth.

Objectives: The suppression of antimicrobial-resistant bacteria (ARB) is an important issue worldwide. In recent years, the presence of various ARB in the oral cavity has been reported, but the details remain unclear. Therefore, we aimed to isolate ARB from the oral cavity and investigate the factors affecting ARB colonization.

Patient preferences for advanced therapies in ulcerative colitis using conjoint analysis.

Background/aims: Selecting an optimal advanced therapy for ulcerative colitis (UC) is difficult because of the increasing number of available therapies. This study assessed UC patients' preferences for drug profiles in decision-making regarding advanced therapies using conjoint analysis.

Methods: A web-based survey was conducted from October to November 2023 in patients with UC aged ≥ 18 years with prior oral 5-aminosalicylic acid treatment (UMIN000052327).

Generation of insulin-like growth factor 1 receptor-knockout pigs as a potential system for interspecies organogenesis.

Background: To overcome organ shortage during transplantation, interspecies organ generation via blastocyst complementation has been proposed, although not yet in evolutionarily distant species. To establish high levels of chimerism, low chimerism is required early in development, followed by high chimerism, to effectively complement the organ niche. Very few human cells are expected to contribute to chimerism in heterologous animals.

Inflammatory Burden Index as a promising new marker for predicting surgical and oncological outcomes in colorectal cancer.

Aims: The prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short- and long-term outcomes in patients with CRC.

Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer.

Background: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC.

Methods: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360.

Complete Response to Pembrolizumab in a Patient with Castration-Resistant Prostate Cancer with Both BRCA Positivity and a High Frequency of Microsatellite Instability: A Case Report.

Introduction: There have been few reports of patients for whom a cancer gene panel test for solid tumors revealed the simultaneous presence of BRCA mutation and microsatellite instability (MSI)-high status. BRCA mutations have been reported in 13% of castration-resistant prostate cancer (CRPC) patients, and 3.1% of prostate cancer cases are MSI-high/mismatch repair deficient.

Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.

Background:  Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.

Objectives:  To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.

Methods:  For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.

CDK8/19 inhibitor enhances arginase-1 expression in macrophages via STAT6 and p38 MAPK activation.

Macrophages polarize into alternatively activated M2 macrophages through interleukin (IL)-4, and they express high levels of arginase-1, which promotes anti-inflammatory responses. Several studies have confirmed the anti-inflammatory effects of cyclin-dependent kinase (CDK) 8/19 inhibition, and hence, numerous CDK8/19 inhibitors, such as BRD6989, have been developed. However, the effects of CDK8/19 inhibitors on arginase-1 expression in macrophages have not yet been elucidated.

Role of sclerostin deletion in bisphosphonate-induced osteonecrosis of the jaw.

Purpose: Bone resorption inhibitors, such as bisphosphonates (BP) and denosumab, are frequently used for the management of osteoporosis. Although both drugs reduce the risk of osteoporotic fractures, they are associated with a serious side effect known as medication-related osteonecrosis of the jaw (MRONJ). Sclerostin antibodies (romosozumab) increase bone formation and decrease the risk of osteoporotic fractures: however, their anti-resorptive effect increases ONJ.

Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State.

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture.

Methoxylated Flavones from La Llave Suppress MMP9 Expression via Inhibition of the JAK/STAT3 Pathway and TNFα-Dependent Pathways.

Matrix metalloproteinase 9 (MMP9), an MMP isozyme, plays a crucial role in tumor progression by degrading basement membranes. It has therefore been proposed that the pharmacological inhibition of MMP9 expression or activity could inhibit tumor metastasis. We previously isolated two novel methoxylated flavones, casedulones A and B, from the leaves and/or roots of La Llave and determined that these casedulones have antitumor activity that acts via the reduction of MMP9.

Nuclear receptor 4A1 (NR4A1) upregulated by n-butylidenephthalide via the mitogen-activated protein kinase (MAPK) pathway ameliorates drug-induced gingival enlargement.

Drug-induced gingival enlargement (DIGE) is a side effect of ciclosporin, calcium channel blockers, and phenytoin. DIGE is a serious disease that leads to masticatory and esthetic disorders, severe caries, and periodontitis but currently has no standard treatment. We recently reported that nuclear receptor 4A1 (NR4A1) is a potential therapeutic target for DIGE.