Characterization of soticlestat, a novel cholesterol 24-hydroxylase inhibitor, in acute and chronic neurodegeneration models.

We investigated whether soticlestat (TAK-935), a newly discovered cholesterol 24-hydroxylase (CH24H) inhibitor now in phase 3 clinical trials for Dravet and Lennox-Gastaut syndromes, has effects on neurodegeneration in both chronic and acute animal models associated with glutamate hyperexcitation. Soticlestat was administered at doses that approximately halve 24S-hydroxycholesterol in both experiments. In the kainic acid (KA)-induced acute hippocampal degeneration model, soticlestat ameliorated inflammatory cytokine expression, hippocampal degeneration, and memory impairment.

Investigating the Potential of Multilineage Differentiating Stress-Enduring Cells for Osteochondral Healing.

Objective: Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal stem cells (MSCs), have shown promise for various tissue repairs due to their stress tolerance and multipotent capabilities. We aimed to investigate the differentiation potential , the dynamics , and the reparative contribution of Muse cells to osteochondral lesions.

Design: Labeled MSCs were cultured and sorted into Muse and non-Muse (MSCs without Muse cells) groups.

Development and characterization of a chronic high intraocular pressure model in New Zealand white rabbits for glaucoma research.

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges.

Antibiotic effects on gut microbiota modulate diet-induced metabolic dysfunction-associated steatohepatitis development in C57BL/6 mice.

The potential involvement of the gut microbiota in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis has garnered increasing attention. In this study, we elucidated the link between high-fat/cholesterol/cholate-based (iHFC)#2 diet-induced MASH progression and gut microbiota in C57BL/6 mice using antibiotic treatments. Treatment with vancomycin (VCM), which targets gram-positive bacteria, exacerbated the progression of liver damage, steatosis, and fibrosis in iHFC#2-fed C57BL/6 mice.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

Integer-locking condition for stable dual-comb interferometry in situations with fluctuating frequency-comb repetition rates.

To make dual-comb interferometry usable in a wide range of applications, it is important to achieve reproducible measurement results even in non-ideal environments that affect the repetition-rate stability. Here, we consider dual-comb interferometry based on a pair of fully referenced optical frequency combs (OFCs) and investigate the impact of fluctuations in the OFC repetition frequencies on the peak position of the center burst in the interferogram. We identify a phase-locking scheme that minimizes the impact of these fluctuations through choosing a special combination of phase-locked frequencies, and the resulting type of operating condition is termed integer-locking condition.

Discovery and biological profile of pyridachlometyl.

Pyridachlometyl is a novel tubulin dynamics modulator fungicide developed by Sumitomo as a new agent designed to tackle fungicide resistance. Pyridachlometyl is being developed as a first-in-class molecule with an anti-tubulin mode of action, the chemical structure of which is characterized by a unique tetrasubstituted pyridazine ring. The first commercial product 'Fuseki flowable' received initial registration in 2023 in Japan.

Comparative Effectiveness of Different Er:YAG Laser-Activated Irrigation Systems on Removing Calcium Hydroxide from Simulated Internal Root Resorption Cavities at Different Root Levels.

To investigate the effectiveness of Er:YAG laser-activated irrigation (LAI) with a short pulse duration for removing calcium hydroxide (CH) from simulated internal root resorption (IRR) cavities at three root levels. Pulse duration is an important parameter during LAI, which ensures the efficiency of irradiation and the corresponding activation process. Short pulses in the range of a few microseconds enable rapid expansion and successive implosion of irrigants, resulting in distinct fluid movement.

Minimally Invasive Trans-sacral Canal Plasty for Lumbar Canal Stenosis.

Objective The elderly population is increasing in Japan. Along with the increase in the elderly population, the number of patients with lumbar degenerative diseases is also on the rise. In general, elderly patients tend to have more complications and are at higher risk for surgery.

The mechanism of multistep progression of the transcriptional cascade in activated microglia as approached by a proteome approach.

The ocular cytokine network plays pivotal roles in terms of the initiation and progression of retinal degeneration. Several types of immunocompetent cells such as microglia participate in inflammation, and a temporal transition in the molecular events of inflammation has been hypothesized. We previously found that the Csf2 gene was induced in the early phase of retinal degeneration.

Lung ultrasound in the assessment of interstitial lung disease in patients with connective tissue disease: Performance in comparison with high-resolution computed tomography.

Objective: To investigate clinical relevance of performing lung ultrasound (LUS) in patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) in comparison with high-resolution computed tomography (HRCT).

Methods: This single-centre study enrolled eligible patients with CTD-ILD from the prospective LUS registry. Total B-lines were detected by assessment at 14 sites via LUS.

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.

Background: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed.

Methods: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC.

Results: Of the patients included, 99 (50.

A pediatric case of Burkitt's lymphoma with bile duct obstruction requiring surgical biliary reconstruction.

Background: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases.

Altered projection-specific synaptic remodeling and its modification by oxytocin in an idiopathic autism marmoset model.

Alterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, utilizing a valproic acid-induced ASD marmoset model, which shares common molecular features with idiopathic ASD, we investigate changes in the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex through two-photon microscopy. In model marmosets, dendritic spine turnover is upregulated, and spines are generated in clusters and survived more often than in control marmosets.