In-frame deletion variant of ABCD1 in a sporadic case of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.

Prenatal exposure to metal mixture and birth weight; a Bayesian kernel machine regression analysis of two cohort studies in Japan and Iran.

Purpose: Potentially toxic metals can directly induce various adverse effects on reproductive organs or interrupt essential metals' physiological activities. Despite intensive efforts to reduce these metals in the environment, chronic and low-level exposure remains a public health problem. The present study aimed to investigate prenatal metal exposure, including arsenic (As), copper (Cu), lead (Pb), manganese (Mn), rubidium (Rb), selenium (Se), and zinc (Zn), effects on birth weight.

CML With Mutant ASXL1 Showed Decreased Sensitivity to TKI Treatment via Upregulation of the ALOX5-BLTR Signaling Pathway.

In this study, the mechanisms of tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML) were investigated focusing additional sex combs-like 1 (ASXL1) gene mutations and their downstream effects. While TKIs have improved the prognosis of CML, some patients have shown resistant to therapy. Cases with mutations in epigenome-related genes such as ASXL1 are known to have a poor prognosis, but the underlying mechanisms of the poor prognosis are unclear.

Clinical and Genetic Analyses of SPG7 in Japanese Patients with Undiagnosed Ataxia.

Objective Spastic paraplegia 7 (SPG7) is an autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in SPG7. It is predominantly characterized by adult-onset slowly progressive spastic paraparesis. While SPG7 presenting with ataxia with or without spasticity is relatively common in Europe and North America, it is considered rare in Japan.

Plasma membrane-coated nanoparticles and membrane vesicles to orchestrate multimodal antitumor immunity.

Background: A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit.

A subgroup of multiple system atrophy with rapid decline in vital capacity.

Introduction: Patients with neurodegenerative disorders resulting in progressive dysphagia often require gastrostomy. Pulmonary function tests (PFTs) are crucial in presurgical evaluation; however, reports on pulmonary function in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are limited.

Materials And Methods: This single-center, retrospective study analyzed the PFT records from patients with MSA and PSP admitted between January 2012 and October 2023.

Understanding the impact of spatial immunophenotypes on the survival of endometrial cancer patients through the ProMisE classification.

Objectives: We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.

Patients And Methods: Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software.

A Japanese Family with a Novel Pathogenic Variant in KIF1A Presenting with Spastic Paraparesis, Cerebellar Ataxia, and Intellectual Disability.

Variants in KIF1A are associated with hereditary spastic paraplegia (SPG30), which can manifest in both pure and complex forms. We describe a Japanese family with a novel KIF1A variant presenting with a complex form of SPG30. Patient 1, a 69-year-old woman, experienced progressive gait disturbance due to spastic paraparesis and cerebellar atrophy, and intellectual disability.

A Novel Quaternary Ammonium N-Propylamiodarone Bromide Provides Long-Lasting Analgesia Against Corneal Pain.

Purpose: Corneal pain is one of the most common eye symptoms caused by various types of epithelial injuries, including traumatic abrasion, chemical injury, ulcers, ultraviolet exposure, and infection. However, current therapeutic options for corneal pain are limited. In this study, we synthesized a novel quaternary ammonium compound, N-propylamiodarone bromide (NPA), and employed a rodent model of corneal injury to investigate whether NPA offers prolonged corneal analgesia through transient receptor potential vanilloid 1 (TRPV1) channel-mediated selective cellular entry, without hindering corneal epithelial recovery.

Designing strong inducible synthetic promoters in yeasts.

Inducible promoters are essential for precise control of target gene expression in synthetic biological systems. However, engineering eukaryotic promoters is often more challenging than engineering prokaryotic promoters due to their greater mechanistic complexity. In this study, we describe a simple and reliable approach for constructing strongly inducible synthetic promoters with minimum leakiness in yeasts.

A Case of Wilson's Disease Preceded by Schizophrenia-like Symptoms with Frontal-dominant Leukoencephalopathy.

We herein report a 26-year-old man diagnosed with Wilson's disease (WD), initially treated for schizophrenia for 11 years. At 26 years old, he was admitted because of status epilepticus. Brain magnetic resonance imaging revealed frontal-dominant leukoencephalopathy with cystic changes and basal ganglia atrophy.

FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting.

Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion.

Purpose: S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia-reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway.

Cardioprotective effects of l-glutamine in an ischemic rat heart model.

Introduction: l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied.

Methods: This study hypothesized that l-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only.

GULP1 as a Downstream Effector of the Estrogen Receptor-β Modulates Cisplatin Sensitivity in Bladder Cancer.

Background/aim: Precise molecular mechanisms underlying resistance to cisplatin-based chemotherapy remain unclear, while the activity of estrogen receptor-β (ERβ) has been suggested to be associated with chemosensitivity in urothelial cancer. We aimed to determine if GULP1, an adapter protein known to facilitate phagocytosis, could represent a downstream effector of ERβ and thereby modulate cisplatin sensitivity in bladder cancer.

Materials And Methods: GULP1 expression and cisplatin cytotoxicity were compared in bladder cancer lines.

PGC1α as a downstream effector of KDM5B promotes the progression of androgen receptor-positive and androgen receptor-negative prostate cancers.

PPARγ coactivator-1α (PGC1α), as a co-activator, is known to optimize the action of several transcription factors, including androgen receptor (AR). However, the precise functions of PGC1α in prostate cancer, particularly those via the non-AR pathways, remain poorly understood. Meanwhile, our bioinformatics search suggested that PGC1α could be a direct downstream target of lysine-specific demethylase 5B (KDM5B/JARID1B/PLU1).

A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy.

We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia.