Therapeutic Strategy for Fabry Disease by Intravenous Administration of Adeno-Associated Virus 9 in a Symptomatic Mouse Model.

Fabry disease (FD) is an inherited lysosomal storage disease caused by deficiency of α-galactosidase A (α-Gal A), an enzyme that hydrolyzes glycosphingolipids in lysosome. Accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3) in tissues, induces cellular dysfunction leading to multi-organ disorder. Gene therapy is a promising strategy that can overcome these problems, and virus vectors such as adeno-associated virus (AAV) have been used for study on gene therapy.

Asymmetric Henry Reaction Using Cobalt Complexes with Bisoxazoline Ligands Bearing Two Fluorous Tags.

The effect of the presence of fluorous tags in bisoxazoline ligands on the stereoselectivity of the cobalt-catalyzed asymmetric Henry reaction was investigated. In contrast to the stereoselectivity obtained with conventional nonfluorous ligands, using bisoxazoline bidentate ligands featuring two fluorous tags in adjacent positions on the aromatic ring yielded a reversed stereoselectivity. The stereoselectivity also reversed when the fluorous tags were replaced with alkyl chains of equivalent length, albeit to a considerably lesser degree, highlighting the effect of the fluorous tags.

Impact of post-progression survival in second-line treatment with molecular target agents for unresectable hepatocellular carcinoma.

Aim: Sequential therapies are essential to extend overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). Several second-line treatments with molecular target agents have shown survival benefits. However, the significance of post-progression survival (PPS) in extending OS in patients with HCC given such treatments remains uncertain.

Objective Response and Progression-Free Survival Contribute to Prolong Overall Survival in Atezolizumab plus Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma.

Introduction: Atezolizumab plus bevacizumab (Atez/Bev) is a standard treatment for unresectable hepatocellular carcinoma (HCC) due to its good antitumor and survival prolongation effects. Post-progression survival (PPS) has been reported to be a great contributor in the treatment with tyrosine kinase inhibitors for unresectable HCC. This study aimed to clarify the significance of progression-free survival (PFS) or PPS of Atez/Bev treatment for HCC.

Therapeutic strategy for Fabry disease by intravenous administration of adeno-associated virus 2 or 9 in α-galactosidase A-deficient mice.

Background: Fabry disease (FD) is an inherited lysosomal storage disease caused by deficiency of α-galactosidase A (α-Gal A) encoded by the GLA gene. The symptoms of FD occur as a result of the accumulation of globotriaosylceramide (Gb3), comprising a substrate of α-Gal A, in the organs. Adeno-associated virus (AAV)-mediated gene therapy is a promising treatment for FD.

Long term changes in thrombocytopenia and leucopenia after HCV eradication with direct-acting antivirals.

Background: Thrombocytopenia due to hypersplenism is a major complication of hepatitis C virus (HCV)-associated cirrhosis. HCV eradication improves these complications in some patients, but the long-term effects of HCV eradication on these complications remain unclear, especially in patients treated with direct acting antivirals (DAAs). The aim was to evaluate long term changes in thrombocytopenia and leucopenia after HCV eradication with DAAs.

Impact of Parkinson's Disease on Caregiver Quality of Life in Japan.

Background: Parkinson's disease (PD) adversely affects the quality of life (QoL) of not only patients but also their caregivers.

Objective: To determine the factors that most impact the QoL of family caregivers of patients with PD in a large Japanese population using data from the Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) study.

Methods: Questionnaires, including the Parkinson's Disease Questionnaire-Carer (PDQ-Carer), were distributed to patients and their caregivers.

Characterization of Influenza A(H1N1)pdm09 Viruses Isolated in the 2018-2019 and 2019-2020 Influenza Seasons in Japan.

The influenza A(H1N1)pdm09 virus that emerged in 2009 causes seasonal epidemic worldwide. The virus acquired several amino acid substitutions that were responsible for antigenic drift until the 2018-2019 influenza season. Viruses possessing mutations in the NA and PA proteins that cause reduced susceptibility to NA inhibitors and baloxavir marboxil, respectively, have been detected after antiviral treatment, albeit infrequently.

A ruptured sarcomatoid hepatocellular carcinoma treated with combined immunotherapy.

Sarcomatoid hepatocellular carcinoma (sHCC) is a rare phenotype of HCC with extremely poor prognosis and no established pharmacological treatment. Interventional therapies such as radiofrequency ablation (RFA) or transcatheter arterial embolization (TAE) have been shown to limit the development of sHCC through mechanisms involving hypoxia-induced epithelial-mesenchymal transition. This report describes an 83-year-old man who developed sHCC 2 years after RFA treatment for HCC and experienced sHCC rupture.

STAT6 gain-of-function variant exacerbates multiple allergic symptoms.

Background: Allergic diseases were long considered to be complex multifactorial disorders. However, recent findings indicate that severe allergic inflammation can be caused by monogenic immune defects.

Objectives: We sought to clarify the molecular pathogenesis of a patient with early-onset multiple allergic diseases, a high serum IgE level, hypereosinophilia, treatment-resistant severe atopic dermatitis with increased dermal collagen fiber deposition, and eosinophilic gastrointestinal disorder with numerous polypoid nodules.

Impact of Post-progression Survival on Outcomes of Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Retrospective Cohort Study.

Background/aim: Lenvatinib is a tyrosine kinase inhibitor (TKI) more effective against hepatocellular carcinoma (HCC) than sorafenib, making lenvatinib a first-line treatment option for patients with unresectable HCC. In patients treated with sorafenib, post-progression survival (PPS) rather than progression-free survival (PFS) is essential for overall survival (OS). However, the importance of PPS for OS in patients treated with lenvatinib is uncertain, and optimal treatment after lenvatinib failure has not yet been established.

A Case of Chronic Heart Failure Complicated by Primary Biliary Cholangitis and Skeletal Myopathy.

Several autoantigens related to inflammatory myopathy have been identified. Antimitochondrial antibody M2 (AMA-M2) is known as one of the serologic hallmarks of primary biliary cholangitis (PBC). There have been several reports on the association between AMA-M2 and various types of inflammatory myopathy, including cardiomyopathy.

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients has a high risk of recurrence. Although eradication of HCV is expected to reduce this risk, the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals (DAAs).

Aim: To determine the risk factors for HCC recurrence in patients with HCV and a history of HCC.

Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity.

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then-together with molecules derived from the circulation-promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT.

Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson's Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study.

Introduction: Deep brain stimulation (DBS) is an effective treatment for advanced Parkinson's disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.

Materials And Methods: Seventeen patients with Parkinson's disease (PwPD) who underwent unilateral GPi-DBS were selected.

A Case of Triple-Negative Breast Cancer with Germline Pathogenic Variants in Both and .

We report a rare case of hereditary breast and ovarian cancer syndrome (HBOC) with pathogenic variants in both and . The patient was a 78-year-old woman who visited the hospital after noticing a lump in her left breast 6 months before, which gradually increased in size. According to her family history, her maternal aunt developed breast cancer in her 40s.

Thermostability enhancement of l-glutamate oxidase from Streptomyces sp. NT1 by full consensus protein design.

Thermostable l-glutamate oxidases (LGOXs) are desirable for use in l-glutamate (L-Glu) assay kits, enzymatic synthesis of α-ketoglutarate and for biosensor development. However, protein engineering efforts to improve thermostability often lead to a decrease in enzymatic activity. In this report, we aimed to enhance the thermostability (melting temperature, T) of a mesophilic LGOX from Streptomyces sp.