Analysis of the Effects of Brefeldin A on Deuterium-Labeled Sphinganine Metabolism Using Liquid Chromatography-Tandem Mass Spectrometry.

Ceramide (Cer) is synthesized in the endoplasmic reticulum (ER) using sphinganine as the common backbone and is then transported to the Golgi apparatus to synthesize two complex sphingolipids, sphingomyelin (SM) and glucosylceramide (GlcCer). Brefeldin A (BFA) affects the structure of the Golgi apparatus, resulting in the redistribution of the Golgi proteins into the ER. Therefore, BFA has been used to examine the ER-to-Golgi trafficking of lipids, but the detailed lipid changes in cells upon BFA treatment are not fully understood.

Comparison of anti-SARS-CoV-2 activity of some commercial dairy products.

The continuing emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be ameliorated by infection prevention through daily diet. In this study, we examined the anti-SARS-CoV-2 activity of 10 commercially available dairy products. They did not show any cytotoxicity against VeroE6/transmembrane protease serine 2 (TMPRSS2) cells (CC > 4 mg/ml).

Model-based analysis to identify the impact of factors affecting electricity gaps during COVID-19: A case study in Germany.

The recent COVID-19 pandemic has precipitated drastic changes in economic and lifestyle conditions, significantly altering residual electricity demand behavior. This alteration has expanded the demand gap between actual and forecasted electricity usage based on pre-pandemic data, highlighting a critical global issue. Many studies in the pandemic have explored the features of this widening gap, which is impacted by major social events like fast virus spread and lockdowns.

Phospholipid Scramblase 1 Localizes Proximal to Sphingomyelin Synthase Isoforms but Is Not Involved in Sphingomyelin Synthesis.

Ceramide (Cer) is synthesized de novo in the bilayer of the endoplasmic reticulum and transported to the cytosolic leaflet of the trans-Golgi apparatus for sphingomyelin (SM) synthesis. As the active site of SM synthase (SMS) is located on the luminal side of the Golgi membrane, Cer translocates to the lumen via transbilayer movement for SM synthesis. However, the mechanism of transbilayer movement is not fully understood.

Onnamide A suppresses the severe acute respiratory syndrome-coronavirus 2 infection without inhibiting 3-chymotrypsin-like cysteine protease.

Given the continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of new inhibitors is necessary to enhance clinical efficacy and increase the options for combination therapy for the coronavirus disease 2019. Because marine organisms have been a resource for the discovery of numerous bioactive molecules, we constructed an extract library of marine invertebrates collected from the Okinawa Islands. In this study, the extracts were used to identify antiviral molecules against SARS-CoV-2.

Patient characteristics, diagnostic testing, and initial treatment profiles of patients with connective tissue disease-associated pulmonary arterial hypertension using a Japanese claims database.

Objectives: To investigate the diagnostic and therapeutic landscape for patients with connective tissue disease (CTD) and CTD-associated pulmonary arterial hypertension (CTD-PAH) in acute-care general hospitals in Japan.

Methods: We conducted a retrospective cohort study by analysing the Medical Data Vision (MDV) database from April 2008 to September 2020. CTD patients who prescribed immunosuppressants were included in cohort 1, and CTD-PAH patients extracted from cohort 1 were included in cohort 2.

Real-world diagnostic landscape and incidence of pulmonary hypertension in adult congenital heart disease patients using administrative claims data in Japan.

Background: Although pulmonary hypertension (PH) and Eisenmenger's syndrome (ES) are common complications in adult congenital heart disease (ACHD), the frequency of diagnostic tests and the incidence of PH/ES in patients with ACHD in Japanese clinical practice are unclear. Therefore, we sought to clarify the frequency of diagnostic tests and incidence of PH/ES in patients with ACHD using the Medical Data Vision (MDV) database, the largest anonymized database of diagnosis procedure combination hospitals in Japan.

Methods: We conducted a retrospective cohort study using the MDV database (April 2008 to December 2021) of patients with ACHD (International Classificaiton of Diseases, 10 revision codes: Q203-204, Q210-213, Q250) aged ≥15 years.

Optimal left ventricular diameter measurement in subjects with sigmoid septum: comparison with three-dimensional left ventricular volume.

Background: The purpose of this study was to determine the most appropriate measurement of left ventricular (LV) end-diastolic diameter for subjects with the sigmoid septum (SS) by measuring the LV end-diastolic diameter at the base and mid-ventricle and by examining the relationship between these measurements and the three-dimensional (3D) echocardiographic LV end-diastolic volume.

Methods: In 91 patients who underwent echocardiography for screening cardiovascular abnormalities, the aorto-septal angle (ASA) was measured as an index of the sigmoid septum. LV end-diastolic diameter was measured at the base and mid-ventricular level (DD and DD, respectively), and their average value was calculated (DD).

Reactive oxygen species are associated with the inhibitory effect of N-(4-hydroxyphenyl)-retinamide on the entry of the severe acute respiratory syndrome-coronavirus 2.

N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits the dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity. We previously reported that 4-HPR suppresses the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spike protein-mediated membrane fusion through a decrease in membrane fluidity in a DEGS1-independent manner. However, the precise mechanism underlying the inhibition of viral entry by 4-HPR remains unclear.

Anti-inflammatory Effect of a Combination of Cannabidiol and Extract on Lipopolysaccharide-stimulated RAW264 Macrophages.

Background/aim: The inflammatory response plays an important role in the activation and progression of many inflammation-related diseases. Cannabis sativa and Morinda citrifolia have long been used in folk medicine to treat inflammation. Cannabidiol is the most abundant non-psychoactive phytocannabinoid in C.

Dihydroceramide Δ4-Desaturase 1 Is Not Involved in SARS-CoV-2 Infection.

Dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity is inhibited with N-(4-hydroxyphenyl)-retinamide (4-HPR). We reported previously that 4-HPR suppresses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry through a DEGS1-independent mechanism. However, it remains unclear whether DEGS1 is involved in other SARS-CoV-2 infection processes, such as virus replication and release.

Cathepsin G-induced malignant progression of MCF-7 cells involves suppression of PAF signaling through induced expression of PAFAH1B2.

Breast cancer is primarily classified into ductal and lobular types, as well as into noninvasive and invasive cancer. Invasive cancer involves lymphatic and hematogenous metastasis. In breast cancer patients with distant metastases, a neutrophil-derived serine protease; cathepsin G (Cat G), is highly expressed in breast cancer cells.

Curcumae Longae Rhizoma and Saussureae Radix Inhibit Nitric Oxide Production and Cannabinoid Receptor 2 Down-regulation.

Background/aim: The cannabinoid 2 (CB2) receptor is an important regulator of immunoinflammatory responses. Crude drugs commonly used in Japanese traditional Kampo medicine have displayed anti-inflammatory effects; however, few studies have reported that these effects are mediated via CB2 receptor signaling. Therefore, this study aimed to elucidate CB2 receptor-related anti-inflammatory regulation in crude drugs.

Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis.

Introduction: Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor for renal anemia treatment, was evaluated in 5 phase 3 studies (MIYABI program). We report the results of the MIYABI hemodialysis-maintenance study.

Methods: This 52-week, randomized, double-blinded, double-dummy study compared the efficacy and safety of molidustat and darbepoetin in Japanese patients receiving hemodialysis and erythropoiesis-stimulating agents.

Efficacy and Safety of Molidustat for Anemia in ESA-Naive Nondialysis Patients: A Randomized, Phase 3 Trial.

Introduction: Molidustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that predominantly induces renal production of erythropoietin (EPO). Molidustat was evaluated for the treatment of anemia associated with chronic kidney disease (CKD) in the "Molidustat Once Daily Improves Renal Anemia by Inducing EPO" (MIYABI) program, which comprises 5 phase 3 clinical trials. The present MIYABI Non-Dialysis Correction (ND-C) study investigated the efficacy and safety of molidustat in Japanese patients with renal anemia who were not undergoing dialysis and were not receiving erythropoiesis-stimulating agent (ESA) treatment.

Molidustat for Renal Anemia in Nondialysis Patients Previously Treated with Erythropoiesis-Stimulating Agents: A Randomized, Open-Label, Phase 3 Study.

Introduction: Erythropoiesis-stimulating agents (ESAs) are the current standard of care for anemia due to chronic kidney disease (CKD) in patients not undergoing dialysis. Molidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated as an alternative treatment for renal anemia. Molidustat was evaluated in five phase 3 studies, the molidustat once daily improves renal anemia by inducing erythropoietin (MIYABI) program.

Anti-Inflammatory Effects of Extract against Lipopolysaccharide-Induced Inflammation in RAW264 Cells.

Leaves of (noni) have been used in Polynesian folk medicine for the treatment of pain and inflammation, and their juice is very popular worldwide as a functional food supplement. This study aimed to demonstrate that seed extract exerts anti-inflammatory effects on RAW264 cells stimulated by lipopolysaccharide. To confirm the inhibitory effect of seed extract, we assessed the production of nitric oxide (NO) and inflammatory cytokines.

Molidustat for the treatment of anemia in Japanese patients undergoing peritoneal dialysis: a single-arm, open-label, phase 3 study.

This 36-week, open-label, single-arm, phase 3 study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia undergoing peritoneal dialysis. Molidustat was titrated every 4 weeks to maintain Hb levels within the target range (≥11.0 and <13.

Lack of ∆5 Desaturase Activity Impairs EPA and DHA Synthesis in Fish Cells from Red Sea Bream and Japanese Flounder.

Long-chain (≥ C) polyunsaturated fatty acids (LC-PUFA), such as eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), are necessary for human health and are obtained from marine fish-derived oils. Marine fish are LC-PUFA-rich animals; however, many of them require LC-PUFA for growth. Therefore, it is suggested that they do not have sufficient ability to biosynthesize LC-PUFA.

-(4-Hydroxyphenyl) Retinamide Suppresses SARS-CoV-2 Spike Protein-Mediated Cell-Cell Fusion by a Dihydroceramide Δ4-Desaturase 1-Independent Mechanism.

The membrane fusion between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host cells is essential for the initial step of infection; therefore, the host cell membrane components, including sphingolipids, influence the viral infection. We assessed several inhibitors of the enzymes pertaining to sphingolipid metabolism, against SARS-CoV-2 spike protein (S)-mediated cell-cell fusion and viral infection. -(4-Hydroxyphenyl) retinamide (4-HPR), an inhibitor of dihydroceramide Δ4-desaturase 1 (DES1), suppressed cell-cell fusion and viral infection.