Nanocrystal Formulation to Enhance Oral Absorption of Silybin: Preparation, In Vitro Evaluations, and Pharmacokinetic Evaluations in Rats and Healthy Human Subjects.

Despite the various therapeutic benefits and high tolerance of orally administered silybin, poor water-solubility can be the main restrictive physicochemical feature, which results in low oral bioavailability in the absorption. A milk thistle nanocrystal formulation (HM40) was prepared using a modified wet-milling method. Comprehensive characterization was performed to determine the physical morphology, crystallinity, and physicochemical properties.

Effect of the Presence of Emergency Departments With 300 or More Hospital Beds in Health Service Areas on 30-Day Mortality in Korea: A Nationwide Retrospective Cross-sectional Study.

Background: Disparities in emergency care accessibility exist between health service areas (HSAs). There is limited evidence on whether the presence of an emergency department (ED) that exceeds a certain hospital bed capacity is associated with emergency patient outcomes at the regional level. The objective of this study was to evaluate the effect of HSAs with or without of regional or local emergency centers with 300 or more hospital beds (EC300 or nEC300, respectively) by comparing the 30-day mortality of patients with severe emergency diseases (SEDs) admitted to the hospital through the ED.

A Comparative Evaluation of HbA1c Measurement Methods and Their Implications for Diabetes Management.

In this study, we assessed the correlations between hemoglobin A1c (HbA1c) measurements obtained using three different diagnostic methods, namely reversed-phase cation-exchange chromatography, high-performance liquid chromatography, and lateral flow immunoassay (LIFA) with an AnyLab F instrument. HbA1c levels measured with the AnyLab F instrument and those measured with the HA8190V, HA8180, and D100 instruments were strongly correlated. High R-square values and low -values indicated significant and reliable correlations, supporting the clinical interchangeability of these methods.

Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer.

Background: Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18-C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established.

The N-degron pathway mediates lipophagy: The chemical modulation of lipophagy in obesity and NAFLD.

Background And Aims: Central to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is the accumulation of lipids in the liver and various fat tissues. We aimed to elucidate the mechanisms by which lipid droplets (LDs) in the liver and adipocytes are degraded by the autophagy-lysosome system and develop therapeutic means to modulate lipophagy, i.e.

Weekend effect on 30-day mortality for ischemic and hemorrhagic stroke analyzed using severity index and staffing level.

Background And Purpose: Previous studies on the weekend effect-a phenomenon where stroke outcomes differ depending on whether the stroke occurred on a weekend-mostly targeted ischemic stroke and showed inconsistent results. Thus, we investigated the weekend effect on 30-day mortality in patients with ischemic or hemorrhagic stroke considering the confounding effect of stroke severity and staffing level.

Methods: We retrospectively analyzed data of patients hospitalized for ischemic or hemorrhagic stroke between January 1, 2015, and December 31, 2018, which were extracted from the claims database of the National Health Insurance System and the Medical Resource Report by the Health Insurance Review & Assessment Service.

Mitophagy and endoplasmic reticulum-phagy accelerated by a p62 ZZ ligand alleviates paracetamol-induced hepatotoxicity.

Background And Purpose: Paracetamol (acetaminophen)-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. Autophagy is a degradative process by which various cargoes are collected by the autophagic receptors such as p62/SQSTM1/Sequestosome-1 for lysosomal degradation. Here, we investigated the protective role of p62-dependent autophagy in paracetamol-induced liver injury.

Matrix Metalloproteinase 1 as a Marker of Tonsil-Derived Mesenchymal Stem Cells to Assess Bone Marrow Cell Migration.

Background: To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient's bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration.

Palliative arthroscopic debridement with continuous irrigation for infected total knee arthroplasty in high mortality risk patients.

Purpose: This study aimed to evaluate the infection control rate of palliative arthroscopic debridement, antibiotics, and implant retention (DAIR) for the high mortality risk or terminal cancer stage patients.

Methods: From March 2018 to August 2021, 21 patients met the following inclusion criteria: old age of more than 80, diagnosed as a terminal stage of cancer, high risk of mortality and morbidity representing as Charlson comorbidity index (CCI) ≥ 5, low daily activity with disabled extremity, and re-infection after two-stage revision. Each patient underwent arthroscopic DAIR and additional continuous irrigation for 48 hours.

The Inlay Technique with Cortico-Cancellous Olecranon Bone Graft Used for Revision of Failed Distal Interphalangeal Joint Arthrodesis.

: Although distal interphalangeal (DIP) arthrodesis is an effective surgical method for end-stage osteoarthritis of the phalangeal joint, the nonunion rate of DIP arthrodesis has been reported to range from 15% to 20%. To this end, we devised an inlay technique with a cortico-cancellous olecranon bone graft for failed DIP arthrodesis. This study aimed to introduce the inlay bone grafting technique for failed arthrodesis of the DIP joint and demonstrate its advantages.

The Cys-N-degron pathway modulates pexophagy through the N-terminal oxidation and arginylation of ACAD10.

In the N-degron pathway, N-recognins recognize cognate substrates for degradation via the ubiquitin (Ub)-proteasome system (UPS) or the autophagy-lysosome system (hereafter autophagy). We have recently shown that the autophagy receptor SQSTM1/p62 (sequestosome 1) is an N-recognin that binds the N-terminal arginine (Nt-Arg) as an N-degron to modulate autophagic proteolysis. Here, we show that the N-degron pathway mediates pexophagy, in which damaged peroxisomal fragments are degraded by autophagy under normal and oxidative stress conditions.

Procollagen C-Endopeptidase Enhancer 2 Secreted by Tonsil-Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL-60 Cells.

Reactive oxygen species (ROS) generated by neutrophils provide a frontline defence against invading pathogens. We investigated the supportive effect of tonsil-derived mesenchymal stem cells (TMSCs) on ROS generation from neutrophils using promyelocytic HL-60 cells. Methods: Differentiated HL-60 (dHL-60) cells were cocultured with TMSCs isolated from 25 independent donors, and ROS generation in dHL-60 cells was measured using luminescence.

Promotion of Platelet Production by Co-Transplantation of Mesenchymal Stem Cells in Bone Marrow Transplantation.

Background: Therapeutic strategies that can promote platelet production are in demand to enhance clinical outcomes of bone marrow transplantation (BMT). Our research group has studied human tonsil-derived mesenchymal stem cells (T-MSCs) and their effectiveness in promoting bone marrow (BM) engraftment. Here, we analyzed the effects of T-MSCs on platelet production and hemostasis.

Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss.

Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size.

Prediction of Diabetic Sensorimotor Polyneuropathy Using Machine Learning Techniques.

Diabetic sensorimotor polyneuropathy (DSPN) is a major complication in patients with diabetes mellitus (DM), and early detection or prediction of DSPN is important for preventing or managing neuropathic pain and foot ulcer. Our aim is to delineate whether machine learning techniques are more useful than traditional statistical methods for predicting DSPN in DM patients. Four hundred seventy DM patients were classified into four groups (normal, possible, probable, and confirmed) based on clinical and electrophysiological findings of suspected DSPN.

Tonsil-derived mesenchymal stem cells enhance allogeneic bone marrow engraftment via collagen IV degradation.

Background: Co-transplantation of bone marrow cells (BMCs) and mesenchymal stem cells (MSCs) is used as a strategy to improve the outcomes of bone marrow transplantation. Tonsil-derived MSCs (TMSCs) are a promising source of MSCs for co-transplantation. Previous studies have shown that TMSCs or conditioned media from TMSCs (TMSC-CM) enhance BMC engraftment.

Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells.

(1) Background: six mammalian ceramide synthases (CerS1-6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22-C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice.

A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes.

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model.

A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells.

Background: The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period.

Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning.

Bone marrow (BM) transplantation (BMT) represents a curative treatment for various hematological disorders. Prior to BMT, a large amount of the relevant anticancer drug needed to be administered to eliminate cancer cells. However, during this pre‑BMT cytotoxic conditioning regimen, hematopoietic stem cells in the BM and thymic epithelial cells were also destroyed.

The role of sphingolipids in endoplasmic reticulum stress.

The endoplasmic reticulum (ER) is an important intracellular compartment in eukaryotic cells and has diverse functions, including protein synthesis, protein folding, lipid metabolism and calcium homeostasis. ER functions are disrupted by various intracellular and extracellular stimuli that cause ER stress, including the inhibition of glycosylation, disulphide bond reduction, ER calcium store depletion, impaired protein transport to the Golgi, excessive ER protein synthesis, impairment of ER-associated protein degradation and mutated ER protein expression. Distinct ER stress signalling pathways, which are known as the unfolded protein response, are deployed to maintain ER homeostasis, and a failure to reverse ER stress triggers cell death.

Conditioned Medium from Human Tonsil-Derived Mesenchymal Stem Cells Enhances Bone Marrow Engraftment via Endothelial Cell Restoration by Pleiotrophin.

Cotransplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) has been widely reported to promote HSC engraftment and enhance marrow stromal regeneration. The present study aimed to define whether MSC conditioned medium could recapitulate the effects of MSC cotransplantation. Mouse bone marrow (BM) was partially ablated by the administration of a busulfan and cyclophosphamide (Bu-Cy)-conditioning regimen in BALB/c recipient mice.

Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases.

The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals.