MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2.

Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, strategies for activating the Tie2 signaling pathway have been developed as potential therapies for neurovascular diseases.

A novel targeted anticancer drug delivery strategy: Cnidium officinale polysaccharide conjugated with carboxymethyl-5-fluorouracil and folic acid for ovarian cancer therapy.

To mitigate adverse reactions induced by 5-fluorouracil (5-FU), Cnidium officinale fraction 2 (F2) polysaccharides served as the macromolecular carrier, facilitating its reaction with carboxymethyl-5-fluorouracil (C-5-FU) for producing F2-C-5-FU. Subsequently, this compound could react with folic acid (FA) through the ester bond, forming F2-C-5-FU-FA, as verified through NMR analysis. The in vitro anticancer efficacy of F2-C-5-FU-FA was evaluated using SKOV-3 cells that expressed folate receptor (FR) and FR-deficient A549 cells, showing greater cytotoxicity in the SKOV-3 cell line due to the FRs on the cell membrane.

Folic-acid-targeted drug delivery system implementing Angelica gigas polysaccharide: A potential strategy for colorectal cancer treatment.

The study focuses on the development of folate-targeted conjugates utilizing Angelica gigas polysaccharide (F2) as a drug carrier for colorectal cancer therapy. We synthesized F2-C-5-FU conjugates by linking carboxymethyl-5-fluorouracil (C-5-FU) with folic acid (FA) through ester bonding. The drug release behavior of F2-C-5-FU-FA was pH-dependent, favoring release under alkaline conditions.

Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model.

Purpose: To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury.

Materials And Methods: A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment.

DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice.

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated.

Angelica gigas polysaccharide induces CR3-mediated macrophage activation and the cytotoxicity of natural killer cells against HCT-116 cells via NF-κB and MAPK signaling pathways.

Angelica gigas (A. gigas) is traditional medicinal herb that mainly exists in Korea and northeastern China. There have been relatively few studies conducted thus far on its polysaccharides and their bioactivities.

BMP2 restores erectile dysfunction through neurovascular regeneration and fibrosis reduction in diabetic mice.

Background: The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase-5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis.

Benzisothiazolinone: Pharmacokinetics, Tissue Distribution, and Mass Balance Studies in Rats.

Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration.

Cancer-specific functional profiling in microsatellite-unstable (MSI) colon and endometrial cancers using combined differentially expressed genes and biclustering analysis.

Microsatellite-unstable (MSI) cancers have distinct genetic and clinical features from microsatellite-stable cancers, but the molecular functional differences between MSI cancers originating from different tissues or organs have not been well studied because the application of usual differentially expressed gene (DEG) analysis is error-prone, producing too many noncancer-specific normally functioning genes. To maximize therapeutic efficacy, biomarkers reflecting cancer-specific differences between MSI cancers of different tissue origins should be identified. To identify functional differences between MSI colon and endometrial cancers, we combined DEG analysis and biclustering instead of DEG analysis alone and refined functionally relevant biclusters reflecting genuine functional differences between the 2 tumors.

Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice.

Purpose: Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear.

A novel sulfated mannan-carboxymethyl-5-fluorouracil-folic acid conjugates for targeted anticancer drug delivery.

CFP is a sulfated polysaccharide isolated from Codium fragile that shows excellent immunomodulatory activity. To reduce the side effects of 5-fluorouracil (5-FU), CFP was used as a macromolecular carrier to react with carboxymethyl-5-fluorouracil (C-5-FU) to form CFP-C-5-FU, which further reacted with folic acid (FA) via an ester bond to form novel conjugates (CFP-C-5-FU-FA). CFP-C-5-FU-FA was confirmed by nuclear magnetic resonance (NMR) analysis.

CD14+ monocytes and soluble CD14 of synovial fluid are associated with osteoarthritis progression.

Objectives: This study aims to investigate the role of cluster of differentiation 14 (CD14) expressed monocytes and soluble CD14-mediated pathway in the synovial inflammation of knee osteoarthritis (OA).

Patients And Methods: Between May 2012 and July 2013, a total of 35 patients with knee OA (9 males, 26 females; mean age: 66.3±8.

Accelerator mass spectrometry for quantification of micro- and therapeutic-dose diclofenac in microdialysis samples.

Microdialysis sampling after drug microdosing may provide tissue pharmacokinetic data early in clinical drug development. However, low administered doses and small sample volumes pose an analytical challenge, particularly for highly protein-bound drugs. Carbon-14 [C]diclofenac was used as a model drug to assess the technical and analytical feasibility of microdialysis after microdose administration in an setup.

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM.

Pericyte‑derived extracellular vesicles‑mimetic nanovesicles improves peripheral nerve regeneration in mouse models of sciatic nerve transection.

Pericyte‑derived extracellular vesicle‑mimetic nanovesicles (PC‑NVs) play an important role in the improvement of erectile function after cavernous nerve injury. However, the impact of PC‑NVs on the peripheral nervous system (PNS), such as the sciatic nerve, is unclear. In this study, PC‑NVs were isolated from mouse cavernous pericytes (MCPs).

Association between previous rheumatoid arthritis and COVID-19 and its severity: a nationwide cohort study in South Korea.

Objectives: The prevalence of rheumatoid arthritis (RA) among patients with COVID-19 and the association between RA and the outcome of COVID-19 remain unclear. We aimed to compare the prevalence of RA between participants with and without COVID-19; we then analysed the association between the presence of RA and the severity of COVID-19.

Design: A cross-sectional study.

RNA-sequencing profiling analysis of pericyte-derived extracellular vesicle-mimetic nanovesicles-regulated genes in primary cultured fibroblasts from normal and Peyronie's disease penile tunica albuginea.

Background: Peyronie's disease (PD) is a severe fibrotic disease of the tunica albuginea that causes penis curvature and leads to penile pain, deformity, and erectile dysfunction. The role of pericytes in the pathogenesis of fibrosis has recently been determined. Extracellular vesicle (EV)-mimetic nanovesicles (NVs) have attracted attention regarding intercellular communication between cells in the field of fibrosis.

Comparison of the 2017 EULAR/ACR Criteria with Clinicoserologic Criteria for the Classification of Idiopathic Inflammatory Myopathies in Korean Patients.

Purpose: To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients.

Materials And Methods: We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review.

Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats.

2-Phenoxyethanol (PE), ethylene glycol monophenyl ether, is widely used as a preservative in cosmetic products as well as in non-cosmetics. Since PE has been used in many types of products, it can be absorbed via dermal or inhaled route for systemic exposures. In this study, the pharmacokinetic (PK) studies of PE and its major metabolite, phenoxyacetic acid (PAA), after dermal (30 mg and 100 mg) and inhaled administration (77 mg) of PE in rats were performed.

Mediation effects of clinical practice stress between clinical education environment and satisfaction with clinical practice.

Purpose: The purpose of this study was to identify the possible correlations of 'satisfaction with clinical practice (SA)' with 'clinical learning environment (EN)' and 'clinical practice stress (ST).' We searched for the mediating effect of 'clinical practice stress' on 'satisfaction with clinical practice' when the clinical learning environment influences 'satisfaction with clinical practice.'

Methods: This research investigated 208 medical and nursing students attending the school of medicine and nursing in Korea.

Pericyte-Derived Extracellular Vesicle-Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury.

Background: Extracellular vesicle (EV)-mimetic nanovesicles (NVs) from embryonic stem cells have been observed to stimulate neurovascular regeneration in the streptozotocin-induced diabetic mouse. Pericytes play important roles in maintaining penile erection, yet no previous studies have explored the effects of pericyte-derived NVs (PC-NVs) in neurovascular regeneration in the context of erectile dysfunction.

Aim: To investigate the potential effect of PC-NVs in neurovascular regeneration.

Embryonic stem cell-derived extracellular vesicle-mimetic nanovesicles rescue erectile function by enhancing penile neurovascular regeneration in the streptozotocin-induced diabetic mouse.

Extracellular vesicles (EVs) have attracted particular interest in various fields of biology and medicine. However, one of the major hurdles in the clinical application of EV-based therapy is their low production yield. We recently developed cell-derived EV-mimetic nanovesicles (NVs) by extruding cells serially through filters with diminishing pore sizes (10, 5, and 1 μm).