Dual Inhibition of sEH and COX-2 Improved Cognition in Alzheimer's Disease via Enhanced Myogenic Response and Cerebral Artery Distensibility.

Genetic studies have linked (encoding soluble epoxide hydrolase, sEH) and (encoding cyclooxygenase-2, COX-2) to Alzheimer's disease (AD). Elevated levels of sEH and COX-2 found in AD patients and animals suggest their involvement in neurodegeneration, glial activation, vascular dysfunction, and inflammation. This study evaluated the effects of a new dual sEH/COX-2 inhibitor, PTUPB, on cerebrovascular function and cognition in TgF344-AD rats.

Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing.

Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds.

Comparative analysis of small molecule and growth factor-derived human induced pluripotent stem cell-derived hepatocyte-like cells.

The growth factor and small molecule protocol are the two primary approaches for generating human induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs). We compared the efficacy of the growth factor and small molecule protocols across fifteen different human iPSC lines. Morphological assessment, relative quantification of gene expression, protein expression and proteomic studies were carried out.

Vascular endothelial growth factor receptors 1 and 3 mediate placental trophoblast leptin production in preeclampsia, inducing vascular dysfunction.

Heightened soluble FMS-like tyrosine kinase-1 (sFlt-1) levels is a hallmark of preeclampsia patients and induces a state of angiogenic imbalance by sequestering free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The receptors for VEGF and PlGF, membrane-bound VEGFR, are expressed in placental trophoblast cells, but their functions are largely unknown. Placenta production of leptin significantly increases in preeclampsia, and we recently showed leptin induces placental and vascular endothelial dysfunction in pregnancy.

Myeloid-specific TFAM deficiency drives mitochondrial DNA stress and exacerbates allergic airway inflammation.

Asthma is the most prevalent chronic inflammatory lung disease in adolescents and young adults, characterized by persistent airway inflammation and remodeling. Increasing evidence indicates that activated lung macrophages play a significant role in the initiation, intensity, progression, and resolution of allergic airway inflammation. However, the underlying mechanisms regulating macrophage-mediated inflammation in asthma remain incompletely understood.

Efficient Generation of Induced Pluripotent Stem Cell-Derived Definitive Endoderm Cells with Growth Factors and Small Molecules.

Definitive endoderm (DE) differentiation leads to the development of the major internal organs including the liver, intestines, pancreas, gall bladder, prostate, bladder, thyroid, and lungs. The two primary methods utilized for differentiation of induced pluripotent stem cells (iPSCs) into DE cells are the growth factor (GF) and the small molecule (SM) approaches. The GSK-3 inhibitor (CHIR99021) is a key factor for the SM approach.

Balancing Reactivity and Specificity: Fc-Binding -Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248.

We report the design and synthesis of -acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound exhibits high water stability and >99% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing as a robust platform for efficient and site-selective antibody conjugation.

Unveiling the levels and significance of different serpin family proteins in aqueous humor dynamics.

Background: Alterations in the constituents of the aqueous humor (AH) are associated with various ocular pathologies, including primary open-angle glaucoma (POAG). AH contains a variety of immunomodulatory molecules, including serine protease inhibitors (serpins), which regulate several proteolytic cascades such as coagulation, angiogenesis, and inflammation. The purpose of this study was to examine the levels of different serpins in human AH and their association with POAG pathology.

Simultaneous Targeting of Tumor Cells and Tumor-Associated Macrophages To Reprogram Glioblastoma Using Trypsinized Extracellular Vesicles Carrying Tumor Suppressive MicroRNA.

Glioblastoma (GBM) remains difficult to treat due to poor drug delivery across the blood-brain barrier and an immunosuppressive tumor microenvironment (TME). Tumor-suppressive microRNAs (miRNAs) offer a promising strategy to reprogram both tumor cells and the TME, but inefficient delivery systems limit their clinical application. We previously reported that tumor-suppressive miR-138 regresses tumor growth in preclinical GBM models.

Exemption System for Economic Evaluation Data Submission for Pharmaceuticals in South Korea: Achievements and Challenges.

Objectives: Since the implementation of the positive listing system in South Korea in 2007, new and improved drugs have been reimbursed based on economic evaluation. Nevertheless, concerns have arisen about reduced accessibility to some drugs. To address this, an Exemption system for Economic Evaluation data submission for pharmaceuticals (EEE) was introduced in 2015 to improve access to drugs with uncertainties in evidence generation.

Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis.

There is a progressive decline in physiological function with age, and aging is associated with increased susceptibility to injury and infection. However, several reports have indicated that the agility of youth is characterized by transferable rejuvenating molecular factors, as was observed previously in heterochronic parabiosis experiments. These experiments demonstrated a rejuvenating effect of young blood in old animals.

IDH status dictates oHSV mediated metabolic reprogramming affecting anti-tumor immunity.

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma.

Targeting RBM39 with Tasisulam enhances TRAIL-induced apoptosis through DR5 upregulation and Bcl-2 downregulation in renal cell carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but faces limitations due to resistance mechanisms involving anti-apoptotic regulators such as Bcl-2. This study investigates Tasisulam, a molecular glue degrader, that degrades RNA-binding motif protein 39 (RBM39), as a sensitizer for TRAIL-mediated apoptosis in renal cell carcinoma (RCC). Tasisulam enhances TRAIL-induced apoptosis by activating both extrinsic and intrinsic apoptotic pathways, achieved through upregulation of death receptor 5 (DR5) and downregulation of B-cell lymphoma 2 (Bcl-2).

Development and Characterization of CD44-Targeted X-Aptamers with Enhanced Binding Affinity for Cancer Therapeutics.

CD44, a pivotal cell surface molecule, plays a crucial role in many cellular functions, including cell-cell interactions, adhesion, and migration. It serves as a receptor for hyaluronic acid and is involved in lymphocyte activation, recirculation, homing, and hematopoiesis. Moreover, CD44 is a commonly used cancer stem cell marker associated with tumor progression and metastasis.

PRMT5 inhibition sensitizes glioblastoma tumor models to temozolomide.

Background: Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, glioblastoma patients show dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma and its inhibition imparts an anti-tumor effect. Even though Temozolomide (TMZ) is the standard chemotherapeutic agent in the treatment of glioblastoma, tumor cells invariably develop resistance to TMZ.

Mass spectrometric detection of keratins in tear fluid.

Purpose: Keratin contamination is a common problem in mass spectrometry proteomic analyses, particularly in bottom-up mass spectrometry. The purpose of this study was to determine the protein contaminants introduced during the proteomic analysis of tear fluid.

Methods: Human tear fluid samples were collected using Schirmer strips.

Proteomic Alterations in Retinal Müller Glial Cells Lacking Interleukin-6 Receptor: A Comprehensive Analysis.

Purpose: Interleukin-6 (IL-6) is an inflammatory cytokine implicated in various retinal pathologies and functions primarily through two signaling pathways: cis-signaling via IL-6 binding to its membrane-bound receptor (IL-6Rα), and trans-signaling via IL-6 binding to soluble IL-6 receptor (sIL-6R). Because the differential effects of IL-6 signaling in retinal Müller glial cells (MGCs) remain unclear, we generated an MGC-specific Il6ra-/- knockout (KO) mouse to eliminate IL-6Rα and, consequently, IL-6 cis-signaling in MGCs. In this study, we examined the proteomic changes in MGCs isolated from KO mice lacking a functional IL-6Rα.

Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study.

Background And Objectives: The Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.

Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).

Perceptions of risk sharing agreements in South Korea from the viewpoints of key stakeholders: a convergent parallel mixed approach.

Objectives: In 2013, South Korea introduced risk-sharing agreements (RSAs) as a new reimbursement mechanism to enhance access to new medicines and to manage pharmaceutical expenditures. This study evaluates RSAs in South Korea from the viewpoints of key stakeholders.

Methods: In 2022, a survey and semi-structured interviews were conducted.

Recent advances in anticancer mechanisms of molecular glue degraders: focus on RBM39-dgrading synthetic sulfonamide such as indisulam, E7820, tasisulam, and chloroquinoxaline sulfonamide.

Synthetic sulfonamide anticancer drugs, including E7820, indisulam, tasisulam, and chloroquinoxaline sulfonamide, exhibit diverse mechanisms of action and therapeutic potential, functioning as molecular glue degraders. E7820 targets RBM39, affecting RNA splicing and angiogenesis by suppressing integrin α2. Phase I studies have demonstrated some stability in advanced solid malignancies; however, further efficacy studies are required.

Facile Size Tunable Skin-Adaptive Patch for Accelerating Wound Healing.

Owing to the moist and curved interfaces of skin wounds, enhancing the adhesiveness while maintaining delivery efficacy of biomolecules has drawn significant attention in advanced wound dressings. Despite tremendous trials to load biomolecules with sound adhesiveness, the complicated fabricating processes and abnormal allergic responses that are attributed to chemical moiety-based adhesives remain as major problems. To this end, in this study a one-step fabrication process is developed to manufacture microstructures with both a therapeutic (cylindrical structure for embossed structure human adipose-derived stem cell sheet, ESS) and an adhesive part (octopi-inspired structure of adhesive, OIA), which ESOIA is called.

The impact of ischemic stroke on bone marrow microenvironment and extracellular vesicles: A study on inflammatory and molecular changes.

An ischemic stroke (IS) is caused due to the lack of blood flow to cerebral tissue. Most of the studies have focused on how stroke affects the localized tissue, but it has been observed that a stroke can cause secondary complications in distant organs, such as Bone Marrow (BM). Our study focused on the effect of ischemic strokes on the bone marrow microenvironment.

Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.

Background: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

Methods: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance.

Optimizing polystyrene degradation, microbial community and metabolite analysis of intestinal flora of yellow mealworms, Tenebrio molitor.

This study explored a direct feeding of expanded polystyrene as the sole diet for breeding Tenebrio molitor larvae. Temperature and relative humidity were manipulated to evaluate polystyrene biodegradation efficiency, survival rate, and formation of micro-polystyrene residue. Efficient conditions were at temperature of 25 °C with a humidity of 65 ± 5 %.