Drug repositioning of mesalamine via supramolecular nanoassembly for the treatment of drug-induced acute liver failure.

Acute liver failure (ALF) is characterized by rapid hepatic dysfunction, primarily caused by drug-induced hepatotoxicity. Due to the lack of satisfactory treatment options, ALF remains a fatal clinical disease, representing a grand challenge in global health. For the drug repositioning to ALF of mesalamine, which is clinically approved for the treatment of inflammatory bowel disease (IBD), we propose a supramolecular prodrug nanoassembly (SPNs).

Validation of artificial intelligence-based quantitative coronary angiography.

Background: Coronary angiography is fundamental for the diagnosis and treatment of coronary artery disease. Manual quantitative coronary angiography (QCA) is accurate and reproducible; however, it is time-consuming and labor-intensive. However, recent advancements in artificial intelligence (AI) have enabled automated and rapid analysis of medical images, addressing the need for real-time quantitative coronary analysis.

Exploring the potential of flour, starch concentrate, and protein concentrate from Richlea lentils in the development of lentil based extruded puffs.

Lentil puffs were developed from a mixed design of varying weight fractions of lentil flour (x1), lentil starch concentrate (x2), and lentil protein concentrate (x3) using a twin-screw pilot scale extruder at a dry feed rate of 20 kg/h (d.b.), a water feed rate of 2 kg/h, and an extruder screw speed of 350 rpm.

Targeting miR-21 to Overcome P-glycoprotein Drug Efflux in Doxorubicin-Resistant 4T1 Breast Cancer.

Acquired resistance to chemotherapy is a major challenge in the treatment of triple-negative breast cancer (TNBC). Despite accumulated evidence showing microRNA-21 (miR-21) as a vital regulator of tumor progression, the role of miR-21 in modulating the multidrug resistance of TNBC remains obscure. In this study, we demonstrate that miR-21 affects chemoresistance in 4T1 TNBC cells in response to doxorubicin (DOX) by regulating the P-glycoprotein (P-gp) drug efflux pump.

Milk-derived extracellular vesicles enable gut-to-tumor oral delivery of tumor-activated doxorubicin prodrugs.

Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Despite the current advancements in nanoparticle-mediated drug delivery, numerous anticancer drugs susceptible to the hostile gastrointestinal (GI) environment exhibit poor permeability across the intestinal epithelium, rendering them ineffective in providing therapeutic benefits. In this paper, we focus on harnessing milk-derived extracellular vesicles (mEVs) for gut-to-tumor oral drug delivery by leveraging their high bioavailability.

Effective descriptor extraction strategies for correspondence matching in coronary angiography images.

The importance of 3D reconstruction of coronary arteries using multiple coronary angiography (CAG) images has been increasingly recognized in the field of cardiovascular disease management. This process relies on the camera matrix's optimization, needing correspondence info for identical point positions across two images. Therefore, an automatic method for determining correspondence between two CAG images is highly desirable.

Dual-Action Protein-siRNA Conjugates for Targeted Disruption of CD47-Signal Regulatory Protein α Axis in Cancer Therapy.

A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and -acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors.

Targeted delivery of anti-miRNA21 sensitizes PD-L1 tumor to immunotherapy by promoting immunogenic cell death.

Growing evidence has demonstrated that miRNA-21 (miR-21) upregulation is closely associated with tumor pathogenesis. However, the mechanisms by which miR-21 inhibition modulates the immunosuppressive tumor microenvironment (TME) and improves tumor sensitivity to immune checkpoint blockade therapies remain largely unexplored. In this study, we demonstrate the precise delivery of anti-miR-21 using a PD-L1-targeting peptide conjugate (P21) to the PD-L1 TME.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect.

Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy.

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs).

Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

Background: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated.

Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography.

Oral TNF-α siRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease.

Oral administration facilitates the direct delivery of drugs to lesions within the small intestine and colon, making it an ideal approach for treating patients with inflammatory bowel disease. However, multiple physical barriers impede the delivery of oral RNA drugs through the gastrointestinal tract. Herein, we developed a novel oral siRNA delivery system that protects nucleic acids in extreme environments by employing exosomes derived from milk to encapsulate tumor necrosis factor-alpha (TNF-α) siRNA completely.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015-2017.

Background: Previous studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours.

Methods: We analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey.

Psychometric Properties of the Advance Care Planning Engagement Survey-9 in Cardiovascular and Metabolic Diseases.

The purpose of this study was to test the reliability and validity of the Advance Care Planning Engagement Survey-9 Korean version in patients with cardiovascular diseases or metabolic syndrome. In this cross-sectional study, data on advance care planning engagement, registration of advance directives and the intention, and sociodemographic characteristics were collected from 105 patients (mean age, 66.3 years) at 4 medical institutions.

Machine learning for predicting hepatitis B or C virus infection in diabetic patients.

Highly prevalent hepatitis B and hepatitis C virus (HBV and HCV) infections have been reported among individuals with diabetes. Given the frequently asymptomatic nature of hepatitis and the challenges associated with screening in some vulnerable populations such as diabetes patients, we conducted an investigation into the performance of various machine learning models for the identification of hepatitis in diabetic patients while also evaluating the significance of features. Analyzing NHANES data from 2013 to 2018, machine learning models were evaluated; random forest (RF), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO) along with stacked ensemble model.

Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery.

Background: Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production.

Physical Symptoms, Depressive Symptoms, and Quality of Life in Patients With Heart Failure: Cluster Analysis.

Background: Physical and psychological symptoms are prevalent in patients with heart failure (HF) and are associated with poor quality of life (QOL) and high hospitalization rates. Thus, it is critical to identify symptom clusters to better manage patients with high-risk symptom cluster(s) and to reduce adverse effects.

Objective: The aims of this study were to identify clusters of physical HF symptoms (ie, dyspnea during daytime, dyspnea when lying down, fatigue, chest pain, edema, sleeping difficulty, and dizziness) and depressive symptoms and to examine their association with QOL in patients with HF.

Diagnostic Value of a Wearable Continuous Electrocardiogram Monitoring Device (AT-Patch) for New-Onset Atrial Fibrillation in High-Risk Patients: Prospective Cohort Study.

Background: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation.

Objective: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHADS-VASc) score had increased detection rates.

Structural Relationships Between Cognitive Function, Depressive Symptoms, Self-Care Confidence, and Maintenance in Patients With Heart Failure.

Introduction: In order to promote self-care maintenance behavior in patients with heart failure (HF), it is necessary to identify the direct and indirect effects of major latent variables.

Objective: This study aimed to identify structural relationships between different domains of cognitive function, depression and self-care confidence, and self-care maintenance.

Methods: This descriptive study involved a secondary analysis using data of 201 patients with HF from two observational studies in three hospitals in Korea.

RNAi therapies: Expanding applications for extrahepatic diseases and overcoming delivery challenges.

The era of RNA medicine has become a reality with the success of messenger RNA (mRNA) vaccines against COVID-19 and the approval of several RNA interference (RNAi) agents in recent years. Particularly, therapeutics based on RNAi offer the promise of targeting intractable and previously undruggable disease genes. Recent advances have focused in developing delivery systems to enhance the poor cellular uptake and insufficient pharmacokinetic properties of RNAi therapeutics and thereby improve its efficacy and safety.

Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis.

Background: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease.