Cheminformatic Read-Across Approach Revealed Ultraviolet Filter Cinoxate as an Obesogenic Peroxisome Proliferator-Activated Receptor γ Agonist.

This study introduces a novel cheminformatic read-across approach designed to identify potential environmental obesogens, substances capable of disrupting metabolism and inducing obesity by mainly influencing nuclear hormone receptors (NRs). Leveraging real-valued two-dimensional features derived from chemical fingerprints of 8435 Tox21 compounds, cluster analysis and subsequent statistical testing revealed 385 clusters enriched with compounds associated with specific NR targets. Notably, one cluster exhibited selective enrichment in peroxisome proliferator-activated receptor γ (PPARγ) agonist activity, prominently featuring methoxy cinnamate ultraviolet (UV) filters and obesogen-related compounds.

Prenylated Chrysin Derivatives as Partial PPARγ Agonists with Adiponectin Secretion-Inducing Activity.

Decreased circulating adiponectin levels are associated with an increased risk of human metabolic diseases. The chemical-mediated upregulation of adiponectin biosynthesis has been proposed as a novel therapeutic approach to managing hypoadiponectinemia-associated diseases. In preliminary screening, the natural flavonoid chrysin () exhibited adiponectin secretion-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs).

In vitro and in vivo suppression of SARS-CoV-2 replication by a modified, short, cell-penetrating peptide targeting the C-terminal domain of the viral spike protein.

Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino acids and evaluated its inhibitory effect against the replication of SARS-CoV-2 S clade and other variants.

Computational Prediction of the Phenotypic Effect of Flavonoids on Adiponectin Biosynthesis.

machine learning applications for phenotype-based screening have primarily been limited due to the lack of machine-readable data related to disease phenotypes. Adiponectin, a nuclear receptor (NR)-regulated adipocytokine, is relatively downregulated in human metabolic diseases. Here, we present a machine-learning model to predict the adiponectin-secretion-promoting activity of flavonoid-associated phytochemicals (FAPs).

Discovery of PPARγ and glucocorticoid receptor dual agonists to promote the adiponectin and leptin biosynthesis in human bone marrow mesenchymal stem cells.

Adiponectin and leptin are major adipocytokines that control crosstalk between adipose tissue and other organ systems. Hypoadiponectinemia and hypoleptinemia are associated with human metabolic diseases. Compounds with adipocytokine biosynthesis-stimulating activities could be developed as therapeutics against diverse metabolic conditions.

Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein.

The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication.

Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist.

The upregulation of adiponectin production has been suggested as a novel strategy for the treatment of metabolic diseases. Galangin, a natural flavonoid, exhibited adiponectin synthesis-promoting activity during adipogenesis in human bone marrow mesenchymal stem cells. In target identification, galangin bound both peroxisome proliferator-activated receptor (PPAR) γ and estrogen receptor (ER) β.

Sunscreen filter octocrylene is a potential obesogen by acting as a PPARγ partial agonist.

Octocrylene (OC) is an extensively prescribed organic ultraviolet B filter used in sunscreen products. Due to its extensive use, a significant level of OC is detected in marine and freshwater environments. Notably, the bioaccumulation of OC in aquatic biota may affect human health.

Analysis of the Anatomical Factors Associated with Cubital Tunnel Syndrome.

Background: Previous studies demonstrated that soft tissues, such as retinaculum, fibrous band, and anconeus, cause ulnar nerve compression, whereas other studies showed that the bony structures strain the ulnar nerve that runs directly behind the medial epicondyle constituting the boundary of the cubital tunnel during elbow flexion. However, no studies have reported the association of the shape of the bony structure with cubital tunnel syndrome symptoms. Are computed tomography (CT) and magnetic resonance imaging (MRI)-measured parameters of the bony cubital tunnel related to idiopathic cubital tunnel syndrome symptoms?

Hypothesis: We hypothesized that CT and MRI-measured parameters of the bony cubital tunnel were related to idiopathic cubital tunnel syndrome symptoms.

The Influence of Transverse Carpal Ligament Thickness on Treatment Decisions for Idiopathic Mild to Moderate Carpal Tunnel Syndrome.

Purpose: The main cause of carpal tunnel syndrome (CTS) is pathological changes in the flexor synovium, which is a known cause of pressure elevation in the carpal tunnel. The importance of the transverse carpal ligament (TCL) in the pathogenesis of CTS has hitherto been overlooked. However, the TCL significantly affects carpal biomechanics; the TCL is known to affect the carpal bone to a greater extent when intra carpal tunnel pressure is high.

Validity of computed tomographic measurements and morphological comparison of cubital tunnel in idiopathic cubital tunnel syndrome.

Background: Ulnar neuropathy is a common reason for referral to hand surgeons, and 10 to 30% of cubital tunnel syndrome (CuTS) is idiopathic. We hypothesized that the cause of idiopathic CuTS is in the bony structure.

Methods: We analyzed 79 elbows (39 idiopathic CuTS and 40 without CuTS symptom) using computed tomography and Materialize Mimics software to compare the differences between the two groups.

2-Phenyl-8-(1-phenylallyl)-chromenone compounds have a pan-PPAR modulator pharmacophore.

Adiponectin is an adipocytokine with insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties. Adiponectin secretion-inducing compounds have therapeutic potential in a variety of metabolic diseases. Phenotypic screening led to the discovery that 5,7-dihydroxy-8-(1-(4-hydroxy-3-methoxyphenyl)allyl)-2-phenyl-4H-chromen-4-one (compound 1) had adiponectin secretion-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs).

Activity of Daily Living After Long Level Fusion in Adult Spinal Deformity: Compared With Over 60-Year-Old Degenerative Spine Patients Without Adult Spinal Deformity.

Study Design: Prospective single center study.

Objective: The aim of this study was to evaluate 1) the activity of daily living (ADL) of three categorized patients group; over 60-year-old degenerative spine patients without adult spinal deformity (ASD), nonoperative ASD patients, and operative ASD patients, 2) what kinds of activities would be impaired, and 3) how the ADL changes over time after long level fusion.

Summary Of Background Data: There is still debate how surgeons could decide treatment methods for old-aged adult spinal deformity, operatively or not.

Blood loss after navigation-assisted minimally invasive total knee arthroplasty.

The following study evaluated blood loss in patients undergoing navigation-assisted minimally invasive total knee arthroplasty. The study included 100 patients divided into two groups. Group A consisted of patients with an immediate drain release, and group B consisted of patients with a 1-hour delayed drain release after surgery.

N-phenethyl-2-phenylacetamide isolated from Xenorhabdus nematophilus induces apoptosis through caspase activation and calpain-mediated Bax cleavage in U937 cells.

The present study was designed to assess the mechanism of N-phenethyl-2-phenylacetamide (NPPA), one of three new compounds isolated from Xenorhabdus nematophilus, on the induction of apoptosis in U937 cells. NPPA displayed strong inhibitory effects on cell proliferation and viability of U937 cells and induced apoptosis. Investigation of the mechanism of NPPA-induced apoptosis revealed that treatment with NPPA produced morphological features of apoptosis and DNA fragmentation.