Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (FADS1), delta-6 desaturase (FADS2), and elongase (ELOVL2) on changes in RBC and plasma biomarkers.
View Article and Find Full Text PDFBackground: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.
Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.
Purpose: Parkinson disease (PD) is a progressive neurodegenerative disease. The aim of this study is to investigate the association between acoustic and cortical brain features in Parkinson's disease patients.
Methods: We recruited 19 (eight females, 11 males) Parkinson's disease patients and 19 (eight females, 11 males) healthy subjects to participate in the experiment.
Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.
View Article and Find Full Text PDFSurface-enhanced Raman spectroscopy (SERS) has shown its ability to characterize biological substances down to a single-molecule level without a specific biorecognition mechanism. Various nanofabrication technologies enable SERS substrate prototyping and mass manufacturing. This study reports a complete cycle of design, fabrication, prototyping, and metrology of SERS substrates based on two-photon polymerization (2PP).
View Article and Find Full Text PDFChemotherapeutic agents, such as paclitaxel (PTX), induce neuroplastic changes and alter gene expression in the prefrontal cortex (PFC), which may be associated with chemotherapy-induced pain and negative emotions. Notably, DNA methylation undergoes adaptive changes in neurological disorders, emerging as a promising target for neuromodulation. In this study, systemic administration of PTX leads to a decrease in the expression of the DNA methyltransferase DNMT3a, while concurrently upregulating the expression of Gabrb1 mRNA and its encoded GABARβ1 protein in the medial PFC (mPFC) of male mice.
View Article and Find Full Text PDFBackground: Pulmonary embolism is an important cause of preventable mortality. Treatment strategies depend on risk stratification. High-risk patients, and some intermediate-high-risk patients, require urgent reperfusion therapy.
View Article and Find Full Text PDFBackground: This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs).
Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs.
Results: The frequency of category IV diagnoses (3.
Basic Clin Pharmacol Toxicol
January 2025
Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels.
View Article and Find Full Text PDFObjectives: To describe safety and efficacy of filgotinib 200 or 100 mg (FIL200/FIL100) in Japanese patients with rheumatoid arthritis in a long-term extension (LTE; NCT03025308).
Methods: Patients who completed any of three parent studies (NCT02889796: inadequate response [IR] to methotrexate [MTX]; NCT02873936: IR to biologic disease-modifying antirheumatic drugs; NCT02886728: MTX-naïve) without rescue therapy could enter the LTE; patients taking FIL continued their dosage, and those who received comparators were rerandomised to FIL200 or FIL100. This analysis includes week 156 interim results.
Decentralized clinical trials involving the use of digital tools to facilitate remote research are gaining momentum. Rapid advancements in digital technologies have supported the adoption of these trials. These innovations facilitate virtual interactions between clinical trial teams and participants by making it easier to collect, transfer and store electronic data.
View Article and Find Full Text PDFNeuropathic pain (NP) is a severe disease caused by a primary disease or lesion affecting the somatosensory nervous system. It is reported that NP is related to the increased activity of glutamatergic pyramidal cells and changed neural oscillations in the anterior cingulate cortex (ACC). Arginine vasopressin (AVP), a neurohypophyseal hormone, has been shown to cause pain-alleviating effects when applied to the peripheral system.
View Article and Find Full Text PDFDisruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue.
View Article and Find Full Text PDFThe interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.
View Article and Find Full Text PDFOne of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been the dependency on protein arginine methyltransferase 5 (PRMT5) in cancer cells with MTAP deletion. We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages. In vitro, PRMT5 inhibition induces DNA damage, cell cycle arrest, and aberrant alternative mRNA splicing in MTAP-deleted cells.
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