Publications by authors named "Charisse F Pasaje"

Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups at 8-position, which retained PI4K inhibitory activity but switched primary mode of action to the host hemoglobin degradation pathway through inhibition of hemozoin formation. These compounds showed minimal off-target inhibitory activity against the human phosphoinositide kinases and MINK1 and MAP4K kinases, which were associated with the teratogenicity and testicular toxicity observed in rats for the PI4K inhibitor clinical candidate MMV390048. A representative compound from the series retained activity against field isolates and lab-raised drug-resistant strains of .

View Article and Find Full Text PDF

Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth.

View Article and Find Full Text PDF

FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects.

View Article and Find Full Text PDF

The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNA(trp). Here we characterise two isoforms of TrpRS in Plasmodium; one eukaryotic type localises to the cytosol and a bacterial type localises to the remnant plastid (apicoplast).

View Article and Find Full Text PDF

Aminoacyl-tRNA synthetases are central enzymes in protein translation, providing the charged tRNAs needed for appropriate construction of peptide chains. These enzymes have long been pursued as drug targets in bacteria and fungi, but the past decade has seen considerable research on aminoacyl-tRNA synthetases in eukaryotic parasites. Existing inhibitors of bacterial tRNA synthetases have been adapted for parasite use, novel inhibitors have been developed against parasite enzymes, and tRNA synthetases have been identified as the targets for compounds in use or development as antiparasitic drugs.

View Article and Find Full Text PDF

Purpose: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6β (ATF6B) is known to regulate ATFα-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation.

View Article and Find Full Text PDF

Nasal polyps are abnormal lesions arising mainly from the nasal mucosa and paranasal sinuses. Since the human class II, major histocompatibility complex, transactivator (CIITA) is a positive regulator of class II, major histocompatibility complex gene transcription, the CIITA gene is thought to be involved in the presence of nasal polyps in asthma and aspirin hypersensitive patients. To investigate the association between CIITA and nasal polyposis, 18 single nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics who were classified into 158 aspirin-exacerbated respiratory disease (AERD) and 309 aspirin-tolerant asthma (ATA) subgroups.

View Article and Find Full Text PDF

Purpose: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).

View Article and Find Full Text PDF
Article Synopsis
  • Aspirin-exacerbated respiratory disease (AERD) is a severe condition in which ingestion of NSAIDs like aspirin leads to a significant drop in lung function (FEV1), and its genetic underpinnings are not fully understood.
  • In a study involving Korean asthmatics, researchers conducted a genome-wide association study (GWAS) to identify genetic factors linked to AERD, analyzing samples from patients both with and without the condition.
  • The results identified a significant association between the HLA-DPB1 gene polymorphism (specifically rs1042151) and AERD susceptibility, highlighting its potential role as a key genetic risk factor among Korean asthmatics.
View Article and Find Full Text PDF

Aspirin-exacerbated respiratory disease (AERD) is a respiratory disease characterized by acute bronchial responses upon the administration of non-steroidal anti‑inflammatory drugs (NSAIDs) and the immune response by mast cells is regarded as one of the noteworthy causes of AERD pathogenesis. The complement cascade is regarded as a key mechanism for clearing pathogens from the host. CD55 is one of the proteins involved in self-recognition, a central component of the complement system and autoimmunity.

View Article and Find Full Text PDF

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by bronchoconstriction after ingestion of nonsteroidal anti-inflammatory drugs including aspirin. The Ca concentration in bronchial epithelial cells is an important factor for bronchoconstriction. Human annexin A4 (ANXA4) is predominantly expressed in the secretory epithelia in the lung, stomach, intestine, and kidney.

View Article and Find Full Text PDF

Purpose: The human WD repeat-containing protein 46 (WDR46; also known as C6orf11), located at the disease-relevant centromere side of the class II major histocompatibility complex region, is hypothesized to be associated with risk of aspirin-exacerbated respiratory disease (AERD) as well as a decline in forced expiratory volume in the first second (FEV1), an important diagnostic marker of asthma.

Methods: To investigate the association between WDR46 and AERD, five single-nucleotide polymorphisms (SNPs) were genotyped in 93 AERD cases and 96 aspirin-tolerant asthma controls of Korean ethnicity. Three major haplotypes were inferred from pairwise comparison of the SNPs, and one was included in the association analysis.

View Article and Find Full Text PDF

Background And Aims: MicroRNAs have been recently identified as important regulators that influence human carcinogenesis, cancer progression, and the interaction between the host and virus. This study investigates an association between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver diseases through clearance of hepatitis B virus infection, development of liver cirrhosis, and hepatocellular carcinoma occurrence.

Methods: Genetic variations were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients.

View Article and Find Full Text PDF

The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population.

View Article and Find Full Text PDF

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells.

View Article and Find Full Text PDF

Background: Nasal polyps, part of the aspirin triad symptoms, are edematous protrusions arising from the mucosa of the nasal sinuses. Although the causative factors and pathogenesis of the polyps are unknown, the significant effect of human leukocyte antigen-DR (HLA-DR) expression in nasal polyps and genetic associations of the major histocompatibility complex class II, DR alpha (HLA-DRA) with immune-mediated diseases have been revealed.

Methods: To investigate the associations of HLA-DRA polymorphisms with nasal polyposis in asthmatic patients and in aspirin-hypersensitive subgroups, 22 single nucleotide polymorphisms (SNPs) were genotyped in a total of 467 asthmatic patients including 158 nasal polyp-positive and 309 polyp-negative subjects.

View Article and Find Full Text PDF

Background: The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned within the major histocompatibility complex (MHC) region which plays an important role in the immune system. In addition, DDR1 has been elucidated to be downregulated during the epithelial-mesenchymal transition of bronchial epithelium.

Objective: To investigate the potential genetic associations between DDR1 and aspirin-exacerbated respiratory disease (AERD), this study conducted association studies of DDR1 single nucleotide polymorphisms (SNPs) with AERD and the obstructive symptom of forced expiratory volume in 1 s (FEV(1)) decline after aspirin provocation.

View Article and Find Full Text PDF

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome that is characterized by nasal polyposis, general symptoms of asthma and sensitive response to non-steroidal anti-inflammatory drugs (NSAIDs). Although the exact function of tripartite motif-containing 26 (TRIM26) still remains unknown, the gene functions in the immune response. Thus, we hypothesized that TRIM26 polymorphisms may affect aspirin-induced bronchospasm and explored whether the gene can be a marker for diagnosis of AERD.

View Article and Find Full Text PDF

Background: Nasal polyps are abnormal lesions that cause airway obstruction and can occur along with other respiratory diseases. On account of its association with aspirin exacerbated respiratory disease (AERD), the human discoidin, CUB and LCCL domain containing 2 (DCBLD2) is hypothesized to be a candidate gene for the development of nasal polyps in asthma patients.

Methods: A total of 12 single-nucleotide polymorphisms (SNPs) were genotyped in 467 Korean asthma patients who were stratified further into 108 AERD and 353 aspirin-tolerant asthma (ATA) subgroups.

View Article and Find Full Text PDF

Airway remodeling and exacerbated airway narrowing in asthma have been attributed to the regulation of intracellular Ca(2+) by sarcoplasmic reticulum (SR) of the airway smooth muscle cells. The protein encoded by obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF (OBSCN) is a crucial factor in determining the SR architecture in Obscn(-/-) mice. This study genotyped a total of 55 common single-nucleotide polymorphisms (SNPs) in 592 Korean asthmatics including 163 aspirin exacerbated respiratory disease (AERD) cases and 429 aspirin-tolerant asthma (ATA) controls.

View Article and Find Full Text PDF

Background: Since subepithelial fibrosis and protruded extracellular matrix are among the histological characteristics of polyps, the emilin/multimerin domain-containing protein 2 (EMID2) gene is speculated to be involved in the presence of nasal polyps in asthma and aspirin-hypersensitive patients.

Methods: To investigate the association between EMID2 and nasal polyposis, 49 single-nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics of Korean ancestry who were stratified further into 114 aspirin exacerbated respiratory disease (AERD) and 353 aspirin-tolerant asthma (ATA) subgroups. From pairwise comparison of the genotyped polymorphisms, 14 major haplotypes (frequency > 0.

View Article and Find Full Text PDF

Modest effects of genes in various pathways are significant in the etiology of complex human diseases, including aspirin exacerbated respiratory disease (AERD). By functioning as a relevant component of respiratory processes, the human kinesin family member C1 (KIFC1) is hypothesized to play a role in AERD pathogenesis. A case-control analysis was carried out by comparing the genotype distribution of six KIFC1 single-nucleotide polymorphisms between 93 AERD cases and 96 aspirin-tolerant asthma controls in a Korean population.

View Article and Find Full Text PDF

Background: The functional role of the human diffuse panbronchiolitis critical region 1 (DPCR1) gene, located in the major histocompatibility complex class I, has not been widely investigated. However, this gene is a well known genetic marker for diffuse panbronchiolitis, a disease affecting human respiratory bronchioles. In this study we explored the association between polymorphisms in DPCR1 and aspirin-exacerbated respiratory disease (AERD), an asthma phenotype.

View Article and Find Full Text PDF

The RecA homolog, E. coli (S. cerevisiae) (RAD51) may modulate hepatitis B virus (HBV) infection by maintaining genome integrity and mediating homologous DNA repairs.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessioncvc5hks926fru0cqtckado05jkd4042e): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once