Publications by authors named "Doyoun Kim"
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer.
View Article and Find Full Text PDFSpondyloarthritis (SpA) is a chronic inflammatory disease that leads to ankylosis of the axial skeleton. Celecoxib (cyclooxygenase-2 inhibitor, COX-2i) inhibited radiographic progression in a clinical study of SpA, but in the following study, diclofenac (COX-2 non-selective) failed to show that inhibition. Our study aimed to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited bone progression in SpA, and whether celecoxib had a unique function (independent of the COX-inhibitor), compared with the other NSAIDs.
View Article and Find Full Text PDFAims: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance.
View Article and Find Full Text PDFArachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors.
View Article and Find Full Text PDFArticle Synopsis
- - ADNP syndrome is linked to developmental delays, intellectual disabilities, and autism spectrum disorders due to issues with the ADNP transcription factor in mice, particularly the Adnp-haploinsufficient (Adnp-HT) type.
- - Adnp-HT mice exhibit cognitive inflexibility and synaptic plasticity deficits, indicated by hyperactivity of the protein CaMKIIα, affecting their learning and memory capabilities and causing social deficits.
- - In adult Adnp-HT mice, the hippocampus shows elevated levels of phosphorylated CaMKIIα and prolonged long-term potentiation (LTP), which could be countered by inhibiting CaMKIIα, suggesting a link between ADNP deficiency and cognitive issues. *
Article Synopsis
- The study investigates the impact of albumin-bilirubin (ALBI) scores on the prognosis of colorectal cancer (CRC) patients after surgery.
- Researchers analyzed data from 723 surgical patients, comparing preoperative (ALBI-pre) and postoperative (ALBI-post) scores to determine their influence on overall survival (OS).
- The findings indicate that the combined ALBI-trend score (which considers changes from preoperative to postoperative scores) is a significant independent prognostic factor for OS, offering better predictive accuracy than ALBI-pre or ALBI-post scores alone.
Article Synopsis
- Parkinson's disease (PD) is linked to the degeneration of dopamine-producing neurons, leading to motor dysfunction, but physical therapy, especially motor skill learning training, shows promise for improvement.
- A study using rotarod walking exercise (RWE) on a mouse model of PD showed significant enhancements in motor function and reductions in dopaminergic neuron death, alongside increased expression of neuroprotective factors and improved inflammation markers.
- RWE also reduced the harmful forms of α-synuclein, suggesting that this exercise may help mitigate neuroinflammation and improve PD pathology, highlighting its potential as a therapeutic approach.
BZ Junctions and Its Application as Probe (2AP) to Detect Z-DNA Formation and Its Effector.
Methods Mol Biol
March 2023
Article Synopsis
- The study focuses on the junction where left-handed Z-DNA meets right-handed B-DNA, highlighting the formation of this junction over time in the genome.
- The BZ junction has a unique base extrusion structure that could assist in identifying Z-DNA formation within DNA strands.
- Researchers explain how to detect this BZ junction structure using a fluorescent probe called 2-aminopurine (2AP), which allows measurement in solution.
Crystallization of Z-DNA in Complex with Chemical and Z-DNA Binding Z-Alpha Protein.
Methods Mol Biol
March 2023
Article Synopsis
- The molecular recognition and stabilization of Z-DNA is primarily understood through X-ray crystallography, which helps visualize its structure.
- Z-DNA forms when sequences alternate between purine and pyrimidine, but creating this structure requires energy, necessitating the use of small stabilizers or specific binding proteins.
- The text details the methods used for preparing DNA and the Z-alpha protein, along with the process for crystallizing Z-DNA.
Article Synopsis
- * Research on Arid1b-happloinsufficient mice indicates that they exhibit behaviors similar to autism and have reduced excitatory synaptic density during both juvenile and adult stages.
- * Chronic fluoxetine treatment in Arid1b mice during early postnatal weeks prevents these deficits, leading to positive transcriptomic changes that regulate synaptic protein expression, suggesting early intervention can have lasting benefits.
Protein interactome and cell-type expression analyses reveal that cytoplasmic FMR1-interacting protein 1 (CYFIP1), but not CYFIP2, associates with astrocytic focal adhesion.
J Neurochem
July 2022
Article Synopsis
- The study investigates the two proteins, CYFIP1 and CYFIP2, which have similar structures but different functions in the brain and are linked to various brain disorders.
- Experiments show that these proteins do not interact significantly with each other and have distinct distributions in brain cells, with CYFIP1 found in both neurons and astrocytes while CYFIP2 is primarily in neurons.
- Analysis of the proteins they interact with indicates that CYFIP1 is specifically associated with astrocytic focal adhesion, suggesting a unique role for CYFIP1 in brain function that differs from CYFIP2.
Article Synopsis
- Protein lysine acetylation is a modification that affects protein function, with specific enzymes (KATs) adding and removing acetyl groups from proteins, influencing their activity and interactions.* -
- The study reveals that the KAT enzyme GCN5 plays a critical role in muscle integrity by inhibiting the transcription factor YY1, which, when disrupted, leads to decreased expression of essential muscle proteins and causes myopathy.* -
- Findings indicate that GCN5's acetylation of YY1 prevents it from binding to DNA, suggesting that maintaining protein acetylation could be key for muscle health and could guide new treatments for muscle-related diseases.*
Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain.
View Article and Find Full Text PDFSynaptic adhesion molecules regulate synapse development through trans-synaptic adhesion and assembly of diverse synaptic proteins. Many synaptic adhesion molecules positively regulate synapse development; some, however, exert negative regulation, although such cases are relatively rare. In addition, synaptic adhesion molecules regulate the amplitude of post-synaptic receptor responses, but whether adhesion molecules can regulate the kinetic properties of post-synaptic receptors remains unclear.
View Article and Find Full Text PDFArticle Synopsis
- The novel coronavirus, SARS-CoV-2, emerged in December 2019 in Wuhan, China, resulting in over 3.6 million confirmed COVID-19 cases and over 254,000 deaths by May 2020, presenting a significant global health challenge.
- Despite the urgent need, there are currently no approved antiviral treatments specifically for COVID-19, prompting efforts to repurpose existing antiviral drugs used for other viruses like HIV and Ebola.
- The review emphasizes the importance of combining repurposed drugs and employing structure-based drug design to target the virus effectively, while also discussing the structural features of potential therapeutic targets related to COVID-19.
Article Synopsis
- DYRK1A is a crucial gene for human development, and its haploinsufficiency can cause a recognizable syndrome with varying symptoms, including facial features and developmental delays.
- A patient with DYRK1A haploinsufficiency syndrome was identified with specific mutations leading to a truncated protein that is unstable and inactive.
- Experiments in cell and fruit fly models demonstrated that the mutated DYRK1A protein has minimal effects on normal functions, supporting the idea that its loss-of-function contributes to the patient's developmental issues.
Article Synopsis
- A mutation in the Glutamate receptor, specifically GluN2B (GRIN2B), is linked to neurodevelopmental disorders like autism, but how this works isn't fully understood.
- Researchers created mice with a specific mutation (Grin2b+/C456Y) that showed reduced GluN2B protein, leading to decreased receptor activity and abnormal behavior without affecting social interaction.
- Early treatment with the NMDAR agonist D-cycloserine improved receptor function and anxiety-like behavior, suggesting that early intervention could have lasting benefits on brain function and behavior.
Article Synopsis
- Synaptic adhesion molecules influence how synapses develop and work, but little is known about how presynaptic molecules affect postsynaptic NMDAR function.
- The study shows that presynaptic PTPσ, a type of receptor tyrosine phosphatase, boosts postsynaptic NMDAR activity and related synaptic changes in the hippocampus without relying on direct adhesion between cells.
- It also finds that changes in phosphotyrosine levels in presynaptic proteins are significant in PTPσ-mutant mice and suggests that PTPσ plays a critical role in social and reward-related recognition behaviors.
Article Synopsis
- Mutations in the TBR1 gene, linked to autism spectrum disorder (ASD), cause various dysfunctions in mice, indicating their potential impact on ASD-related behaviors and biology.
- Researchers created mice with the human-specific TBR1-K228E mutation and observed higher levels of the non-functional TBR1 protein, leading to significant changes in gene expression in the embryonic brain.
- The mice exhibited notable ASD-related characteristics, including reduced social interaction, increased self-grooming, and signs of anxiety, highlighting the mutation's role in affecting both molecular and behavioral aspects of ASD.
Article Synopsis
- - Shank3 is a protein linked to excitatory synapse regulation and is associated with various brain disorders, including autism spectrum disorders (ASD) and schizophrenia.
- - Researchers created a knock-in mouse model with the Q321R mutation found in a person with ASD, leading to a selective decrease in a specific variant of Shank3, impacting neuronal excitability while maintaining normal synaptic transmission.
- - Mice with the mutation displayed enhanced self-grooming and anxiety-like behavior, normal social interactions, altered EEG patterns, and were less prone to seizures, suggesting the mutation affects multiple aspects of behavior and brain function.
Haploinsufficiency in Mice Suppresses Hippocampal Neuronal Excitability, Excitatory Synaptic Drive, and Long-Term Potentiation, and Spatial Learning and Memory.
Front Mol Neurosci
June 2019
Nav1.2, a voltage-gated sodium channel subunit encoded by the gene, has been implicated in various brain disorders, including epilepsy, autism spectrum disorder, intellectual disability, and schizophrenia. Nav1.
View Article and Find Full Text PDFBackground: Autism spectrum disorder involves neurodevelopmental dysregulations that lead to visible symptoms at early stages of life. Many autism spectrum disorder-related mechanisms suggested by animal studies are supported by demonstrated improvement in autistic-like phenotypes in adult animals following experimental reversal of dysregulated mechanisms. However, whether such mechanisms also act at earlier stages to cause autistic-like phenotypes is unclear.
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