Publications by authors named "Kwangho Kim"

Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.

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Article Synopsis
  • Barium titanate (BaTiO) is notable for its high dielectric constant and piezoelectric properties, making it crucial for sustainable energy devices, but challenges with piezoelectric nanogenerators (PENGs) limit its use in energy harvesting.
  • This study introduces a method of cyclically switching direct current (DC) power terminals to align BaTiO nanoparticles in a PDMS matrix, resulting in improved piezoelectric performance in PENGs.
  • The aligned BaTiO PENGs demonstrated significantly higher output power (∼15 V and 1.91 μA) compared to randomly arranged composites, effectively powering six LEDs in series and highlighting the benefits of nanoparticle alignment in enhancing energy harvesting
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Background: Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments.

Methods: Using the TCGA data portal, we identified EHMT2 overexpression in GC samples.

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Myeloid cell leukemia 1 (Mcl-1) is a key regulator of the intrinsic apoptosis pathway. Overexpression of Mcl-1 is correlated with high tumor grade, poor survival, and both intrinsic and acquired resistance to cancer therapies. Herein, we disclose the structure-guided design of a small molecule Mcl-1 inhibitor, compound , that binds to Mcl-1 with subnanomolar affinity, inhibits growth in cell culture assays, and possesses low clearance in mouse and dog pharmacokinetic (PK) experiments.

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Antibiotic resistance rapidly develops against almost all available therapeutics. Therefore, searching for new antibiotics to overcome the problem of antibiotic resistance alone is insufficient. Given that antibiotic resistance can be driven by mutagenesis, an avenue for preventing it is the inhibition of mutagenic processes.

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The invasive species has inflicted significant economic losses in various European and Asian regions. To combat this pest, the parasitoid wasp has been effectively introduced in Europe. Despite its success, research on the field occurrence patterns of , particularly its phenology, remains scarce.

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Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions.

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Background & Aims: Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, how metabolic changes contribute to the progression of metaplasia to dysplasia remains unclear.

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Purpose: To investigate the prevalence of lower urinary tract symptoms/benign prostatic hyperplasia in a Korean population.

Materials And Methods: The Korean Prostate & Voiding Health Association provided free prostate-related community health care and conducted surveys in all regions of Korea from 2001 to 2022 with the cooperation of local government public health centers. A total of 72,068 males older than 50 were surveyed and analyzed.

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Weighting is a general and often-used method for statistical adjustment. Weighting has two objectives: first, to balance covariate distributions, and second, to ensure that the weights have minimal dispersion and thus produce a more stable estimator. A recent, increasingly common approach directly optimizes the weights toward these two objectives.

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-Acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is a zinc metallohydrolase that hydrolyzes -acyl-phosphatidylethanolamines (NAPEs) to form -acyl-ethanolamines (NAEs) and phosphatidic acid. Several lines of evidence suggest that reduced NAPE-PLD activity could contribute to cardiometabolic diseases. For instance, expression is reduced in human coronary arteries with unstable atherosclerotic lesions, defective efferocytosis is implicated in the enlargement of necrotic cores of these lesions, and NAPE-PLD products such as palmitoylethanolamide and oleoylethanolamide have been shown to enhance efferocytosis.

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Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation.

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-acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is a zinc metallohydrolase that hydrolyzes -acyl-phosphatidylethanolamine (NAPEs) to form -acyl-ethanolamides (NAEs) and phosphatidic acid. Several lines of evidence suggest that reduced NAPE-PLD activity could contribute to cardiometabolic diseases. For instance, expression is reduced in human coronary arteries with unstable atherosclerotic lesions, defective efferocytosis is implicated in the enlargement of necrotic cores of these lesions, and NAPE-PLD products such as palmitoylethanolamide and oleoylethanolamide have been shown to enhance efferocytosis.

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Background: In many research settings, the intervention implied by the average causal effect of a time-varying exposure is impractical or unrealistic, and we might instead prefer a more realistic target estimand. Instead of requiring all individuals to be always exposed versus unexposed, incremental effects quantify the impact of merely shifting each individual's probability of being exposed.

Methods: We demonstrate the estimation of incremental effects in the time-varying setting, using data from the Effects of Aspirin in Gestation and Reproduction trial, which assessed the effect of preconception low-dose aspirin on pregnancy outcomes.

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Rationale: Sedative-hypnotic drugs (SHDs) used for insomnia are recommended for short-term use owing to concerns regarding abuse and dependence. Nevertheless, drug discontinuation is challenging owing to rebound insomnia that occurs when the SHD is ceased. Therefore, a strategy is required to reduce or discontinue SHDs, while minimizing rebound insomnia.

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Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals.

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KCC2 is a K-Cl cotransporter that is expressed in neurons throughout the central nervous system. Deficits in KCC2 activity have been implicated in a variety of neurological disorders, including epilepsy, chronic pain, autism spectrum disorders, and Rett syndrome. Therefore, it has been hypothesized that pharmacological potentiation of KCC2 activity could provide a treatment for these disorders.

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Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed.

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A high-throughput cell-based screen identified redox-active small molecules that produce a period lengthening of the circadian rhythm. The strongest period lengthening phenotype was induced by a phenazine carboxamide (VU661). Comparison to two isomeric benzquinoline carboxamides (VU673 and VU164) shows the activity is associated with the redox modulating phenazine functionality.

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Imaging chromatin organization at the molecular-scale resolution remains an important endeavor in basic and translational research. Stochastic optical reconstruction microscopy (STORM) is a powerful superresolution imaging technique to visualize nanoscale molecular organization down to the resolution of ~20 to 30 nm. Despite the substantial progress in imaging chromatin organization in cells and model systems, its routine application on assessing pathological tissue remains limited.

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Introduction: Even if levodopa, dopamine agonists, and others are used for patients with Parkinson's disease, the effect is not sustained, and side effects such as motor fluctuation and dyskinesia are more likely to appear as the dose increases. Thus, new approaches for managing Parkinson's disease are needed. This study aimed to compare the metabolites and gut microbes between patients with Parkinson's disease and healthy individuals.

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Particulate matter (PM) can be categorized by particle size (PM, PM and PM), which is an important factor affecting the biological response. Exposure to PM in the air (dust, smoke, dirt and biological contaminants) is clearly associated with lung disease (lung cancer, pneumonia and asthma). Although PM primarily affects lung epithelial cells, the specific response of related cell types to PM remains to be elucidated.

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Article Synopsis
  • The human microbiome is crucial for immune function, digestion, and protecting against harmful bacteria, but its relationship with colorectal cancer (CRC) treatment is not fully understood.
  • This study found that propionate can inhibit CRC growth by promoting the breakdown of EHMT2, a protein that influences gene regulation tied to cancer.
  • The research suggests that combining propionate with an EHMT2 inhibitor may enhance treatment options for colon cancer, indicating potential new therapeutic strategies utilizing the microbiome.
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The lipid peroxidation product malondialdehyde and the DNA peroxidation product base-propenal react with dG to generate the exocyclic adduct, MdG. This mutagenic lesion has been found in human genomic and mitochondrial DNA. MdG in genomic DNA is enzymatically oxidized to 6-oxo-MdG, a lesion of currently unknown mutagenic potential.

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