Publications by authors named "J Y Hong"

11,456 Publications

Assessing Clinical Outcomes in a Data-Rich World-A Reality Check on Real-World Data.

JAMA Netw Open 2021 Jul 1;4(7):e2117826. Epub 2021 Jul 1.

Bakar Computational Health Sciences Institute, University of California, San Francisco.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.17826DOI Listing
July 2021

Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease.

J Med Chem 2021 Jul 26. Epub 2021 Jul 26.

Department of Pharmaceutical Sciences, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536-0596, United States.

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 () effectively inhibits the catalytic activity of iP in ABCB1-overexpressing cells (IC: 105 nM) and has metabolic stability superior to its linear counterpart. DB-60 () also lowered the serum levels of IL-1α and ameliorated cognitive deficits in Tg2576 mice. The results collectively suggest that macrocyclic peptide epoxyketones have improved CNS drug properties than their linear counterparts and offer promising potential as an AD drug candidate.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00291DOI Listing
July 2021

Dissolving Candlelit Microneedle for Chronic Inflammatory Skin Diseases.

Adv Sci (Weinh) 2021 07 7;8(14):2004873. Epub 2021 May 7.

Department of Biotechnology Yonsei University 50 Yonsei-ro Seoul 03722 Republic of Korea.

Chronic inflammatory skin diseases (CISDs) negatively impact a large number of patients. Injection of triamcinolone acetonide (TA), an anti-inflammatory steroid drug, directly into the dermis of diseased skin using needle-syringe systems is a long-established procedure for treating recalcitrant lichenified lesions of CISDs, referred to as TA intralesional injection (TAILI). However, TAILI causes severe pain, causing patients to be stressed and reluctant to undergo treatment. Furthermore, the practitioner dependency on the amount and depth of the injected TA makes it difficult to predict the prognosis. Here, candle flame ("candlelit")-shaped TA-loaded dissolving microneedles (Candlelit-DMN) are designed and fabricated out of biocompatible and biodegradable molecules. Candlelit-DMN distributes TA evenly across human skin tissue. Conjoined with the applicator, Candlelit-DMN is efficiently inserted into human skin in a standardized manner, enabling TA to be delivered within the target layer. In an in vivo skin inflammation mouse model, Candlelit-DMN inserted with the applicator effectively alleviates inflammation by suppressing inflammatory cell infiltration and cytokine gene expression, to the same extent as TAILI. This Candlelit-DMN with the applicator arouses the interest of dermatologists, who prefer it to the current TAILI procedure.
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http://dx.doi.org/10.1002/advs.202004873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292898PMC
July 2021

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody.

Front Immunol 2021 8;12:701668. Epub 2021 Jul 8.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: We explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).

Methods: Among 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.

Results: We frequently observed hNLR in patients with SAR (53% 35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60] 1 [N = 76] 2 [N = 49]: 7.6 6.4 2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached 16.8 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).

Conclusions: We demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.
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http://dx.doi.org/10.3389/fimmu.2021.701668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298191PMC
July 2021

Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models.

Front Microbiol 2021 9;12:694897. Epub 2021 Jul 9.

National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea.

Recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. In this report, we performed deep sequencing for seed virus and SARS-CoV-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucleotide polymorphisms (SNPs) in SARS-CoV-2 by variant analysis. A total of 69 single-nucleotide variants (SNVs) were present in the 5'-untranslated region (UTR), 3'-UTR, , , , , and genes of the seed virus passaged in VERO cells. Between those present on the seed virus and those on each SARS-CoV-2 isolated from the lungs of the macaques, a total of 29 variants was identified in 4 coding proteins (ORF1ab, S, ORF3a, and N) and non-coding regions (5'- and 3'-UTR). Variant number was significantly different according to individuals and ranged from 2 to 11. Moreover, the average major frequency variation was identified in six sites between the cynomolgus monkeys and rhesus macaques. As with diverse SNPs in SARS-CoV-2, the values of viral titers in lungs were significantly different according to individuals and species. Our study first revealed that the genomes of SARS-CoV-2 differ according to individuals and species despite infection of the identical virus in non-human primates (NHPs). These results are important for the interpretation of longitudinal studies evaluating the evolution of the SARS-CoV-2 in human beings and development of new diagnostics, vaccine, and therapeutics targeting SARS-CoV-2.
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http://dx.doi.org/10.3389/fmicb.2021.694897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299785PMC
July 2021
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