Publications by authors named "H O Kim"

78,349 Publications

Multiple functions of pyruvate kinase M2 in various cell types.

J Cell Physiol 2021 Jul 26. Epub 2021 Jul 26.

Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Republic of Korea.

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30536DOI Listing
July 2021

Bioaerosol monitoring by integrating DC impedance microfluidic cytometer with wet-cyclone air sampler.

Biosens Bioelectron 2021 Jul 13;192:113499. Epub 2021 Jul 13.

Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

The recent outbreak of COVID-19 has highlighted the seriousness of airborne diseases and the need for a proper pathogen detection system. Compared to the ample amount of research on biological detection, work on integrated devices for air monitoring is rare. In this work, we integrated a wet-cyclone air sampler and a DC impedance microfluidic cytometer to build a cyclone-cytometer integrated air monitor (CCAM). The wet-cyclone air sampler sucks the air and concentrates the bioaerosols into 10 mL of aqueous solvent. After 5 min of air sampling, the bioaerosol-containing solution was conveyed to the microfluidic cytometer for detection. The device was tested with aerosolized microbeads, dust, and Escherichia coli (E. coli). CCAM is shown to differentiate particles from 0.96 to 2.95 μm with high accuracy. The wet cyclone air-sampler showed a 28.04% sampling efficiency, and the DC impedance cytometer showed 87.68% detection efficiency, giving a total of 24.59% overall CCAM efficiency. After validation of the device performance, CCAM was used to detect bacterial aerosols and their viability without any separate pretreatment step. Differentiation of dust, live E. coli, and dead E. coli was successfully performed by the addition of BacLight bacterial viability reagent in the sampling solvent. The usage could be further extended to detection of specific species with proper antibody fluorescent label. A promising strategy for aerosol detection is proposed through the constructive integration of a DC impedance microfluidic cytometer and a wet-cyclone air sampler.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2021.113499DOI Listing
July 2021

Increased telomere length in patients with frontotemporal dementia syndrome.

J Neurol Sci 2021 Jul 3;428:117565. Epub 2021 Jul 3.

Department of Neurology, Hanyang University College of Medicine, Gyeonggi-do, Republic of Korea.

Background: Telomeres are repetitive DNA sequences of TTAGGG at the ends of chromosomes. Many studies have shown that telomere shortening is associated with aging-related diseases, such as cardiovascular diseases, hypertension, diabetes, cancer, and various neurodegenerative diseases, including Alzheimer's disease, vascular dementia, Parkinson's disease, and dementia with Lewy bodies. However, changes in telomere length (TL) in patients with frontotemporal dementia (FTD) syndrome are unclear. Accordingly, in this study, we assessed TL in blood samples from patients with FTD syndrome.

Methods: Absolute TL was measured in peripheral blood leukocytes from 53 patients with FTD syndromes (25 with behavioral variant FTD, 19 with semantic variant primary progressive aphasia [PPA], six with nonfluent/agrammatic variant PPA, and three with amyotrophic lateral sclerosis [ALS] plus) and 28 cognitively unimpaired (CU) controls using terminal restriction fragment analysis.

Results: TL was significantly longer in the FTD group than in the CU group. All FTD subtypes had significantly longer TL than controls. There were no significant differences in TL among FTD syndromes. No significant correlations were found between TL and demographic factors in the FTD group.

Conclusions: Longer telomeres were associated with FTD syndrome, consistent with a recent report demonstrating that longer telomeres are related to ALS. Therefore, our results may support a shared biology between FTD and ALS. More studies with larger sample sizes are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2021.117565DOI Listing
July 2021

Blood First Assay Screening Trial (BFAST) in Treatment-Naïve Advanced or Metastatic Non-Small Cell Lung Cancer: Initial Results of the Phase 2 ALK-Positive Cohort.

J Thorac Oncol 2021 Jul 23. Epub 2021 Jul 23.

Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA. Electronic address:

Introduction: The Blood First Assay Screening Trial (BFAST) is an ongoing open-label, multi-cohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies/immunotherapy in treatment-naïve advanced/metastatic NSCLC. We present data from the ALK-positive cohort.

Methods: Patients aged ≥18 years with stage IIIB/IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT™) received alectinib 600 mg twice-daily. Asymptomatic/treated central nervous system (CNS) metastases were permitted. Primary endpoint: investigator-assessed objective response rate (ORR; RECIST v1.1). Secondary endpoints: independent review facility (IRF)-assessed ORR; duration of response (DoR), progression-free survival (PFS), and overall survival; safety. Exploratory endpoints: investigator-assessed ORR in patients with baseline CNS metastases; relationship between circulating biomarkers and response.

Results: In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of cases. Of these, 119 (5.4%) patients had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range = 2.6-18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5-93.5) by investigator and 92.0% (95% CI: 84.1-96.7) by IRF. Investigator-confirmed 12-month DoR was 75.9% (95% CI: 63.6-88.2). In 35 (40%) patients with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9-98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1-87.7). Safety data were consistent with the known tolerability profile of alectinib.

Conclusions: These results demonstrate the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2021.07.008DOI Listing
July 2021

INERTIA: A pilot study of the impact of progressive resistance training on blood pressure control in older adults with sarcopenia.

Contemp Clin Trials 2021 Jul 23:106516. Epub 2021 Jul 23.

University of Illinois at Chicago, Department of Medicine, 1747 W. Roosevelt Rd, Room 586 (MC 275), Chicago, IL 60608, United States. Electronic address:

Sarcopenia, and high blood pressure are highly prevalent, preventable conditions that pose significant burden for older adults and on the healthcare system. Current prevention and treatment of high blood pressure in sarcopenia, by non-pharmacological approaches remain limited and are far from optimal. Clinical trials and mechanistic studies provide encouraging evidence of a plausible therapeutic effect of progressive resistance training (PRT) on blood pressure in younger, and pre-hypertensive and hypertensive older adults. The impact of PRT on blood pressure has not been empirically tested in older adults with sarcopenia. This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full-scale randomized controlled trial that will determine the efficacy of PRT intervention as a therapeutic strategy for blood pressure control in older adults with sarcopenia. Participants (N = 90) will be randomized to receive exercise educational materials or the PRT intervention consisting of 24 supervised exercise sessions over 12-weeks. Follow-up assessments will occur at 12-weeks and one-year later. The primary outcome is systolic blood pressure and diastolic blood pressure, analyzed separately. Microvascular mechanisms linking muscle (perfusion, strength, function) to changes in blood pressure will be explored at baseline and 12-weeks. This study will provide new evidence for the therapeutic effect of PRT as a non-pharmacological strategy for improving blood pressure. Insights gained may also inform of the potential role of muscle strength as a novel target for blood pressure control, and future exercise prescription guidelines related to muscle strengthening in high-risk older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2021.106516DOI Listing
July 2021
-->